AU679350B2

AU679350B2 - Arthropodicidal tetrahydropyrimidines

Info

Publication number: AU679350B2
Application number: AU19134/95A
Authority: AU
Inventors: Stephen Frederick Mccann
Original assignee: EI Du Pont de Nemours and Co
Current assignee: EIDP Inc
Priority date: 1994-02-09
Filing date: 1995-02-09
Publication date: 1997-06-26
Anticipated expiration: 2015-02-09
Also published as: AU1913495A; EP0743947A1; BR9506960A; HU9602186D0; CN1140452A; HUT76814A; MX9603273A; JPH09507676A; IL112577A0; PL315813A1; WO1995021846A1

Description

III C~ -I II I WO 95/21846 PCT/US95/01616 1

TITLE

ARTHROPODICIDAL TETRAHYDROPYRIMIDINES The present invention pertains to tetrahydropyrimidines which are useful as arthropodicides. U.S. 4,831,036 discloses insecticidal tetrahydropyrimidines that do not suggest those of the instant invention.

SUMMARY OF THE INVENTION This invention pertains to compounds of Formula I, including all geometric and stereoisomers, agriculturally suitable salts thereof, agricultural compositions containing them and their use to control arthropods in both agronomic and nonagronomic environments. The compounds are:

R

4

I

wherein X is selected from the group Si and Ge; A is selected from the group C 1

-C

20 alkylene, C 2

-C

20 alkenylene, C2-C 20 alkynylene, C 3

-C

8 cycloalkylene, C 7

-C

10 aralkylene and phenylene, each group optionally substituted with 1-3 substituents independently selected from W; or A is a direct bond;

R

1 and R 3 are independently selected from the group H, CI-CIO alkyl, C 2

-C

10 alkenyl or C 2

-C

10 alkynyl, each group optionally substituted with 1-2 substituents independently selected from the group halogen, CN, C(O)R 7

C(S)R

7

NO

2 OH, SC(O)R 7

SC(S)R

7

OC(O)R

7

OC(S)R

7

NR

8

C(O)R

7

NR

8

C(S)R

7 SH, Si(R 8

)(R

9

C

1

-C

4 alkoxy, C 1

-C

4 haloalkoxy, CI-C 4 alkylthio, CI-C 4 alkylamino, C 2

-C

8 dialkylamino, C 3

-C

8 cycloalkyl and phenyl optionally substituted with 1-3 substituents independently selected from W1; C 3

-C

8 cycloalkyl optionally substituted with 1-3 substituents independently selected from the group halogen, C 1

-C

2 alkyl and Cl-C 2 haloalkyl; C(O)R 1 1

C(S)R

11 phenyl optionally substituted with 1-3 substituents independently selected from W 1

CI-C

3 alkyl substituted with a 5- or 6-membered aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from W 1 and a 5- or 6-membered I I I WO 95/21846 PCTIUS95101616 2 aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-I1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from WI1;

R

2 is selected from the group H, C I-C 6 alkyl, C I-C 6 haloalkyl, C 2

-C

6 alkenyl,

C

2

-C

6 haloalkenyl, C2-C 6 alkynyl, C 2

-C

6 haloalkynyl, C 3

-C

7 cycloalkyl,

C

3

-C

7 halocycloalkyl and C 4

-C

7 cycloalkylakyl, each group optionally substituted with 1-3 substituents independently selected from W; or

R

2 and R 3 can be taken together as CH 2

CH

2 and CH 2

)CH

2

CH

2 each group optionally substituted with 1-2 CH 3

R

4 is selected from the group H and C 3

-C

6 trialkylsilyl; or R 4 is selected from the group C I-C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 I-C 10 alkoxy, C 1 I-C 10 alkylthio, phenyl, phenoxy, phenylthio and naphthyl, each group optionally substituted with 1-3 substituents; independently selected from W 1

R

5 and R 6 are independently selected from the group CI-CI 0 alkyl, C 2

-CI

0 alkenyl, C 2 -C 10 alkynyl, C 1 I-C 10 alkoxy, C I-C 10 alkylthio, phenyl, phenoxy, phenylthio and naphthyl, each group optionally substituted with 1-3 substituents independently selected from W I; OH; and C 3

-C

6 trialkylsilyl;

R

7 is selected from the group H, NH 2 OH, C I-C 6 alkyl, C I-C 6 haloalkyl, C I-C 6 alkoxy, C 1

-C

6 haloalkoxy, C 1

-C

6 alkylthio, C 1

-C

4 alkylamino, C2-C 8 dialkylainino and phenyl option'tly substituted with 1-3 substituents independently selected from WI;

R

8 is H; or R 8 is selected from the group C I-C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C I-C 10 alkoxy, phenoxy, phenyl and naphthyl, each group optionally substituted with 1-3 substituents independently selected from W I;

R

9 and R 10 are independently selected from the group C I-C 10 alkyl, C 2 -C 10 alcenyl, C 2 -C 10 alkynyl, C I-C 10 alkoxy, phenoxy, phenyl and naphthyl, each group optionally substituted with 1-3 substituents; independently selected from WI; and OH; R I is selected from the group H, NH 2 OH, C I-C 6 alkyl, CI -C 6 haloalkyl, C I-C 6 alkoxy, C I-C 6 haloalkoxy, C 1

I-C

2 alkylthio, C I-C 4 alkylamino, C 2

-C

8 dialkylamino and phenyl. optionally substituted with 1-3 substituents independently selected from WI; W is selected from the group halogen, CN, NO 2 OH, CI-C 6 alkyl, C 1

-C

6 haloalkyl, C 1

-C

6 alkoxy and CI-C 6 haloalkoxy; and WI is selected from the group halogen, CN, NO 2

CI-C

2 alkyl, C 1

-C

2 haloalkyl, C I-C 2 alkoxy, C I-C 2 haloalkoxy, C I-C 2 alkylthio, C I-C 2 haloalkylthio,

C

1

-C

2 alkylsulfonyl, CI-C 2 haloalkylsulfonyl, CI-C 4 alkylamino, C,-C 8 dialkylamino and C 3

-C

6 trialkylsilyl;,.

WO 95/21846 PCTIUS95/01616 3 Preferred Compounds A are compounds of Formula I wherein A is C

I

-C

6 alkylene;

R

1 is Cl-C 3 alkyl substituted with a 5- or 6-membered aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from W 1

R

4 is selected from the group CI-Clo alkyl and phenyl, each group optionally substituted with 1-3 substituents independently selected from W 1

R

5 and R 6 are independently selected from the group CI-C 10 alkyl and phenyl, each group optionally substituted with 1-3 substituents independently selected from W 1 and W1 is selected from the group halogen and C -C 2 haloalkyl.

Preferred Compounds B are compounds of Preferred A wherein X is Si;

R

1 is CH 2 substituted with pyridyl, thiazole or isoxazole, the ring optionally substituted with 1-2 halogen or 1-2 methyl;

R

2 and R 3 are taken together as CH 2

CH

2 or CH 2

CH

2

CH

2 each group optionally substituted with 1-2 CH 3 and

R

4

R

5 and R 6 are independently selected from CI-C 3 alkyl, C,-C 3 alkoxy and phenyl.

Preferred Compounds C are compounds of Preferred A wherein Xis Si;

R

1 is CH 2 substituted with pyridyl, thiazole or isoxazole, the ring optionally substituted with 1-2 halogen;

R

2 is selected from the group H and C 1

-C

3 alkyl; and

R

4

R

5 and R 6 are independently selected from CI-C 3 alkyl, C.IC 3 alkoxy and phenyl.

Specifically preferred for biological activity is Compound D of Preferred B which is: 1-[(6-chloro-3-pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-2-methyl-8-nitro- 6-[(trimethylsilyl)methyl]imidazo[1,2-c]pyrimidine.

Specifically preferred for biological activity is Compound E of Preferred B which is: 1-[(6-chloro-3-pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-8-nitro- 6-[(trimethylsilyl)methyl]imidazo[1 ,2-c]pyrimidine.

Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated C I I I WO 95/21846 PCTIUS95101616 4 from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate said stereoisomers. Accordingly, the present invention comprises racemic mixtures, individual stereoisomers, and optically active mixtures of compounds of Formula I as well as agriculturally suitable salts thereof.

The term or 6-membered aromatic ring" is defined as those rings which satisfy the Hiickel rule; examples include 5- or 6-membered monocyclic aromatic rings containing 0 to 4 heteroatoms such as phenyl, furyl, furazanyl, thienyl, pyrrolyl, pyrazolyl, oxazolyl, oxadiazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl isothiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and triazinyl with said ring attached through any available carbon or nitrogen. For example, when the aromatic ring is furyl, it can be 2-furyl or 3-furyl, for pyrrolyl, the aromatic ring is 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, for pyridyl, the aromatic ring is 2-pyridyl, 3-pyridyl or 4-pyridyl and similarly for other monocyclic aromatic rings.

In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" denotes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different isomers through C 1 0 Examples of "alkylene" include CH 2

CH

2

CH

2

CH

2

CH

2

CH

2 and the different isomers through C 20 "Alkenyl" denotes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different isomers through C 10 "Alkenyl" also denotes polyenes such as 1,3-hexadiene. Examples of "alkenylene" include CH=CH, CH2CH=CH,

CH=CHCH

2 and the different isomers through C 20 "Alkynyl" denotes straight-chain or branched alkynes such as emtynyl, 1-propynyl, 3-propynyl and the different isomers through C 1 0 Examples of "alkynylene" include C-C, CH 2 C=C, C=CCH 2 and the different isomers through C 20 "Alkoxy" denotes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different isomers through C 10 "Alkylthio" denotes straight-chain or branched alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfonyl" denotes

CH

3

S(O)

2 and CH 3

CH

2 S(0) 2 "Alkylamino" denotes methylamino, ethylamino, n-propylaniino, isopropylamino and the different butylamino isomers. "Dialkylamino" denotes nitrogen substituted with two alkyl groups, which may be different. Examples include N,N-dimethylamino and N-ethyl-N-methylamino. "Cycloalkyl" denotes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl and the different C 6 and C 7 isomers bonded to straight-chain or branched alkyl groups. The term "halogen", either alone or in compound words such as "haloalkyl", denotes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F 3 C, CICH 2

CF

3

CH

2 and CF 3 CC1 2 Examples of "haloalkenyl" include (C1) 2

C=CHCH

2 and c i ~dC-l~ II~ WO 95/21846 PCT/US95/01616

CF

3

CH

2

CH=CHCH

2 Examples of "haloalkynyl" include HC=CCHCI, CF 3

C=C,

CCI

3 CC and FCH 2

C=CCH

2 Examples of "haloalkoxy" include CF 3 O, CC1 3 CH2O,

CF

2

HCH

2

CH

2 0 and CF 3

CH

2 0. Examples of "haloalkylthio" include CCl 3 S, CF 3 S, and CC13CH 2 S. Examples of "haloalkylsulfonyl" include CF 3

SO

2 CC1 3

SO

2

CF

3

CH

2

SO

2 and CF 3

CF

2

SO

2 The total number of carbon atoms in a substituent group is indicated by the "Ci-Cj" prefix where i andj are numbers from 1 to 20. For example, C 1

-C

20 alkylene designates methylene, ethylene, and propylene through dodecylene isomers; C 2 alkoxy designates CH 3

CH

2 and C 3 alkoxy designates CH 3

CH

2

CH

2 0- or

(CH

3 2

CHO-.

DETAILS OF THE INVENTION The compounds of Formula I can be prepared by the reaction of Formula II compounds with one or more equivalents of an amine of Formula III and at least two molar equivalents of formaldehyde in a suitable solvent as depicted in Scheme 1. These reactions are typically carried out at temperatures ranging from 0 °C to the reflux temperature of the solvent, with 0 oC-25 °C being preferred. Scheme 1 reactions are typically complete within one day, however, certain Scheme 1 reactions may require longer reaction times (up to 5 days). Suitable solvents include alcohols such as methanol and ethanol, water, and polar aprotic solvents such as tetrahydrofuran and dimethylformamide. Formaldehyde can be used in amounts of about 2-10 molar equivalents.

Either solid paraformaldehyde or aqueous solutions of formaldehyde can be used. In some cases, it is desirable to use a small amount of a strong, non-oxidizing acid, such as hydrochloric acid, as a catalyst. Alternatively, a hydrohalide or a hydrosulfonic acid salt of amine m can be used.

Scheme 1 N02

R

RI N H H2N-A-X-R5

HCHO

I I R6

R

2

R

3 Compounds of Formula I can be prepared by reaction of compounds of Formula IV with an amine of Formula V as shown in Scheme 2. Typically, compounds of Formula IV are combined with 1-20 molar equivalents of an amine of Formula V in a suitable solvent at temperatures ranging from 0-100 Scheme 2 reactions typically require 6 to 48 h for completion, however longer reaction times may sometimes be required. Suitable solvents include but are not limited to, alcohols such as rethanol, ethanol and isopropanol; water; acetonitrile; dimethyl formamide and dimethyl acetamide. Amines of Formula V can also be used as hydrochloride salts; in these cases I I---I I~-mYL-- WO 95/21846 PCT/US95/01616 6 an equivalent amount of a base (such as sodium hydroxide) is added to the reaction mixtures.

Scheme 2

NO

2

RI

R2

R

3

NH

2 10 II X a suitable leaving group such as halogen, SCH 3 or OC 6

H

5 Alternatively, compounds of Formula II can be prepared by the reaction of Formula VI compounds with amines of Formula VII as depicted in Scheme 3 using conditions that are completely analogous to those described in Scheme 2.

Scheme 3

NO,

R3.

H

M

R

1

R

2 NH I IT

VII

Compounds of Formula IV can be prepared employing processes known in the art that involve reaction of nitroethene compounds of Formula VIII with amines of Formula VII (Scheme Compounds of Formula VI can be prepared by procedures which are analogous to those for compounds of Formula IV. Typical reaction conditions involve tih combination of equimolar amounts of compounds of Formulas VII and VIII in a suitable solvent or solvent mixture at temperatures in the range of about 0-100 °C.

Scheme 4 reactions typically require 6 to 48 h for completion. Suitable solvents typically have sufficient polarity to effect solution of compounds of Formulas VII and VIII, and include alcohols such as methanol, ethanol and isopropanol; ethers such as diethyl ether, tetrahydrofuran and dioxane; esters such as ethyl acetate; polar aprotic solvents such as dimethylformamide and dimethylacetamide; and water, as well as mixtures of solvents.

Scheme 4 N02XI

R

1

R

2 NH go IV VIII

V

i 1 i i I~ll WO 95/21846 PCT/US95/01616 7 Alternatively, compounds of Formula I can be prepared by the reaction of tetrahydropyrimidines of Formula IX with amines of Formula VII as depicted in Scheme 5 under conditions analogous to those described in Scheme 2. Preparation of compounds of Formula I by the reactions depicted in Scheme 5 are advantageous when either R 1 and/or R 2 are equal to H.

Scheme R4 02N A-X-R R6

RR

2 NH

I

X N)

I

R3 IX vI Compounds of Formula IX can be prepared by the reaction of Formula Il amines with compounds of Formula VI in the presence of formaldehyde as shown in Scheme 6 using procedures analogous to those described in Scheme 1.

Scheme 6

NO

2 R6

H

VI 1 Alternatively, as shown in Scheme 7, compounds of Formula I (where R 1 is other than H) can be prepared by the reaction of compounds of Formula I (where R 1 is H) with an alkylating agent of Formula X in the presence of a proton acceptor in a suitable solvent. Typical proton acceptors include NaH, KH, K 2 C0 3 NaHCO 3 and Cs 2

CO

3 and suitable solvents include DMF, THF, acetonitrile and water. In some cases, Scheme 7 reactions are carried out under phase transfer conditions using solvents that include toluene, dichloromethane, dichloroethane, ether, hexanes, benzene and the like and an aqueous base, including NaOH, KOH, NaHC0 3 Na 2

CO

3

K

2 C0 3 among others.

Typical phase transfer catalysts include tetrasubstituted ammonium halide salts, such as tetrabutylammonium iodide, benzyl triethyl ammonium bromide and the like. Reactions are typically carried out at temperatures ranging from 20-150 °C and are completed in 1 h to 3 days; however, 6 to 24 h is usually preferred.

i -F lpl llllslll~ I WO 95/21846 PCT/US95/01616 8 Scheme 7 R4

I

02Nr A-X R5 2 N X- 5 proton R| R6 R--X 2 aceptr (Rl is other NRIN than H) 2 IR3 I X2= a suitable leaving group

R

1 =H such as halogen, tosylate, methanesulfonate, or trifluoromethanesulfonate.

Alternatively, compounds of Formula I (where R 3 is other than H) can be prepared as shown in Scheme 8 using procedures that are completely analogous to those described for Scheme 7 reactions.

Scheme 8 R4

A-X-R

S R6 R3-X2 cceptor I (R 3 is other RI XN than H) 11 R2 H

XI

I

X

2 a suitable

R

3 H leaving group.

The formation of compounds of Formula II (where R 2 and R 3 are taken together to form a 5-or 6-membered ring and R 1 is other than H) is depicted in Scheme 9.

Conditions for carrying out Scheme 9 reactions are analogous to those described for Scheme 7.

Scheme 9 N0 2 NI proton NH RIX2 acceptor n(R is other SX than H) B X II X 2 is asuitable leaving group.

R =H B R 2 and R 3 taken together to forma 5- or 6- menbered ring.

-e s WO 95/21846 PCT/US95/01616 9 Alternatively, compounds of Formula II (where R 2 and R 3 are taken together to form a 5- or 6-membered ring) can be prepared as shown in Scheme 10. Typical reactions involve the combination of equimolar amounts of Formula XII and VIII compounds in a suitable solvent or solvent mixture at temperatures in the range of about 0-100 °C for a time ranging from 2 to 48 h. Suitable solvents typically have sufficient polarity to effect solution of Formula XII and VIII compounds and include alcohols such as methanol, ethanol and isopropanol; ethers such as diethyl ether, tetrahydrofuran and dioxane; esters such as ethyl acetate; polar aprotic solvents such as dimethylformamide and dimethylacetamide; and water, as well as mixtures of solvents.

Scherme

NO

2 R1--NH NH2N/ Rl N+ I (R 2 and R 3 taken together) B

X

1 X1 XII VIm B R 2 and R 3 taken together. X 1 =a suitable leaving group.

Diamines of Formula XII can be formed by reaction of Formula X compounds wth a stoichiometric excess of amines of Formula XIII as depicted in Scheme 11. Typical reactions involve the use of 1.5-10 equivalents of Formula Xm compounds in solvents such as methanol, ethanol, isopropanol, THF, water or acetonitrile, among others.

Scheme 11 reactions are sometimes carried out in the absence of solvent. Typical reaction times for Scheme 11 reactions range from 30 min to several days, with 6 to 24 h being generally preferred.

Scheme 11 RI X 2

H

2 N N XII

B

X Xll

X

2 a suitable B=R 2 and R 3 leaving group. taken together.

Alternatively, Formula XII diamines where B is an optionally substituted CH 2

CH

2 group can be prepared by the two-step procedure depicted in Scheme 12. In Step i of Scheme 12, amines of Formula XIV are treated with potassium cyanide and compounds of Formula XV in the presence of zero to three equivalents of acid to form aminonitriles of Formula XVI. One skilled in the art will recognize that compounds of Formula XV i ~P I WO 95/21846 PCT/US95/01616 can be formaldehyde, acetaldehyde or acetone. Other cyanide salts as well as HCN can be used in the procedure as well as hydrohalide and other acid salts of Formula XIV.

Suitable solvents include methanol, ethanol, isopropanol and water, as well as combinations of solvents. Scheme 12 reactions are usually complete with 24 h.

Alternative procedures for the preparation of amino nitriles such as XVI can be found in the literature (see, Synth. Commun., (1985), 15, 157; Synthesis, (1979), 127).

In Step ii of Scheme 12, aminonitriles of Formula XVI are reduced to form diamines of Formula XII. This reduction can usually be achieved using lithium aluminum hydride or borane in amounts ranging from 0.75 to 3 molar equivalents, in a solvent such as diethyl ether or THF. Reactions are carried out at temperatures ranging from -20 °C to the reflux temperature of the solvent for times ranging from 0.5 h to 2 days.

Alternatively, the reduction of compounds of Formula XVI to compounds of Formula XII can be achieved using catalytic hydrogenation over a catalyst such as palladium on carbon or Raney nickel. The addition of ammonia to the hydrogenation reaction is sometimes useful to maximize the yield of diamines of Formula XII.

Scheme 12 Step i

RI--NH

2

R

12 R3C(0) KCN HN CN H+ R 12R2X R13 XIV XV XVI R2 and R 13 are independently H or CH 3 Step ii XVI 2 (R 12 andR 13 are RI2 independently H or CH 3 R13

XII

An alternative procedure for the preparation of diamines of Formula XII where B is an optionally substituted CH 2

CH

2 group is depicted in Scheme 13. In Step i of Scheme 13, amino amides of Formula XVII are treated with 1 to 2 molar equivalents of acid chlorides of Formula XVIII in the presence of 1 to 3 molar equivalents of a base such as NaOH, KOH, K 2

CO

3 NaHC0 3 pyridine or triethylamine. Suitable solvents include THF, CH 2 Cl 2 water or pyridine. The products (compounds of Formula XIX) can be isolated by extraction or, more conveniently, by removal of solvent, and are usually suitable for use in Step ii of Scheme 13 in crude form. Amides of Formula XVII can be used either in neutral form as depicted or as the salt form (typically as the HCI or I WO 95/21846 PCTIUS95/01616 11

CF

3

CO

2 H salt, among others). When the salt form of XVII i J, an additional one equivalent of base is used in Step i of Scheme 13.

In Step ii of Scheme 13, the amide of Formula XIX is converted to the diamine of Formula XII by treatment with a reducing agent such as LiAlH 4 BH3-THF or BH3-SMe 2 in a solvent such as THF or Et 2 O at temperatures ranging from 0 °C to the reflux temperature of the solvent. Typical reaction times range from 0.5 h to 2 days.

Analogous procedures are well-known in the literature (see Synthesis, (1981), 441).

When R 12 is CH 3 and R 13 is H, then XVII is alanine amide. The use of either the D- or the L- form of alanine amide of Formula XVII or its salt provides a convenient means of obtaining enantiomerically enriched forms of diamines of Formula XII. When compounds of Formula II are prepared as described for Scheme 10 reactions using enantiomerically enriched forms of compounds of Formula XII, the compounds of Formula II are obtained in enantiomerically enriched form. When compounds of Formula I are prepared as described for Scheme 1 reactions using enantiomerically enriched forms of compounds of Formula II, the compounds of Formula I are obtained in enantiomerically enriched form.

Scheme 13 Step i 0

H

2 N ,C(

O

)NH2 base RI14N C(0)NH RI2>(RI3 RR 4 C(O) -R1 XVII XVm XIX Step ii

[H]

XX XII

R

14

CH

3

SCH

2 3-pyridyl, 6choro-3-pyridyl, or 5,6-dichloro-3-pyridyl.

Alternatively, diamines of Formula XII can be obtained in enantiomerically enriched forms by resolution with enantiomeric acids, such as tartaric acid. Such resolutions are well-known to one skilled in the art (see Synthesis, (1991), 789 for a related example).

Amines of Formula I can be prepared by the reaction of a silyl halide or germanyl halide of Formula XX with an excess of ammonia as shown in Scheme 14. These transformations typically involve the addition of compounds of Formula XX to anhydrous, liquid ammonia (2 to 100 equivalents) at temperatures ranging from -78 to I_ L~ WO 95/21846 PCT/US95/01616 12 100 OC. In cases where temperatures greater than -33 °C are required, the reactions are carried out in a sealed, high pressure apparatus. Usually no solvent is required; however, solvents such as THF or diethyl ether are sometimes used. Reactions generally require h to 72 h for completion. Typical work-up procedures usually involve the evaporation of excess ammonia, precipitation of ammonium halide by addition of ether, and removal of solvent. One skilled in the art will recognize that there are many alternative methods for converting halides of Formula XX to primary amines of Formula II. References for a variety of procedures can be found in March, Adv. Org.

Chem., 4th Ed., pp 1276-7.

Scheme 14 R6 I NH 3 X2-A-X-R m

I

R4

XX

X

2 is a suitable leaving group.

Silanes and germanes of Formula XX can be prepared by the reaction of organolithium or Grignard reagents of Formula XXI with chlorosilanes or chlorogermanes of Formula XXII as depicted in Scheme 15. These reactions typically involve the mixture of equimolar amounts of compounds of Formulas XXI and XXII in organic solvents such as pentane, hexane, THF, ether and the like at temperatures ranging from -78 to 25 °C for times typically ranging from 2 h to 4 days.

Scheme R6

I

R

4 -M X- A-X-a

XX

R

XXI XXII M i, MgCI, X 2 is a suitable MgBrorMgI. leaving group.

Chlorosilanes and chlorogremanes of Formula XXII can be prepared by treatment of dichlorides of Formula XXIII with one molar equivalent of an organometallic reagent of Formula XXIV as depicted in Scheme 16. Conditions for Scheme 16 reactions are analogous to those described for Scheme 15 reactions. The preparation of compounds a WO 95/21846 PCTIUS95/01616 13 of Formula XX where R 4 is equal to R 5 can be achieved by the use of two equivalents of compounds of Formula XXIV in procedures depicted in Scheme 16.

Schenr, 16

X

2

R

5 -M xi

XXIII

XNXIV

X

2 is as suitable leaving group.

M 1,MgQ], MgBrorMgl.

Compounds of Formula XX where R 4

R

5 and R 6 are identical can be prepared by the reaction of trichiorides of Formula XXV with three equivalents of organometallic compounds of Formula)XXIV as shown in Scheme 17. Conditions for Scheme 17 reactions are analogous to those described for Scheme 15 reactions.

Scheme 17

X

2 A-Xa 3 3R 5 -M -~XX (R 4

=R

5

R

6 xxv XXIV

X

2 =a suitable leaving group.

M U, MgQ1, MgBr or MgI Compounds of Formula XX where R 4 is an alkoxy or phenoxy group can be prepared by the reaction of an alcohol or phenol of Formula XXVI with a chiorosilane or chiorogermane, of Formula XXII in the presence of a base such as triethylamine, pyridine or Nail as depicted in Scheme 18.

Scheffr 18 RI 5 0H XXOM XX (10=alkoxy orphenoxy) xxVI RI 5 C, -CIO aI or C 6

H

WO 95/21846 PCTI/US95/01616i 14 Procedures for the formation of ethers XX (R 4 is alkoxy or phenoxy) are well-known to one skilled in the art (see, Org. Synth., 69, 96; J. Chem. Soc. Chem.

Commun. (1988) 802; J. Organomet. Chem., (1970), 22, 599.) Silanes and germanes of Formula XX where R 4 and R 5 are alkoxy or phenoxy can be prepared by the reaction of dichlorides of Formula XXIII with two equivalents of alcohols of Formula XXVI in the presence of a base using procedures analogous to those described for Scheme 18 reactions. Similarly, compounds of Formula XX where R 4

R

and R 6 are alkoxy or phenoxy can be prepared by the reaction of trichlorosilanes or trichlorogermanes of Formula XXV with three equivalents of an alcohol of Formula XXVI In the presence of a base using procedures analogous to those described for Scheme 18 reactions.

One skilled in the art will recognize that a wide variety of alternative procedures for the preparation of compounds of Formulae XX, XXII, XXIII and XXV are known in the art. Leading references concerning silanes include, Fleming, Organosilicon Chemistry, in Comprehensive Organic Chemistry, (1979), 3, 541; Colvin, Silicon in Organic Synthesis, Butterworths, Boston, (1981); and Pawlenko, Organosilicon Chemistry, Walter de Gruyter, New York, (1986). Leading references for germanes include, Rivibre, et, al., Germanium, In Comprehensive Organometallic Chemistry, (1982), 2, 399; Lesbre, et. al, The Organic Compounds of Germanium, Wiley, London, (1971).

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences into the synthesis will aid in obtaining the desired products. The use and choice of the protecting group will be apparent to one skilled in chemical synthesis.

EXAMPLE 1 Step A: Methyl N-[(6-chloro-3-pyridinyl)carbonyll-alanine A solution of 50.5 g (0.29 mol) of 6-chloronicotinyl chloride and 290 mL of

CH

2 C12 was added to a solution of 60 g (0.43 mol) of DL-alanine methyl ester hydrochloride and 290 mL of saturated aqueous sodium bicarbonate solution. Then, mL of aliquat 336 (Aldrich) was added and the resulting two-phase mixture was stirred rapidly at 25 0 C for 24 h. The resulting mixture was partitioned between CH 2

CI

2 and saturated NaHC0 3 The aqueous layer was extracted with three portions of CH 2 C2.

The combined organics were washed twice with saturated NaHCOI, dried over MgSO 4 and concentrated to give 56.1 g of the title compound as a viscous yellow oil. 1 H NMR (300 MHz, CDC1 3 8 8.82 (d,J=2.4Hz,lH), 8.10 (dd,lH), 7.41 7.10 (br d,lH), 4.78 (quintet,1H), 3.80 1.53 (d,3H).

Ir ir I_ ~R WO 95/21846 PCT/US95/01616 Step B: 6-Chloro-N-[ 1 -(aminocarbonvl)-ethyll-3-pyridine carboxamide A solution of 50.5 g (0.21 mol) of the product from Step A and 150 mL of anhydrous MeOH was added to 575 mL of 15% anhydrous ammonia in anhydrous methanol. The resulting solution was stirred at room temperature for 48 h. The solid product was removed by filtration, washed with ethanol and dried under vacuum to give 43.5 g of the title compound as a white solid; m.p. >220 1 H NMR (400 MHz,

(CH

3 2 SO-d 6 6 8.87 (apparent s,lH), 8.79 8.29 7.65 7.45 (br s,lH), 7.03 (br s,lH), 4.41 (quintet,lH), 1.33 (d,3H).

Step C: N 2 -[(6-chloro-3-pyridinyl)-methyl]-1,2-propanediamine Borane-methyl sulfide complex (18.7 mL, 0.19 mol) was added dropwise to a mechanically stirred mixture of 8.5 g (0.04 mol) of the product from Step B and 112 mL of THF at 50-60°C. The resulting orange-yellow suspension was refluxed for 2 h, cooled to room temperature and quenched by the careful dropwise addition of 62 mL of 6 N HC1. The resulting pale yellow mixture was stirred at room temperature for 24 h and then was washed with three portions of ether. The aqueous layer was basified with mL of 50% NaOH (added with cooling) and extracted with 3 x 150 mL of 2:1 methylene chloride-chloroform solution. Combined organic layers were dried (K 2

CO

3 and concentrated to give 3.5 g of the title compound as a yellow oil. 1 H NMR (400 MHz,CDCl 3 6 8.33 (apparent s,lH), 7.69 7.30 3.78 (ABq,2H), 2.75 2.63 (dd,lH), 2.53 (dd,1H), ca. 1.50 (br s,3H); 1.07 (d,3H).

Step D: 2-Chloro-5-r[5-methyl-2-(nitromethylene)- -imidazolidinvllmethyllpyridine A suspension of 2.5 g (0.013 mol) of the product from Step C, 1.6 g (0.009 mol) of 1,l-bis(methylthio)-2-nitroethylene and 63 mL of anhydrous EtOH was heated at reflux for 3 h and was then allowed to stand at 24 0 C for 72 h. The resulting mixture was concentrated and chromatographed on silica gel using 15:1:0.1 CH 2

CI

2

NH

4 0H to give 0.70 g of the title compound as a yellow solid; m.p. 127-131 0

C.

IH NMR (400 MHz,CDCl 3 8 8.70 (br s,lH), 8.27 7.56 7.35 (d,1H), 6.56 4.33 (ABq,2H), 3.95-3.85 3.45-3.35 1.33 (d,3H).

Step E: 1-r(6-Chloro-3-pyridinvl)methvll-1.2.3.5.6.7-hexahvdro-2-methvl-8-nitro-6r(trimethvlsilyl)methvllimidazo[ 1.2-c]pyrimidine (Compound 1) A mixture of 0.5 g (1.9 mmol) of the product from Step D, 0.31 mL (4.1 mmol) of 37% aqueous formaldehyde, 0.21 g (2.1 mmol) of trimethylsilyl methylamine and 4 mL of ethanol was stirred at room temperature for 18 h. The resulting mixture was concentrated and the yellow residue was triturated with diethyl ether and filtered to give 0.32 g of the title compound as a yellow solid, m.p. 112-115 oC. 1 H NMR (300 MHz,CDC13) 6 8.30 7.81 7.30 5.04 (1/2ABq,lH), 3.98-3.68 3.23 (dd,HI), 1.94 1.26 0.08 (s,9H).

i i WO 95/21846 PCTIUS95/01616 16 EXAMPLE 2 Step A: 2-Nitromethylene-imidazolidine A suspension of 1,l-bis(methylthio)-2-nitroethylene (125 g, 0.76 mol), ethylenediamine (50.6 mL, 0.76 mol) and ethanol (757 mL) was heated at reflex for 4 h.

The resulting mixture was cooled to 5°C and filtered. The solids were washed with cold ethanol and dried under vacuum to yield 102.5 g of a tan solid. 1 H NMR (200 MHz, Me 2 SO-d 6 5 8.27 (br s,2H), 6.33 3.58 (s,4H).

Step B: 1,2.3.5.6.7-Hexahvdro-8-nitro-6-[(trimethylsilvl)methyl1imidazorl .2-clpyrimidine A suspension of 0.98 g (7.6 mmol) of the product from Step A, 1.26 mL (16.7 mmol) of 37% aqueous formaldehyde and 15 mL of ethanol was treated with 1.11 mL (8.3 mmol) of trimethylsilyl methylamine at room temperature. After 18 h, the resulting solution was concentrated to give 1.85 g of a yellow solid. 1 H NMR (400 MHz,CDC13) 8 8.33 (br s,lH), 4.00 3.80 (overlapping t, 2H and s,2H), 3.66 2.14 0.10 (s,9H).

Step C: 1-1(6-Chloro-3-pyridinyl)methyll- 1.2.35,6,7-hexahydro-8-nitro-6- [(trimethylsilyl)methyl-imidazo[ .2-c]pyrimidine A mixture of 0.5 g (2.0 mmol) of the product from Step B, 0.8 g (3.9 mmol) of 6chloro-3-chloromethyl-pyridine hydrochloride, 0.004 g (0.1 mmol) of tetra-n-butyl ammonium iodide, 6.4 mL of 50% aqueous KOH and 8.4 mL of methylene chloride was stirred vigorously for 24h. The resulting mixture was poured into water and extracted with 3 portions of methylene chloride. The combined organic layers were washed with saturated aqueous sodium bicarbonate, dried (K 2

CO

3 and concentrated. The crude product was triturated with diethyl ether and filtered to give 0.34 g of the title compound as a yellow solid, m.p. 145.5-147.0 C. 1H NMR (400 MHz,CDC13) 6 8.35 7.90 (dd,lH), 7.33 4.86 3.90 3.77 3.68-3.55 2.02 0.10 (s,9H).

By the general procedures described herein, or obvious modifications thereof, the compounds of Tables 1-16 and Index Tables A-D can be prepared. The compounds of Table 1, line 1 can be referred to as 1-1, 1-2, 1-3 and 1-4 (as designated by line and column). All the other specific compounds covered in these Tables can be designated in an analogous fashion. In Tables 1-16 and Index Tables A-D, the following notations have been used: i PCTIUS$95101616 WO 95/21846 a-P mPhp-Ph- 0o 0 Me CH 3 Et CH 2

CH

3 n-Pr (CH 2 2

CH

3 i-Pr CH(CH 3 2 n-Bu (CH 2 3

CH

3 i-Bu CH 2

CH(CH

3 2 s-Bu CH(CH 3

)CH

2

CH

3 t-Bu C(CH 3 3 Ac C(O)CH 3 n-pentyl (CH 2 4

CH

3 n-hexyI (CH 2 5

CH

3 c -Pr= c-Bu C-Pentyl c-hexyl =0 (CH2) 2 Ne 3 1 CH 2

CH

2 NMe 3 1

CH

2 (2-Cl-Ph) =1

CH

2 (4-Cl-Ph) CH 2-ci 2-pyr 0 O 3-pyr =0 4-pyr 0 2-CH 2 -pyr H-0 3-CH 2 -pyr N N Ci 2-CH 2 -6-al-pyr 3-H -6C -p r CH2a N a 6--3-pyr =0 6-F-3-pyr E1

F

CH23-aPh)= WO 95/21846 WO 9521846PCTIUS951016l6 6-Br-3-pyr 6-Me-3-pyr 6-OMe-3-pyr 3C 2 0 E 0Me aQOMe a-1N

N

2 a N F

CH

2 N Br

C

2 N Me N e r=

I

C

2

CH

2 al 'yr Q

C

3-CH 2 -6-F-pyr 2 &6Br-riyr 3-CH 2 -6Me-pyr 3-CH 2 -6-OMe-py, 2-CH 2 -3-Me-pyrazyl Me 2-C,-S-Me-pyrazyl QI

M

C'12,- (Me 2-CH 2 -6-Me-pyrazyl

Q

C2NY 2-CH 2 -5--pyzy Q 3-CH 2 -pyridazyl CH 2

N-N

3-CH 2 -6-a-pyridazy] CH 2 (3)

N

2-CH 2 -pyrindyl CH 2 0D 4-CH 2 -pyrinidyl CH 2 (3)N 5- C H -p y ini yl C M 2 7

N

5-Ci2pyiridl 0>2 -Me

N

5-CH 2 -2-M-pyrndyl CH2Q >m ,s CH2 2 thiazolyl 2-ai 2 -pymzyl WO 95/21846 5-Oi-2-Me- thiazolyl 2 -2-Cl- thiazolyl 2 -2-Br- thiazolyl 2-01H2- thienyl 2-CH 2 -5-Br-thienyl- 2.'H 2 -furYl 2-CH 2 -2-pyirolyl 54CH 2 -3-Me-isommzly] S CH 2 Cl s

CI

Br-

N

a12--'

S

C12' Q Br 0 CH2-

H

PCTfUS9S/01616 al

\N

0H 5-GH 2 -3-CQ-isoxazolyl 2 -3-Br-isoxazolyl 42-adiazyra 5-e2-thiadiazlyl 2-CH 2 -tiniadiazlyl=

N-N

Me

NHIN

'Al ~s M Table I

QN

RI-N""

RI=

~Z~i 12 COLUMN 31

H

Me Et n-Pr i-Pr n-Bu Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

C

2

CH

2 Ne 3 l

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-Cl-pyr WO 95/21946 WO 95/ 1846PCTIUS95/01616 s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-QMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr 2-CH 2 -pyr 3-CH 2 -Pyr 4-CH 2 -Pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thi enyl 3-CH 2 -pyrazolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CHi 2 -6-CF 3 -pyr 3-CH 2 -6-QCF 3 -Pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -pyrimidyl

CH

2 (2-CI-Ph)

CH

2 (3-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -Pyrrolyl 3-CH 2 -1I-Me-pyrazolyl 4.-CH 2 -1-Me-pyrazolyl 5-CH 2 -1-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH2)-5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -Pyridazy] 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl 4-C11 2 -pyriniidyl 5-CH 2 -2-Me-pyriMdyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-C11 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-Cl-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 1-Me-pyrrolyl 3-CH 2 -1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-Cl-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-Cl-isoxazolyl 5-CH 2 -3-Br-isoxazolyl I L WO 95/21846 WO 95/1846 CTfUS95/01616 21 Table 2

R=

COLUMN

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu C-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -PyrazolYl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-Cl-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-Cf1 2 -5-CF 3 -thienyl

NCCH

2

CH

2

ACNHCH',

AcNHCH 2

CH

2

CH

2 NMe 3 l

C

2

CH

2 Ne 3 l

CH

2 (2-CI-Ph)

CH

2 (3-Cl-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH-

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -Pyrrolyl 3-CH 2 -1-Me-pyrazolyl 4-CH 2 1-Me-pyrazolyl 5-CH 2 1-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH-,-6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-Cl-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-Cl-pyr 2-CH 2 -5,6-di-C1-pyr 3-CH 2 3-CH 2 -4-Cl-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1-Me-pyrroly! 3-CH 2 -1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-CI-pyrim*idyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl WO 95/21846 WO 95/ 1846PCr[US9S/01616 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-C l-4-ovr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -Pyrimidyl 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 5-CI-2-thiadiazy] 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CHZ-3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl Table 3 0 2 N K~"SiMe 3 .Ii 2 COLUMN I_ 4

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-Cl-thienyl 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3

I

CH

2 (2-CI-Ph)

CH

2 (3-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

C

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyr-rolyl 3-CH 2 -pyrrolyl 3-CH 2 -1I-Me-pyrazolyl 4-CH 2 1-Me-,pyrazolyl

CH-

2 (3,4-d-i-CI-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr

.CH

2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,.6-di-CI-pyr 4-CH 2 -2,6-di-Cl-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

CH

2

C

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 E-t 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 1-Me-pyrrolyl WO 95/21846 WO 9521846PCTtUS95/O 1616 6-Br-3-pyr 6-F- 3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidy) 2-CH 2 -pyrimidyl 5-CH2-1I-Me-pyrazolyl 2-Ci!h-pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2.CH 2 -5-Me-pyrazy! 2-CH 2 -6-Me-pyrazyl 3-.CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-Ci-pyridazyl 4-CH 2 -Pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 3-CH 2 -1 -Me-pyrrolyl 5-CH2)-thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-CI-pyfimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-CI-2-thiadiazyi 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl I L I Table 4 02N SiMe 3

R

1 11.

N

H

3

C'-

R=

COLUMN

1 2 ::T3 1

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH{

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH,2-isoxazolyl M(1 2

NCH

2

C

2 (c-Bu) 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2 (2NI-Ph

CH

2 (2-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH-

2

CH

2

CHCH

2

C

2 (3,4-diCl-Ph) 2-CH 2 -6-CI-Pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6.CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-Cl-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr WO 95/21846 WO 9521846PCTUS9S/01616 3-pyr 4..pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5.CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-ovr

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazoly] 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -PYraZOlYl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-Cl-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-QMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -pyrimidyl MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-QMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -PyffOlyl 3-CH 2 1-Me-pyrazolyl 4-CH 2 -1I-Me-pyrazolyl 5-CH 2 -1 -M.--pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI..pyridazy] 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2 r.H 2 EtINCH 2

CH

2 Me 9

)NCH

2

)CH

2 2-CH 2 -1I-Me-pyrrolyl 3-CH 2 1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-Cl-pyfimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-Cl-isoxazolyl 5-CH2)-3-Br-isoxazolyl Table 0 2 N i We 3

RII

ii 2 1 4 Ph

CI-

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH2CH 2

CH

2 (3,4-di-Ci-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 WO 95/21846 WO 9521846PCT1JS95101616 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 n-Bu s-Bu i-Bu c-Pr

H-CCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-'2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2 012(c-Bu)

C

2 (c-pentyI)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH2-2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 7pyrazolyl 4-CH 2 -pyrazoly] 5-CH 2 -pyrazolyl 2-CH 2 -5-Cl-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-QMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrim-idyl 2-CH 2 -pyrimidyl

CH

2

CH

2 )NMe, 3

I

CH

2 (2-CI-Ph)

CH

2 (3-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH',

TH2CHCH 2 MeSCH 2

CH

2 ACSCH-,CH2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 -1-Me-pyrazolyl 4-CH 2 -1 -Me-pyrazolyl 5-CH 2 -1-Me-pyrazolyl 2-CH2-pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl 4-CH 2 7pyrimidy1 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-diienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 2-CH 2 -4-Cl-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-Cl-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2 CHCHiCH 2

C

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 1 -Me-pyrrolyl 3-CH 2 1-Me.-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-CI-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazy] 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl

I

L WO 95/21846 PCT[US95/01616 26 Table 6

CH

3 3 2 ~COLUMN 4_ 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 19 t.

197 198 199 200 201 202 203 204 205 206 207 208 209

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br.2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

C

2 (c-Bu)

CH

2 (c-pentyl)

C

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -Pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2

ACNHCH

2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CR

2

CH

2 NMe 3

I

CH

2 (2-CI-Ph)

C

2 (3-CIPh)

CH

2 (4-CI-Ph)

C

2 CMe)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -Pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 -1lMe-pyazolyl 4-CH 2 1-Me-pyrazolyl 5-CH 2 -1-Me-pyrazolyl 2-CH 2 -Pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyra-.yl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl

CH

2 (3,4-di-CI-Ph) 2-CH 2 -&-CL-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-Cl-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CHZ-2-CI-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1-Me-pyrrolyl 3-CH 2 -1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH4 2 -2-CI-pyrimidyl 2-CH 2 Cl-pyrazyl 2-CH 2 -6&OCF 3 -pyr 2-CH4 2 -thiadiazy] 5-.Me-2-thiadiazyl WO 95/21846 WO 9521846PCTUS95/01616 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 )-6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -Pyrimidyl 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl ,5-CH 2 -3-Me-isoxazolyl 5-CH 2 )-3-F-is oxazolyl 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl Table 7 02N N' SMe 3

RI.

CH

3

RI

11 2 1 3 I4

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph 2CH 2 -Pr 3-CH 2 -pyr 4-CH 2 -Pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazoly]

S-CH

2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -Pyrazolyl 5-CH 2 7pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3

I

CH

2 (2-CI-Ph)

CH

2 (3-Cl-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 -1-Me-pyrazolyl 4-CH 2 1-Me-pyrazolyl Cl 2 (3,4-di-Cl-Ph) 2-CH 2 -6CI-pyr 3-CH 2 -6-Cl-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CHZ-5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-Cl-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-Cl-thiazolyl CH4 2

CHCH

2

CH

2

CH

2 C(Me)CH 2 CH2)

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1-Me-pyrrolyl WO 95121846 WO 9521846PCTIUS95/01616 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-ipvr 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-O~le-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimiddyl 2-CH 2 -pyrimidyl 5-CH 2 1-Me-pyrazoly] 2-CH 2 -PYraz]l 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl 4-CH 2 -pyrimaidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 3-CH- 2 1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-Cl-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazy] 5-Me-2-thiad~azyl 5-C1-2-thiad~azyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl Table 8 0 2 NS~e

CH

3

K

CH

3 COLUMN I2 1 2 4

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl) 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3 l

CH

2 (2-CI-Ph)

CH

2 (3-Cl-Ph)

CH

2 Cl-Ph)

CH

2 C(Me,)CH 2

HCCCH

2

CH

2

C

2

CHCH

2 MeSCH 2

CH

2 2CH 2 ,--C-Pyr 3-CH 2 -6-Cl-jpyr 4-CH 2 -6-Cl-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -4-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-Cl-pyr 3-CH4 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr WO 95/21846 WO 9521846PCTIUS95/01616 4-pyr

ACSCH

2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-Cl-2-pyr 6-CI-3-pyr 6-CI-4-pyr

CH

2 (c-hexyl) 5-CHZ-2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -PylazOlyl 5-CH 2 -Pyrazolyl 2-CH 2 -5-Cl-thienyl 2-CH 2 -5-Me-thienyl 3-CI- 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6--Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -pyrimidyl AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -Pyrrolyl 3-CH 2 -Pyrrolyl 3-CH 2 -1I-Me-pyrazolyvl 4-CH 2 -1 -Me-pyrazolyl 5-CH 2 -1I-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazy] 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazy] 4-CH 2 -pyrimi dyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

)CH

2

CH

2 C(Me)CH 2 CH2

CH

3

CHCHCH

2

CH

3

CHCHCH

2 CHi Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1-Me-pyrrolyl 3-CH 2 -1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thieny'l 5-CH 2 -2-CI-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-CI-2-thiadiazyl 5-CFZ-2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl.

Table 9 C' N~SiMe 3 2=

H

Me Et n-Pr i-Pr n-Bu Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

C

2 (c-pr) 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH- 2 AcNH-CH 2 CH2

CH

2 NMe 3

I

C

2

CH

2 Ne 3

I

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr WO 95/21846 WO 9521846PCT/US95/01616 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 .316 317 318 319 320 321 322 323 324 s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Mve-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

C

2 (chexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyimidyl 2-CH 2 -pyriniidyl

CH

2 (2-CI-Ph)

CH

2 (3-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2

ACSCH

2 CH4 2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -Pyrrolyl 3-CH 2 -1 -Me-pyrazolyl 4-CH 2 -1-Me-pyrazolyl 5-CI-1 2 -l-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -Pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -&-CI-pyridazyl 4-CH 2 -Pyrirnidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 ;-thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CEICH

2

CH

2

CH

2 C(Me)CH,2CH 2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2 NCH9CH 2 Me 2 NCfl-1CH 2 2-CH 2 -1I-M(--pynfolyI 3-CH 2 -1-MC.-PyrrolyI 5-CH 2 -thiaz DIYI 2-CH 2 -thienyl 5-CH 2 -2-CI-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazy] 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-Cl-isoxazolyl 5-CH 2 -3-Br-isoxazolyl

I

Table 0 2 N Nr'K SiWe 3

H

3

C,:

H

R

3 WO 95/21846 WO 9521846PCTIUS95/01616 R3 S~~~~COLUMN 32 1 3 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr &-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-pyr Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -Pyr 5-CH 2 -isoxazolyl Me2NCH 2

CH

2 (c-pentyl)

C

2 (chexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyr-azolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 1 )-5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CHZ-6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -Pyrimidyl 2-CH 2 -pyrin-ddyl 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2

ACNHCH

2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3

I

CH

2 (2-CI-Ph)

C

2 (3-Cl-Ph)

C

2 (4-Cl-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -Pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 -1 -Me-pyrzolyl 4-CH 2 -1I-Me-pyrazolyl 5-CH 2 -1I-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Mt-pyrazy] 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH2-5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

C

2

CHCH

2

CH

2

C.H

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1I-Me-Pyrrolyl 3-CU 2 I -Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-CI-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazy] 5-Me-2-thiadiazyl 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 -5-C1-thiadiazyl 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl WO 95/21846 WO 95/ 1846PCTIUS95/01616 32 Table I11 0 2 N SiMe 3 H

RZ

3 I~i [2COLUMN 1 [3 4_

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-CI-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr Ph

C

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph C11 2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH-,-5-Me-thi enyl 3-CH 2 -pyrazolyl 4-CH 2 -PyrazOlYl 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-ppr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3

I

CH

2 (2-CI-Ph)

CH

2 (3-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

C

2

CHCH

2 MeSCH 2

CH

2 AcSCH2)CH 2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -PYrrOlYl 3-CH 2 -1 -Me-pyrazolyl 4-CH 2 -1 -Me-pyrazolyl 5-CH 2 1-Me-Pyrazly' 2-CH 2 -Pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyiidazyl 4-CH 2 -Pyrimidyl

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-Cl-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-CI-pyr 2-CH 2 2-CH 2 -4-Cl-pyr 2-CH 2 -3-Cl-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-Cl-pyr 3-CH 2 -,2-Cl-pyr 3-CH 2 -5.6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -I-Me-pyrrolyl 3-CH 2 1-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-Cl-pyfimi dyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazyl 5-Cl-2-thiadiazyl WO 951846CTIUS95/01616 WO 95/21846 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-Cl-2-pyr 6-CI-3-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -PYrimidyl 2-CH 2 -PYrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyi 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-r--isoxazolyl 5-CF 2 -2-thiadiazy] 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl Table 12 N~SiMe3

H

3

C,,

Cf! 3

R

3

R

3 COLUMN I 2 3_ 114

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr A-pyr AcSCH 2 Et 2

NCH

2 c-Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Bu)

C

2 (c-pentyl) CI1 2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -pyrazolyl 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CHZ-5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3 l

CH

2

CH

2 NMe 3

I

C

2 (2-Cl-Ph)

CH

2 (3-CI-Ph)

C

2 (4-Cl-Ph)

C

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-Cl-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 1-Me-pyrazolyl 4-CH 2 -1I-Me-pyrazolyl 5-CH 2 1-Me-pyrazolyl 2-CH 2 -Pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazy]

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-Cl-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-Cl-pyr 2-CH 2 2-CH 2 -4-Cl-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CHI-5,6-di-CI-pyr 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-Cl-i.iazolyl

CH

2 CHCH2CA'2

C

2 C(Me)CH 2

CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 -1-Me-PYrrOlYl 3-CH 2 -1 Me-pyrrolyl 5-CH 2 -thiazolyl 2-CfH 2 -thieaiyl 5-CH 2 -2-Cl-pyrin-ddyl WO 95/21846 WO 9521846PCTIUS95/01616 422 423 424 425 426 427 428 429 430 431 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI-4-ovr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-C11 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -Pyrimidyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazyl 4-CH 2 -Pyrimidyl 5-CH2-2-Me-pyrimiddyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 )-thiadiazyl 5-Me-2-thiadiazy] 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazyl 2-CH 2 2-CH 2 5-CH 2 -3-Ci-isoxazo]l 5-CH 2 -3-Br-isoxazolyl Table 13 0N N SiMe 3

CH

3

R

3 COLUMN_ 2II J3

H

Me Et n-Pr i-Pr n-Bu s-Ru i-Ru c-Pr

HCCCH

2

NCCH

2 2-pyr 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-Ru c-pentyl c-hexyl Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 7pyr 3-CH 2 -pyr 4-CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (c-Ru)

C

2 (cpentyl)

C

2 (chexyI) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -Pyrazolyl 4-CH 2 -pyrazolyl 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2

ACNHCH

2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3

I

CH

2 (3-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

C

2

CHCH

2 MeSCH 2

CH

2 AcSCH 2

CH

2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -Pyrrolyl 3-CH 2 -Pyrrolyl

CH

2 (3,4-di-CI-Ph) 2-CH 2 -6-CI-pyr 3-CH 2 -6-CI-pyr 4-CH 2 -6-Cl-pyr 2-CH 2 2-CH 2 -4-CI-pyr 2-CH 2 -3-CI-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CH 2 -4-CI-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr 4-CH 2 -2.6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl

CH

2

CHCH

2

CH

2

CH

2 C(Me)CH 2

CH-,

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH,)

Et 2

NCH

2

CH.,

WO 95/21846 PTU9/11 PCTfUS95/01616 6-F-2-pyr 6-Me-3-pyr 6-Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-Cl-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-Cl-2-pyr 6-Cl-3-pyr 6-CI-4-pyr 5-CH 2 -pyrazolyl 2-CH 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CH 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 76-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -pyrimidyl 3-CH 2 1-Me-pyrazolyl 4-CH 2 1-Me-pyrazolyl 5-CH 2 -1I-Me-pyrazolyl 2-CH 2 -Pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazy] 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazyl 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-C1-pyridazyl 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thieriyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl Me 2

NCH

2

CH

2 2-CH 2 -I -Me-pyrrolyl 3-CH 2 -1 -Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH2)-thienyl 5-CH 2 -2-Cl-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazy] 5-Cl-2-thiadiazyl 5-CF 2 -2-thiadiazy] 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl Table 14 0 2 N N'SiWe 3

H

3 cK- :x CH 3

R

3 COLUMNj 1 2 T 3

H

Me Et n-Pr i-Pr n-Bu s-Bu i-Bu c-Pr

HCCCH

2

NCCH

2 2-pyr Ph

CH

2 Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph

CH

2 (c-Pr) 2-CH 2 -Pyr 3-CH 2 -pyr 4.CH 2 -pyr 5-CH 2 -isoxazolyl Me 2

NCH

2

CH

2 (C-Bu) 2-CH 2 -5-CF 3 -thienyl

NCCH

2

CH

2 AcNHCH 2 AcNHCH 2

CH

2

CH

2 NMe 3

I

CH

2

CH

2 NMe 3 l

CH

2 (2-CI-Ph)

CH

2 (4-CI-Ph)

CH

2 C(Me)CH 2

HCCCH

2

CH

2

CH

2

CHCH

2

CH

2 ,-i-Cl-Pyr 3-CH- 2 -6-Cl-pyr 4-CH 2 -6-Cl-pyr 2-CH 2 2-CH 2 -4-Cl-pyr 2-CH 2 -3-Cl-pyr 2-CH 2 -5,6-di-CI-pyr 3-CH 2 3-CU 2 -4-Cl-pyr 3-CH 2 -2-CI-pyr 3-CH 2 -5,6-di-CI-pyr WO 95/21846 WO 9521846PCTfUS95/01616 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 3-pyr 4-pyr AcSCH 2 Et 2

NCH

2 c-.Bu c-pentyl c-hexyl 6-F-2-pyr 6-Me-3-pyr 6.Br-3-pyr 6-F-3-pyr 6-OMe-3-pyr 6-Me-2-pyr 6-Br-2-pyr 5-CI-2-pyr 5-Me-2-pyr 5-Br-2-pyr 5-F-2-pyr 6-OMe-2-pyr 2-thiadiazolyl MeSCH 2 6-CI-2-pyr 6-CI-3-pyr 6-CI.4-pyr

CH

2 (c-pentyl)

CH

2 (c-hexyl) 5-CH 2 -2-Me-thiazolyl 5-CH 2 -2-Br-thiazolyl 2-CH 2 -5-Me-thienyl 3-CH 2 -pyrazolyl 4-CH 2 -Pyrazo,'yl 5-CH 2 -Pyrazolyl 2-CH- 2 -5-CI-thienyl 2-CH 2 -5-Me-thienyl 3-CH 2 -6-Me-pyr 3-CH 2 -6-OMe-pyr 3-CH 2 -6-Br-pyr 2-CH 2 -6-CF 3 -pyr 3-CH 2 -6-F-pyr 3-CI1 2 -6-CF 3 -pyr 3-CH 2 -6-OCF 3 -pyr 2-CH 2 -6-Me-pyr 2-CH 2 -6-OMe-pyr 2-CH 2 -6-Br-pyr 2-CH 2 -6-F-pyr 5-CH 2 -pyrimidyl 2-CH 2 -pyrimidyl MeSCH 2

CH

2 AcSCHICH 2 2-CH 2 -furyl 5,6-di-CI-3-pyr 5-OMe-2-pyr 2-CH 2 -pyrrolyl 3-CH 2 -pyrrolyl 3-CH 2 -1I-Me-pyrazolyl 1 -Me-pyrazolyl 5-CH 2 1-Me-pyrazolyl 2-CH 2 -pyrazlyl 2-CH 2 -3-Me-pyrazlyl 2-CH 2 -5-Me-pyrazyl 2-CH 2 -6-Me-pyrazyl 3-CH 2 -pyridazy] 3-CH 2 -6-Me-pyridazyl 3-CH 2 -6-CI-pyridazy] 4-CH 2 -pyrimidyl 5-CH 2 -2-Me-pyrimidyl 2-CH 2 -5-CF 3 -thiadiazyl 2-CH 2 -5-Br-thienyl 5-CH 2 -3-Me-isoxazolyl 5-CH 2 -3-F-isoxazolyl 4-CH 2 -2,6-di-CI-pyr 5-CH 2 -2-CI-thiazolyl CHnCHCH 2

CH,)

C'

2 C(Me)CH 2

)CH

2

CH

3

CHCHCH

2

CH

3

CHCHCH

2

CH

2 Et 2

NCH

2

CH

2 Me 2

NCH

2

CH

2 2-CH 2 1-Me-pyrrolyl 3-CH- 2 -1I-Me-pyrrolyl 5-CH 2 -thiazolyl 2-CH 2 -thienyl 5-CH 2 -2-CI-pyrimidyl 2-CH 2 2-CH 2 -6-OCF 3 -pyr 2-CH 2 -thiadiazyl 5-Me-2-thiadiazy] 5-CI-2-thiadiazyl 5-CF 2 -2-thiadiazy] 2-CH 2 2-CH 2 5-CH 2 -3-CI-isoxazolyl 5-CH 2 -3-Br-isoxazolyl 1 L I The following additional notations have been used to represent various embodiments of Q in Tables 15 and 16: Q-1 6-C1-3-pyridyl, Q-2 5,6-dichloro-3-pyridyl, Q-3= Q-4 3-chloro-5-isoxazolyl and Q-5 CH 3

SCH

2 Table 0 2

NI

k 2

R

3 WO 95/21846 PcTJUS95/01616 37

COLUMN

1 2 3 4 505 A=direct band; R 2

R

3 =Me; R 4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 506 A=direct bond; R 2

R

3 =Me; R 4 =t-Bu; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 507 A=direct bond; R 2

R

3 -Me; R4-Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 508 A=direct bond; R 2

R

3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 509 A=direct bond; R 2

R

3

R

4 =t-Bu; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 510 A=direct bond; R 2

R

3

R

4 =Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 511 A=CH 2

R

2

R

3 -Me; R 4 =t-Bu; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 512 A=CH 2

R

2

R

3

R

4 =Ph; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 513 A--CH 2

R

2

R

3 -Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 514 A=CH 2

R

2

R

3 =Me; R 4 =t-Bu; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 QA 515 A--CH 2

R

2

R

3 =Me; R$-Ph; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 516 A--CH 2

R

2

R

3 -Me; R 4 =Et; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 517 A=Cfl 2

R

2

R

3 -Me; R 4

CH

2 CH; R 5 =Me; R 6 =Me; Q-1 (Q-2 Q-3 Q-4 518 A--CH 2

R

2

R

3 =Me; R 4

=CH

2

CHCH

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 519 A=CH 2

R

2

R

3 =Me; R 4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 512 A=CH 2

R

2

R

3 =Me; R 4 =i-PrO; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 513 A--CH 2

R

2

R

3 -Me; R 4 =EtO; R 5 -Eto; R 6 =Me; Q-1 Q-2 Q-3 Q-4 514 A=-CH 2

R

2

=H;,R

3 =Me; R -i-PrO; R 5 =i-ThrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 515 A=CH 2

R

2

R

3 =Me; R 4 -EtO; R 5 =EtO; R 6 -=EtO; Q-1 Q-2 Q-3 Q-4 516 A--CH 2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =i-PrO; R 6 -i-PrO; Q-1 Q-2 Q-3 Q.-4 517 A=-CH 2

R

2

R

3 -Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 518 A=CH 2

R

2

R

3 -Me; R 4

R

5 -Et; R 6 -Et; Q-1 Q-2 Q-3 Q-4 519 A=-CH 2

CH

2

R

2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 520 A=(CH 2 3

R

2

R

3 -Me; 1$-Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 521 A--CH 2 CHCH; R 2

R

3 =Me; R 4 -Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 522 A--CH 2 CC& R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 523 A=CH 2

CH

2 CHCH; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 524 A=-CH 2

CH

2 CC; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 525 A=o-Ph; R* 2

R

3 -Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 526 A~m-Ph; R 2

R

3 -Me; R$=Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 527 A=p-Ph; R 2

R

3 =Me; R 4 =Mle; Rb-Me; p 6 -Me, Q-1I Q-2 Q-3 Q-4 528 A~direct bond; R 2 =Me;

R

4 =Me; R 5 =Me; R 6 =Me, Q-1 Q-2 Q-3 Q-4 529 A=direct bond; R 2 =Me; R 3 =Me; R 4

R

5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 530 A=direct bond; R 2 =Me; R 3 =Me; R 4

R

5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 531 A=direct bond; R 2 =Me; R 3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 WO 95121846 PCTIUS95/01616 38 532 A=direct bond; R 2 =Me; R 3 =Me. R 4

R

5

R

6 Q-1 Q-2 Q-3 Q-4 533 A=direct bond; R 2 =Me; R 3 =Me; R 4 -Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 534 A=direct bond;, R 2

R

3 =Me; R 4 =Me; R 5 =Ph; R 6 Ph; Q.1 Q-2 Q-3 Q-4 535 A=CH 2

R

2

R

3

R

4 =Me; R 5

R

6 Q-i Q-2 Q-3 Q-4 536 A--CH 2

R

2 -Me; R 3

R

4 =Me; R 5

R

6 Q-1 Q-2 Q-3 Q-4 537 A=-CH 2

R

2 =Me, R 3 =Or: R4W-3u; R 5 =Me; R 6 =Me; Q-1 Q-.2 Q-~3 Q-4 538 A=-CH 2 RL-Me; R 3 =ile: R'"Ii R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 539 A=-CH 2

R

2 Me; R 3 =Me; R 4 -i-Pr; R 5 =i-Pr; R 6 =i-pr; Q-1 Q-2 Q-3 Q-4 540 A=-CH 2

R

2 =Me; R 3 =Me; R 4

R

5 =Ph; R 6 =ph; Q-1 Q-2 Q-3 Q-4 541 A=-CH 2

R

2 -Me; R 3 -Me; R 4 =Ph; R 5 =Ph; R 6 Q.1 Q-2 Q-3 Q-4 542 A--CH 2

R

2 =Me; R 3 =Me; R 4 =Et; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 543 A--CH 2 R2ZMe: R 3 =Me; R 4

=-CH

2 CH,; R 5

R

6 Q-1 Q-2 Q-3 Q-4 544 A=-CH 2

R

2 =Me; R 3

R

4

-CH

2

CHCH

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 545 A=-CH 2

R

2

R

3

R

4 =EtO;, R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 546 A=-CH 2

R

2 =Me; R 3 r.

4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 547 A--CH 2

R

2 =Me, R 3 =Me; R 4 =EtO; R 5 =EtO; R 6 Q-1 Q-2 Q-3 Q-4 548 A=-CH 2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =i-PrO; R 6 Q-1 Q-2 Q-3 Q-4 549 A=-CH 2

R

2 =Me; R 3 =Mc; R 4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 550 A--CH 2

R

2 -Me; R 3 -Me; R 4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 551 A=-CH 2

R

2 Me; R 3 =Me; R 4 =MeO; R 5 =MeO; R 6 Q-1 Q-2 Q-3 Q4 552 A=-CH 2

R

2 =Me; R 3 =Me; R 4 =MeO; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 553 A=-CH 2

R

2 =Me; R 3 =Me- R 4

R

5 =Me; R 6 =Me; Q- 1 Q-2 Q-3 Q-.4 554 A=-CH 2

R

2 =Me; R 3

R

4

R

5

R

6 Q-1 Q-2 Q-3 Q-4 555 A=-CH 2

CH

2

R

2 =Me; R 3 =Me; R 4 =Me; R 5 -Me; R 6 Me; Q-1 Q-2 Q-3 Q-4 556 A--(CH2) 3

R

2 =Me; R 3 =Me; R 4

R

5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 557 A=-CH 2 CHCH; R 2 =Me; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-.3 QA 558 A--CH 2 CC; R 2 =Me; R 3 =Me: R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 559 A=-CH 2

CH

2 CHCH; R 2 =Me; R 3

R

4 =Me, R 5

R

6 =Me; Q-1 Q-2 Q-3 Q 4 560 A=-CH 2

CH

2 CC; R 2

R

3 =Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 561 A=o-Ph,; R 2

R

3 =Me, R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 562 A=m-Ph;, R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 563 A=p-Ph; R 2 =Me; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q.4 564 A=-CH 2

R

2

R

3 -Me; R 4 =MeQ; R 5 =MeQ; R 6 =MeO-; Q-1 Q-2 Q-3 Q-4 565 A--CH 2

R

2

R

3 =Me; R 4 =MeO; R 5 =MeO; R 6 Q-1 Q-2 Q-3 Q-4 566 A--CH 2

R

2

R

3 =Me; R 4 =MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 567 A=direct bond; R 2

R

3 =Me; R 4 =Me, R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 568 A=direct bond; R 2 =Et; R 3 =Mc' R 4 =t-Bu; R 5 =Me; R 6 =Me; Q-1 Q-2 'Q-3 Q4 569 A-direct bond; R 2

R

3 =Me; R 4

R

5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 WO 95/21846 pCTlus9s/o16l6 39 570 A=direct bond;, R 2 Et; R 3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 571 A=direct bond; R 2

R

3 =Me; R 4 =t-BU; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 572 A=direct bond; R 2 -Et; R 3

R

4 =Ph; R 5 =Ph; R 6 =Ph, Q-1 Q-2 Q-3 Q-4 573 A=direct bond; R 2 =Et; R 3 -Me; R 4 -Me; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 574 A--CH 2

R

2

R

3 =Me; R 4 =Me; R 5

R

6 =Ph; Q-1 Q-2 Q-3 Q-4 575 A--CH 2

R

2 Et; R 3 -Me; R 4 -t-Bu; R 5 =Me: R 6 Q-1 Q-2 Q-3 Q.4 576 A=-CH 2

R

2 =Et; R 3 =Me; R 4 =Ph; R 5 =Me* R 6 -Me; Q-1 Q-2 Q-3 Q-4 577 A=-CH 2

R

2

R

3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 578 A--CH 2

R

2 =Et; R 3 =Me; R 4 =t-Bu; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-.3 Q-4 579 A=-CH 2

R

2

R

3 =Me; R 4 Ph; R 5

R

6 =Ph; Q-1 Q-2 Q-3 Q-4 580 A--CH 2

R

2 =Et; R 3 =Me; R 4 -Et; R 5 -Me; R 6 Q-1 Q-2 Q-3 Q-4 581 A--CH 2 R2=Et; R 3 =Me; R 4

=-CH

2 CH; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 582 A--CH 2

R

2 =Et; R 3 =Me; R 4

=CH

2

CHCH

2

R

5 =Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 583 A=-CH 2

R

2 =Et; R 3 =Me; R 4 =EtO; R 5 =Me; R 6 =Me; Q-.1 Q-2 Q-3 Q-4 584 A=-CH 2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 585 A--CH 2

R

2 Et; R 3 =lMe; R 4 =EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 586 A=-CH 2

R

2 =Et; R 3 Me; R 4 =i-PrO; R 5 =i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 587 A=CH 2

R

2 -Et; R 3 -Me; R 4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 588 A--CH 2

R

2 =Et; R 3 =Me; R 4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 589 A=-CH 2

R

2 =Et; R 3 =Me; R 4 =MeO; R 5 =MeO; R 6 Q-1 Q-2 Q-3 Q-4 590 A-=CH 2

R

2

R

3 =Me; R 4 =MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 591 A=CH 2

R

2 =Et; R 3 =Me; R 4

R

5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 592 A=-CH 2

R

2

R

3 =Me; R 4 5 E;R=t Q-1 Q-2 Q-3 Q-4 593 A=-CH 2

CH

2

R

2 -Et; 3 =Me; R 4 =Me; R 5 =Me; R 6 Me; Q-.1 Q-2 Q-3 Q-4 594 A=(CH 2 3

R

2

R

3 =Me; R 4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 595 A=-CH 2 CHCH; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 596 A--CH 2 CC; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-I Q-2 Q-3 Q-4 597 A--CH 2

CH

2 CHCH; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 598 A--CfH 2

CH

2 CC; R 2 =Et; R 3 -Me; R 4 -Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 599 At-o-Ph; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q.-2 Q-3 Q-4 600 A=m-Ph, R 2 -Et; R 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 601 Amp-Ph;, R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-.1 Q-2 Q-3 Q-4 602 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 603 A=direct bond; R 2

+R

3

=-CH

2

CH

2 Rd;4--Bu; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 604 A=direct bond; R 2

+R

3

-CH

2

CH

2

R

4

R

5 =Me; R 6 =me; Q-1 Q-2 Q-3 Q-4 605 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4

R

5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 606 A-direct bond; R 2

+R

3

=-CH

2

CH

2

R

4 =t-Bu; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q4 607 A-direct bond; R 2

+R

3

-CH

2

CH

2

R

4 =Ph; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 WO095/21846 PCT(US9S101616 608 Adirect bond; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 609 A-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 610 A=CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =t-Bu; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 611 A=-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

R

5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 612 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 613 A--CH 2

R

2

+R

3

-CH

2

CH

2

R

4

R

5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 614 A--CH 2

R

2

+R

3

=-CH

2 CF1 2

R

4

R

5 -Ph; R 6 Q-1 Q-2 Q-3 Q-4 615 A-CH 2

R

2

+R

3

-CH

2

CH

2

R

4 =Et; R 5 -Me, R 6 -Me; Q-1 Q-2 Q-3 Q-.4 616 A--CH 2

R

2 -iR 3

=-CH

2

CH

2

R

4

-CH

2 CH; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 617 A-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

CH

2

CHCH

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3' Q-4 618 A-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =EtQ; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 619 A=-CH 2

R

2

+R

3

=-CH

2

CH

2 7; R 4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 620 A=-CH 2

R

2

+R

3

=-CH

2 CHi 2

R

4 =-EtO; R 5 =EtQ; R 6 =Me; Q-1 Q-2 Q-3 Q-4 621 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =i-PrO; R 5 =i-PrO; R 6 Q-1 Q-2 Q-3 Q-4 622 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 =EtQ; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 623 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =MeO; R 5 =MeO; R 6 =MeQ; Q-1 Q-2 Q-3 Q-4 624 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 -MeQ; R 5 =MeO;, R 6 Q-1 Q-2 Q-3 Q-4 625 A=H 2

R

2

R

3

-C

2

C

2

-;R

4 Me; 5 6 =e;Q-1 Q-2 Q-3 Q4 Q-5 626 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =He; R 5 =Me; R 6 =Me 627 A--CH 2

R

2

-+R

3

=-CH

2

CH

2

R

4

R

5 Met; R 6 Met; Q-1 Q-2 Q-3 Q-4 628 A-C

H

2H 2

R

2

+R

3

-CC

H

2- R 4

R

5 R R 6 e; Q-1 Q-2 Q-3 Q-4 629 A=(CH2 C3

R

2

+R

3

-CH

2

CH

2

R

4 =Me; R 5 =Me, R 6 =Me; Q-1 Q-2 Q-3 Q-4 630 A=(CH 2 CHC; R 2

+R

3

-CH

2

CH

2

R

4 Me; R 5 Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 631 A--CH 2 CC; R 2

+R

3

-CH

2

CH

2

R

4 =Me R 5 =Me R 6 =Me; Q-1 Q-2 Q-3 Q-4 632 A--HC;R=3=

CH;R

2

+R

3

-C

2

CH

2 R=Me; R6=Me; Q-1 Q-2 Q-3 Q-4

R

6 =me; 633 A=CH 2

CH

2 CC; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 634 A=o-Ph; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 635 A=m-Ph; R 2

+R

3

=-CH

2

CH

2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 636 A-p.Ph; R 2

+R

3

=-CH

2

CH

2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q.3 Q.4 637 A=direct bond; R 2

+R

3 =-CH(Me)CH2-;

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 638 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 =t-Bu; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 639 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 =Ph; R 5 =Me; R 6 Me; Q-1 Q-2 Q-3 Q-4 640 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 =i-Pr; R 5 =i-Pr; Q-1 Q-2 Q-3 Q-4

R

6 =i-Pr; 641 A=direct 'bond;, R 2

+R

3 =-CH(Me)CH 2

R

4 =t-Bu; R 5 -Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 642 A=direct bond,, R 2

+R

3 -CH(Me)CH2-;

R

4 =Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 WO 95/21846 PCT[US9S/01616 41 643 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 -Me; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 644 A-CH 2

R

2

+R

3 CH(Me)CH 2

R

4 =Me; R 5 =Ph; R 6 Ph; Q-1 Q-2 Q-3 Q-4 645 A-CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -t-Bu; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 646 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =Ph; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 647 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-Pr; R 5 =i-Pr; R 6 Q-1 Q-2 Q-3 Q-4 648 A=CH 2

R

2

+R

3

R

4 =t-Bu; R 5 =Ph, R 6 =Ph; Q-1 Q-2 Q-3 Q-4 649 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =Ph; R 5 =Ph; R 6 =Ph; Q-1 Q.-2 Q-3 Q-4 650 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =Et; R 5 =Me; R 6 =Me, Q-1 Q-2 Q-3 Q-4 651 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

-CI-

2 CH; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 652 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

CH

2

CHCH

2

R

5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 653 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -Eto; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 654 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 655 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO;, R 5 =EtO; R 6 =Me, Q-1 Q-2 Q-3 Q-4 656 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-PrO; R 5 =i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 657 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtQ; R 5 =EtO: R 6 =EtO; Q-1 Q-2 Q-3 Q-4 658 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =MeO; R 6 =-MeO; Q-1 Q-2 Q-3 Q-4 659 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =MeO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 660 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 661 A-CH 2

R

2

+R

3 =-CH-(Me)CH 2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 662 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

R

5 =rEt; R 6 Et; Q-1 Q-2 Q-3 Q-4 663 A--CH 2

CH

2

R

2

+R

3 =-CH(Me)CH2-;

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 664 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 665 A--CH 2 CHCH, R 2

+R

3 =-CH(Me)CH 2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 666 A--CH 2 CC; R 2

+R

3 =-CH(Me)CH2-;

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 667 A=CH 2

CH

2 CHCH; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 668 A--CH 2

CH

2 CC; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 669 A=o-Ph; R 2

+R

3 =-CH(Me)CH2-;,

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 670 A=m-Ph; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 671 A=p-Ph; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 672 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 673 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =iPr; R 5 =iPr; R 6 =iPr; Q-1 Q-2 Q-3 Q-4 674 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 675 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =tBu; R 5 =Me; R 6 =Me; Q-1 Q.-2 Q-3 Q-4 676 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =Eto; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 677 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 WO 95/21846 PCTIUS95/01616 42 678 A=(CH 2 3

R

2

-+R

3

-CH

2

CH

2

R

4 -EtO, R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 679 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 680 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =n-PrO; R 5 =n-PrO; R 6 Q-1 Q-2 Q-3 Q-4 PrO; 681 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =i-PrO; R 5 =i-PrO; R 6 =i-PrO; Q-1 Q-2 Q-3 Q-4 682 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =Et; R 5 =Et; R 6 =Et; Q-1I Q-2 Q-3 Q-4 683 A=(CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -iPr; R 5 -iPr; R 6 =iPr; Q-1 Q-2 Q-3 Q-4 684 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 -Ph; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 685 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 -tBu; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 686 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 -EtO; R 5 -EtO; R 6 =-EtO; Q-1 Q-2 Q-3 Q-4 687 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4

R

5 =MeO; Q-1 Q-2 Q-3 Q-4

R

6 =MeO; 688 A--(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =Eto; R 5 =EtO; R 6 Q-1 Q-2 Q-3 Q-4 689 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 690 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =-n-PrO; R 5 =n-PrO; R 6 Q-1 Q-2 Q-3 Q-4 PrO; 691 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =-PrO; R 5 =-PrO; R 6 Q-1 Q-2 Q-3 Q-4 PrO; 692 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 693 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =EtQ; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 694 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =MeO; R 5 -MeO;, R 6 =MeO; Q-1 Q-2 Q-3 Q-4 695 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 696 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH 2

R

4 =Et; R 5

R

6 =Et; Q-1 Q-2 Q-3 Q-4 697 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO; R 5 =EtO; R 6 =-EtO; Q-1 Q-2 Q-3 Q-4 698 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH2-;

R

4 =MeQ; R 5 =MeO; Q-1 Q-2 Q-3 Q-4

R

6 =MeO; 699 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 700 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Me; R 5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 701 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =t-Bu; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 702 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Ph; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 703 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr. Q-1 Q-2 Q-3 Q-4 704 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =t-Bu; R 5

R

6 =Ph; Q-1 Q-2 Q-3 Q-4 705 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Ph; R 5 =Ph; R 6 =Ph: Q-1 Q-2 Q-3 Q-4 706 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Et; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 707 A-CH 2

R

2

+R

3

=-(CH

2 3

R

4

=-CH

2 CH; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 708 A--CH 2

R

2

+R

3

=-(CH

2

R

4

=-CH

2

CHCH

2

R

5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 709 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =EtO; R 5

R

6 =Me; Q-1 Q-2' Q-3 Q-4 710 A=CH 2

R

2

+R

3

=-(CH

2

R

4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 m WO095/21846 PC'r/Us95I01616 43 711 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =EtQ;, R 5 =EtO; R 6 =Me: Q-1 Q-2 Q-3 Q-4 712 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =i-Pr0; R 5 =-i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 713 A=-CH 2

R

2

+R

3

=-(CH

2 3

R

4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 714 A=-CH 2

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 715 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 716 A=-CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Meo; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 717 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4

R

5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 718 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4

R

5

R

6 =Et; Q-1 Q-2 Q-3 Q-4 719 A=CH 2

CH

2

R

2

+R

3

=-(CH

2 3

R

4 =Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 720 A=(CH 2 3

R

2

+R

3 =-t'CH 2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 721 A--CH 2 CHCH; R 2

+R

3

=-(CH

2 3

R

4 -Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 722 A--CH 2 CC; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 723 A--CH 2

CH

2 CHCH; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 *Q-4 724 A--CH 2

CH

2 CC; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 725 A=a-Ph; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 726 A=m-Ph; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5

R

6 Q-1 Q-2 Q-3 Q-4 727 A=p-Ph; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 728 A=(CH 2 3

R

2

+R

3 =-(C11 2 3

R

4 =Et; R 5 =Et; R 6 Et; Q-1 Q-2 Q-3 Q-4 729 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =iPr; R 5 =iPr; R 6 =iPr; Q-1 Q-2 Q-3 Q-4 730 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =ph; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 731 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =tBu; R 5 -Me; R 6 Q-1 Q-2 Q-3 Q-4 732 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =EtQ;, R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 733 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 734 A=(CH 2 3

R

2

+R

3

=-(CH

2

R

4 =EtQ; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 735 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 736 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =n-PrO; R 5 =n-PrO; R 6 =n-PrO; Q-1 Q-2 Q-3 Q-4 737 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =i-PrO; R 5 =i-PrO; R 6 =i-PrO; Q-1 Q-2 Q-3 Q-4 738 A=(CH 2 4

R

2

+R

3

=-(CH

2 3

R

4 =Et, R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 739 A=(CH 2 4

R

2

+R

3

=-(CH

2 3

R

4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 740 A=(CH 2 4

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 =-MeO; Q-1 Q-2 Q-3 Q-4 741 A=(CH 2 4

R

2

+R

3

=-(CH

2

R

4 =EtO; R 5 =Eto; R 6 =Me; Q-1 Q-2 Q-3 -Q-4 742 A=(CH 2 3

R

2 =Me; R 3 =Me; R 4

R

5

R

6 =Et; Q-1 Q-2 Q-3 Q-4 743 A=(CH 2 3

R

2 =Me; R 3 =Me; R 4 =Ph; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 744 A=(CH, 2 3

R

2 =Me; R 3 =Me; R 4 =tBu; R 5 -Me, R 6 =Me; Q-1 Q-2 Q-3 Q-4 745 A=(CH 2 3

R

2 -Me; R 3

R

4 -EtO; R 5 =EtO; R 6 =EtO, Q-1 Q-2 Q-3 Q-4 746 A=(CH 2 3

R

2 -Me; R 3 -Me; R 4 =MaO; R 5 =MeO;, R 6 =MeO; Q-1 Q-2 Q-3 Q-4 747 A=(CH 2 3

R

2 =Et; R 3 =Me; R 4 -Et- R 5 =Et; R 6 =Et; Q-1 Q-2 -Q-3 Q-4 748 A=(Ci1 2 3

R

2 =Et; R 3 =Me; R 4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 WO 95/21846 pCTUS95S/01616 44 749 A=(CH 2 3

R

2 =Et; R 3 =Me; R 4 =tBu; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 750 A=(CH 2 3

R

2 Et; R 3 =Me; R 4 =EtO; R 5 -EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 751 A=(CH 2 3

R

2 -Et; R 3 -Me; R 4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 752 A=(CH 2 4

R

2 =Me; R 3 =Me; R 4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 753 A=(CH 2 4

R

2 =Me; R 3 =Me; R 4 =tBu; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 754 A=(CH 2 4

R

2 =Et; R 3 =Me; R 4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 755 A=(CH 2 4

R

2 -Et; R 3 -Me; R 4 =tBu; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 756 A=(CH 2 4

R

2

+R

3

=CH

2

CH

2

R

4 =Me 3 Si; R 5 =Me 3 Si; R 6 sMe 3 Si; Q-1 Q-2 Q-3 Q-4 757 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =Me 3 Si; R 5 =Me 3 Si; R 6 =Me 3 Si; Q-1 Q-2 Q-3 Q-4 758 A=(CH2)3; R 2

+R

3

CH

2

CH

2

R

4 =Me; R 5

R

6 =Me 3 SiCH 2 Q-1 Q-2 Q-3 Q-4 759 A=(CH 2 3

R

2

+R

3

-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me 3 SiCH 2 O; Q-1 Q-2 Q-3 Q-4 760 A=(CH 2 3

R

2

+R

3

CH

2 CH 1; R 4 =Me; R 5 =Me;

R

6 =-Me 3 SiCH 2 CH2O; 761 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2

CH

2

S;

762 A=(CH 2 3

R

2

+R

3

=CH

2

CH

2

R

4 =Me 3 SiCH 2 O; Q-1 Q-2 Q-3 Q-4

R

5 =Me 3 SiCH 2 O; R 6 =Me 3 SiCH 2

O;

763 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =Me 3 Si(CH 2 2 0; Q-1 Q-2 Q-3 Q-4

R

5 =Me 3 Si(CH 2 2 0; R6=-Me 3 Si(CH 2 2 0; 764 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =MeS; R5=MeS; R 6 -McS; Q-1 Q-2 Q-3 Q-4 765 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =Ph; R 5 =Ph; R 6 Q-1 Q-2 Q-3 -Q4 766 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =nBu; R 5 =nBu; R 6 =nBu; Q-1 Q-2 Q-3 Q-4 767 A=(CH 2 3

R

2

+R

3

-CH

2

CH

2

R

4 =Me; R 5 =Me 3 SiCH 2 Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2 768 A-CH 2

R

2

R

3 =Me; R 4 Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 769 A=-CH 2

R

2 =Me; R 3 =Me; R 4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 770 A=-CH 2

R

2 -Et; R 3 -Et; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 'Q-4 771 A--CH 2 R24R 3

=-CH

2

CH

2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 772 A=-CH 2

R

2

+R

3 -CH(Me)CH2-;,

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 PCT[US95/01616 WO 95/21846 Table 16 ~I COLUMN Q1 Q2 Q3 Q4 773 774 775 776 777 778 779 512 513 514 515 516 517 518 519 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 A=direct bond; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 Me; A=direct bond; R 2

R

3 =Me; R 4 =t-Bu; R 5 =Me; R 6 =Me; A-direct bond; R 2

R

3 =Me; R 4 =Ph; R 5 =Me; R 6 =Me; A=direct bond; R 2

R

3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; A=direct bond; R 2

R

3 =Me; R 4 =t-Bu; R 5 =Ph; R 6 =Ph; A-direct bond, R 2

R

3 =Me; R 4

R

5 =Ph; R 6 =Ph;

A=-CH

2

R

2

R

3 -Me; R 4

R

5 =Me; R 6 =Me;

A=-CH

2

R

2

R

3 -Me; R 4 =Ph; R 5 =Me; R 6 =Me;

A-CH

2

R

2

R

3 =Me; R 4 =i-Pr; R 5 =i-Pr; RO 6 =i-Pr;

A=-CH

2

R

2

R

3 =Me; R 4

R

5 =Ph; R 6 =Ph;

A--CH

2

R

2

R

3 -Me; R 4 =Ph; R 5 =Ph; R 6 =Ph;

A=-CH

2

R

2

R

3 =Me; R 4 =Et; R 5 =Me; R 6 =-Me;

A=-CH

2

R

2

R

3 Me; R 4

CH

2 CH; R 5 =Me; R 6 =Me;, r%=CH 2

R

2

R

3 =Me; R 4

=-CH

2

CHCH

2

R

5 =Me; R 6 =Me;,

A--CH

2

R

2

R

3 =Me; R 4 =EtQ; R 5 =Me; R 6 =Me;

A=-CH

2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =Me; R 6 =Me,

A=-CH

2

R

2

R

3 =Me; R 4 -EtO; r 5 EtO., R 6 -Me-,

A--CH

2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =i-pro; R 6 =Me;

A=-CH

2

R

2

R

3 =Me; R 4 =EtO; R 5 =EtO; R 6 =Eto;

A=-CH

2

R

2

R

3 -Me; R 4 =i-pro; R 5 =i-PrO; R 6 =i-pro;

A-CH

2

R

2

R

3 =Me; R 4

R

5 =Me; R 6 =Me;

A--CH

2

R

2

R

3 =Me; R 4

R

5 =Et; R 6 =Et;

A=-CH

2

CH

2

R

2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me;

A=(CH

2 3

R

2

R

3 =Me; R 4 =Me; R 5

R

6 -Me;

A--CH

2 CHCH;, R 2

R

3 -Me; R 4 -Me; R 5 =Me; R 6 =Me;

A=-CH

2 CC; R 2

R

3 -Me; R 4 -Me; R 5 =Me; R 6 =Me;

A--CH

2

CH

2 CHCH; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R' 6 =Me;,

A=-CH

2

CH

2 CC; R 2

R

3 -Me; R 4 -Me; R 5 =Me; RO=Me; A=o-Ph; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; A=m-Ph; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; A-Ph; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q- 1 Q. 1 Q-1 Q-1 Q-1 Q-1 Q..1 Q-1 Q-1I Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-1 Q-2 Q-3 Q-2 Q-3 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-2 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-3 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 Q-4 WO 95/21846 PCTIUS95/01616 46 796 A=direct bond; R2=Me; R 3 -Me; R 4 -Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 797 A=direct bond; R 2 =Me; R 3

R

4 =t-Bu; R 5 =Me; R 6 Q- 1 Q-2 Q-3 Q-4 798 A=direct bond; R 2 =Me; R 3 -Me; R 4 -Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 799 A=direct bond; R 2 =Me; R 3 -Me; R$-i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 800 A=direct bond; R 2 =Me; R 3

R

4

R

5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 801 A=direct bond; R 2 =Me; R 3 -Me; R 4 -Ph; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 802 A=direct bond; R 2

R

3 =Me; R 4 =Me; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 803 A--CH 2

R

2

R

3 =Me; R 4 =Me; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 804 A=-CH 2

R

2 =Me; R 3 =Me; R 4 =Me; R 5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 805 A-CH 2

R

2 -Me; R 3 =Me; R 4 =t-Bu; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 806 A--CH 2

R

2 =Me; RL-Me; R 4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 807 A=-CH 2

R

2 =Me; R 3 =Me; R4$-i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 808 A--CH 2

R

2 =Me; R 3 =Me; R 4

R

5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 809 A--CH 2

R

2 =Me; R 3 =Me; R 4 =Ph; R 5 -Ph; R 6 -Ph; Q- 1 Q-2 Q-3 Q-4 810 A=-CH 2

R

2

R

3 =Me; R 4 -Et; R 5 -Me; R 6 =Me; Q-1 Q-2 Q -3 Q-4 811 A=-CH 2

R

2 =Me; R 3 =Me; R 4

=-CH

2 CH; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 812 A=-CH 2

R

2 =Me; R 3 =Me; R 4

=CH

2

CHCH-

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 813 A=CH 2

R

2 =Me; R 3 =Me; R 4 =EtO; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 814 A--CH 2

R

2

R

3 =Me; R 4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 815 A--CH 2

R

2 =Mle; R 3 =Me; R 4 =EtO; R 5 =EtO; R 6 Me; Q-1 Q-2 Q-3 Q-4 816 A=-CH 2

R

2 =Me; R 3 =Me; R 4 =i-PrO; R 5 =i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 817 A--CH 2

R

2 =Me; R 3 =Me; R 4 =EtO; R 5 =EtO; R 6 EtO; Q-1 Q-2 Q-3 Q-4 818 A--CH 2

R

2 =Me; R 3 =Me; R 4 =MeO; R 5 =MeO; R 6 =Meo; Q-1 Q-2 Q-3 Q-4 819 A--CH 2

R

2 =Me; R 3 =Me; R 4 =MeO; R 5 =MeQ; R 6 =Me; Q-1 Q-2 Q-3 Q-4 820 A-CH 2 R2=Me; R 3 =Me; R 4 =MeO; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 821 A=-CH 2

R

2 =Me; R 3 =Me; R 4

R

5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 822 A--CH 2

R

2

R

3 =Me; R 4

R

5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 823 A=-CH 2

CH

2

R

2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 824 A--(CH 2 3

R

2 -Me; R 3 -Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 825 A=-CH 2 CHCH; R 2 =Me; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 826 A=-CH 2 CC; R 2 =Me; R 3 =Me; R 4 =Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 827 A--CH 2

CI-

2 CHCH; R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 828 A=-CH 2

CH

2 CC; R 2 =Me; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 829 A=o-Ph; R 2 =Me; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me* Q-1 Q-2 Q-3 Q-4 830 A=m-Ph; RZ=Me; R 3 -Me; R 4 =Me; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-.3 Q-4 831 A=p-Ph; R 2 =Me; R 3 =Me; R 4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 832 A=-CH 2

R

2

R

3 =Me; R 4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q73 Q-4 833 A--CH 2

R

2

R

3 -Me; R 4 =MeO; R 5 =MeO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 834 A=-CH 2

R

2

R

3 =Me; R 4 =MeQ; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 835 A=direct bond; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 836 A=direct bond; R 2 =Et; R 3 =Me; R 4 =t-Bu; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 WO 95/21846 PCT/1S95/01616 47 837 Adirect bond; R 2

R

3 =Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 838 A=direct bond; R 2 =Et; R 3 =Me; R 4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 839 A=direct bond; R 2 =Et; R 3 =Me; R 4 =t-Bu; R 5 =Ph; R 6 =ph; Q-1 Q-2 Q-3 Q-4 840 A=direct bond;, R 2 =Et; R 3 =Me; R 4 =Ph; R 5

R

6 Q-1 Q-2 Q-3 Q-4 841 A=direct bond; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 842 A-CH 2

R

2 -Et; R 3 =Me; R 4 =Me; R 5 -Phv R 6 -Ph; Q-1 Q-2 Q-3 Q-4 843 A--CH 2

R

2 =Et; R 3 =Me; R 4 =t-Bu; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 844 A=CH 2

R

2 =Et; R 3 =Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 845 A--CH 2

R

2 =Et; R 3 =Me; R 4 -i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 846 A=-CH 2

R

2 =Et; R 3 =Me; R 4 -t-Bu- R 5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 847 A--CH 2

R

2

R

3 =Me; R 4 =Ph; R 5 =Ph; R 6 Ph; Q-1 Q-2 Q-3 Q-4 848 A--CH 2

R

2

R

3 -Me* R 4 -Et; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 849 A--CH 2

R

2 -Et; R 3 -Me; R 4

=-CH

2 CH; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 850 A--CH 2

R

2 -Et; R 3 -Me; R 4

-CH

2

CHCH

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 851 A--CH 2

R

2 =Et; R 3

R

4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 852 A--CH 2

R

2 =Et; R 3 =Me; R 4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 853 A--CH 2

R

2 =Et; R 3 =Me; R 4 =EtQ; R 5 =EtQ; R 6 Q-1 Q-2 Q-3 Q-4 854 A=-CH 2 R9-Et; R 3 =Me; R 4 =i-PrO; R 5 =i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 855 A=CH 2

R

2 -Et; R 3 -Me; R 4 =EtO; R 5 -EtO; R 6 -EtO, Q-1 Q-2 Q-3 Q -4 856 A--CH 2

R

2 =Et; R 3 -Me; R 4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 857 A--CH 2

R

2 -Et; R 3 -Me; R 4 =MeQ; R 5 =MeO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 858 A=-CH 2

R

2 -Et; R 3 -Me; R 4 =MeO; R 5 =Me, R 6 =Me; Q-1 Q-2 Q-3 Q-4 859 A=-CH 2

R

2 =Et; R 3 =Me; R 4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 860 A=CH 2

R

2 =Et; R 3 =Me; R 4

R

5 -Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 861 A=-CH 2

CH

2

R

2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 862 A=(CH 2 3

R

2 -Et; R 3 -Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 863 A=CH 2 CHCH; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 864 A=-CH 2 CC;, R 2 =Et; R 3 =Me; R 4 =Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 865 A--CH 2

CH

2 CHCH; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q.-2 Q-3 Q-4 866 A--CH 2 )CH-CC; R 2 =Et; R 3 =Me; R 4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 867 A=o-Ph, R 2

R

3 =Me; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-3 Q-4 868 A=m-Ph; R 2 =Et; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 869 A=p-Ph, R=Et,, R 3 Me 4 M~ 5 me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 870~~ AdR2c bond

R

2

+R

3 -CHCH R=e 5 M;R=e .4 Q.

871 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4 -t-Bu R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 872 A~direct bond; R 2

+R

3

=-CH

2

CH

2

R

4 =Ph;u R 5 =Me; R 6 =Me, Q-1 Q-2 Q-3 'Q-4 873 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4 =iP; R 5

R

6 Q-1 Q-2 Q-3 Q-.4 874 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4

R

5

R

6 =iP; Q I Q-2 Q-3 Q-4 875 A=direct bond; R 2

+R

3

=~-CH

2

CH

2

R

4 =PhB; R 5 =Ph; R 6 =Ph; Q,1 Q-2 Q-3 Q-4 876 A=direct bond; R 2

+R

3

=-CH

2

CH

2

R

4

R

5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 877 A=drcH 2 n; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =ph; R 6 =Ph Q-1 Q-2 Q-3 Q.-4 WO 95/21846 PCT[JS9S101616 48 878 A=-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =t-B3u; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 879 A-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Ph; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 880 A=CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 881 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =t-Bu; R 5 -Ph; R 6 -Ph; Q-1 Q-2 Q-3 Q-4 882 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 883 A=CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Et; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 884 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

-CH

2 CH; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 885 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

-CH

2

CHCH

2

R

5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 886 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 887 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 888 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 -EtQ; R 6 =Me; Q-1 Q-2 Q-3 Q-4 889 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =i-PrO; R 5 =i-pro; R 6 =Me; Q-1 Q-2 Q-3 Q-4 890 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 891 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =MeO; R 5 =MeO; R 6 MeO; Q-1 Q-2 Q-3 Q-4 892 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =MeQ; R 5 =MeO;, R 6 =Me; Q-1 Q-2 Q-3 Q-4 893 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 -MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 894 A=CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 895 A--CH 2

R

2

+R

3

=-CH

2

CH

2

R

4

R

5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 896 A--CH 2

CH

2

R

2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 897 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 898 A--CH 2 CHCH; R 2

+R

3

=-CH

2

CH

2

R

4 -Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 899 A--CH 2 CC; R 2

+R

3

=-CH

2 CH2-; R 4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 900 A--CH 2

CH

2 CHCH; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 901 A--CH 2

CH

2 CC; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 902 A~o-Ph; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 903 A=m-Ph; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 904 A=p-Ph; R 2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 905 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 -Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 906 A=direct bond; R 2

+R

3 =-CH(Me)CH2-;

R

4

R

5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 907 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4

R

5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 908 A~direct bond; R 2

+R

3 =-CH(Me)CH2-,

R

4 =i-Pr; R 5 =i-Pr; Q-1 Q-2 Q-3 Q-4

R

6 -i-Pr; 909 A=direct bond; R 2

+R

3 -CH(Me)CH2-

R

4 =t-Bu; R 5 =Ph; Q-1 Q-2 Q-3 Q-4

R

6 =Ph; 910 A=direct bond; R 2

+R

3 CH(Me)CH2-;

R

4 =Ph; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 WO 95/21846 pCTfi'S95101 616 911 A=direct bond; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Ph; Q-1 Q-2 Q-3 Q-4

R

6 =Ph; 912 A--CH 2

R

2

+R

3 =-CH(Me)CH2-;

R

4 -Me; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 913 A=CH- 2

R

2

+R

3 =-CH(M~e)CH 2

R

4

R

5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 914 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 915 A-CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-Pr; R 5 =i-Pr; R 6 =i-Pr; Q-1 Q-2 Q-3 Q-4 916 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =t-Bu; R 5 =Ph; R 6 Q-1 Q-2 Q-3 Q-4 917 A-CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 918 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -Et; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 919 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

-CH

2 CH; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 920 A-CH 2

R

2

+R

3 CH(Me)CH 2

R

4

CH

2

CHCH

2

R

5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =me; 921 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -EtQ; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 922 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-PrO; R 5 =Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 923 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 -EtQ; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 924 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =i-PrO; R 5 =i-PrO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 925 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO; R 5 =Eto; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 926 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =MeO; Q-1 Q-2 Q-3 Q-4

R

6 =MeO; 927 A--CH 2 RZ2+p 3 .(Me)CH 2

R

4 =MeO; R 5 =MeQ; R 6 =Me; Q-1 Q-2 Q-3 Q-4 928 A=CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 929 A--CH 2

R

2

+R

3 =-CH(Me)CH2-,

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 930 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

R

5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 931 A--CH 2

CH

2

R

2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 932 A=(CH 2 3

R

2

+R

3 CH(Me)CH 2

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 933 A--CH 2 CHCH; R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 934 A--CH 2 CC; R 2

+R

3 =-CH(Me)CH2-;

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 935 A--CH 2

CH

2 CHCH; R 2

+R

3 =-CH(Me)CH 2

R

4 -Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 936 A--CH 2

CH

2 CC, R 2

+R

3 =-CH(Me)CH 2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me; 937 A=o-Ph; R 2

+R

3 =-CH(Me)CH2-;

R

4 =Me; R 5 =me; R 6 -me; Q-1 Q-2 Q-3 Q-4 938 A=m-Ph;, R 2

,+R

3 =-CH(Me)CH 2

R

4 -Me; R 5 -Me; R 6 =me; Q-1 Q-2 Q-3 Q-4 939 A=p-Ph; R 2

+R

3 =-CH(Me)CH2-;

R

4 -Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 940 A=(CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 941 A=(CH 2 3

R

2

+R

3

=-CH

2

)CH

2

R

4 =iPr; R 5 =iPr; R 6 =iPr; Q-1 Q-2 Q-3 Q-4 942 A=(CH 2 3

R

2 3

=-CH

2

CH

2 R=Ph; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 943 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 -tBu; R 5 -Me; R 6 Q-1 Q-2 Q-3 Q-4 944 A=(CH 2 3

R

2

+R

3

-CH

2

CH

2

R

4 =EtO; R 5 -Eto; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 945 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 WO095/21846 1'CT[US9S/01616 946 A=(CH 2 3

R

2

+R

3

=-CH

2 C11 2

R

4 =EtO; R 5 =Eto; R 6 =Me; Q-1 Q-2 Q-3 Q-4 947 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 -EtO; R 5

R

6 =Me; Q-1 Q.-2 Q-3 Q-4 948 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 -n-PrO; R 5 =n-PrO; R 6 Q-1 Q-2 Q-3 Q-4 PrO; 949 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =i-PrO; R 5 =i-PrO; R 6 Q-1 Q-2 Q-3 Q-4 Pro; 950 A=(CH 2 3

R

2 -iR 3 =-CH(Me)CH 2

R

4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 951 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =iPr; R 5 =iPr; R 6 =iPr; Q-1 Q-9- Q-3 Q-4 952 A=(CH 2 3

R

2

+R

3 CH(Me)CH 2

R

4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 953 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =tBu; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 954 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtO; R 5 =EtO; Q-1 Q-2 Q-3 Q-4

R

6 =EtO; 955 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =MeO; Q-1 Q-2 Q-3 Q-4 956 =CH 2 +R-C(eC -REt;R=t;R-e Q- Q2 Q3 Q4 957 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =Eto; R 5 =MEt; R 6 =Me, Q-1 Q-2 Q-3 Q-4 958 A=(CH 2 3

R

2

+R

3 =-CH(Me)CH 2

R

4 =EtPO; R 5 Q-1 Q-2 Q-3 Q-4 959 A=(CH 2 3

R

2

+R

3 CH(Me)CH 2

R

4 =i-PrO; R 5 z=i-PrO; Q-1 Q-2 Q-3 Q-4

R

6 =n-PrO; 960 A=(CH 2

R

2

+R

3

CH

2

MCH

2

R

4 r 5 O; R 6 ,=Etpr; Q-1 Q-2 Q-3 Q-4 961 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 -Et; R 5 Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 962 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =MEO; R 5 =MEO; R 6 =MEO; Q-1 Q-2 Q-3 Q-4 963 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =MEto; R 5 =eto; R 6 =Me; Q-1 Q-2 Q-3 Q-4 964 A=(CH 2 4

R

2

+R

3

=-CH(MCH

2

R

4 Et; R 5 Et; R 6 =Me; Q-1 Q-2 Q-3 Q-4 965 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH2-;

R

4 =Et; R 5 =EtO 6; Q.-1 Q-2 Q-3 Q-4

R

6 =EtO; 966 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH 2

R

4 =MeO; R 5 =Meo; Q-1 Q-2 Q-3 Q-4

R

6 =MeO; 967 A=(CH 2 4

R

2

+R

3 =-CH(Me)CH2-;

R

4 -EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 968 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Ph; R 6 Ph; Q-1 Q-2 Q-3 Q-4 969 A--CH 2

R

2

+R

3

=-(CH

2

R

4

R

5 =Me; R 6 =Me; Q- 1 Q-2 Q-3 Q-4 970 A--CH 2

R

2

+R

3

=-(CH

2

R

4 =Ph; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 971 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =i-Pr; R 5

R

6 =i-Pr; Q-1 Q-2 Q-3 Q-4 972 A--GH 2

R

2

+R

3

=-(CH

2

R

4 =t-Bu; R 5 -Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 973 A--CH 2

R

2

+R

3

=-(CH

2

R

4 =Ph; R 5 =Ph; R 6 =Ph; Q-1 Q-2 Q-3 Q-4 974 A--CH 2

R

2

+R

3

=-(CH

2

R

4 =Et; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 975 A=-CH 2

R

2

+R

3

=-(CH

2 3

R

4

CH

2 CH; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 976 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4

CH

2

CHCH

2

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 977 A=-CH 2

R

2

.+R

3

=-(CH

2 3

R

4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 WO095/21846 PCk, dS9S/01616 51 978 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =i-PrO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 I 979 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 980 A=CH 2

R

2

+R

3

=-CCH

2 3

R

4 =i-PrO; R 5 =i-pro; R 6 =Me; Q-1I Q-2 Q-3 Q-4 981 A-CH 2

R

2

+R

3

=-(CH

2 3

R

4 =EtQ;, R 5 =EtO; R 6 =EtO; Q-1I Q-2 Q-3 Q-4 982 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =MeQ; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 983 A--CH 2

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeQ; R 6 =Me; Q-1 Q 2 Q-3 Q-4 984 A--GH 2

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 985 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4

R

5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 986 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4

R

5 -Et, R 6 -Et: Q-1 Q-2 Q-3 Q-4 987 A=CH 2

R

2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 988 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 989 A--CH 2 CHCH R 2

+R

3

=-(CH

2 3

R

4 -Me; R 5 -Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 990 A=CH 2 CC; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 991 A--CH 2

CH

2 CHCH; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4 Q-.i

R

6 =Me; 992 A--CH 2

CH

2 CC-, R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 993 A=o-Ph; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 994 A=m-Ph; R 2

+R

3

=-(CH

2 3

R

4 =Me; R 5 =Me; RO--Me; Q-1 Q-2 Q-3 Q-4 995 A=p-Ph; R 2

+R,

3

=-(CH

2 3

R

4 =Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 9s A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =Et; R 5 =Et; R 6 Et; Q-1 Q-2 Q-3 Q-4 9s A=(CH 2 3

R

2

+R

3 =-tCH 2 3

R

4 =iPr; R 5 =iPr; R 6 =iPr; Q-1 IQ-2 Q-3 Q-4 998 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 999 A=(CH2) 3

R

2

+R

3

=-(CH

2 3

R

4 =tBu; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 1000 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =EtQ; R 5 -EtO, R 6 =EtO; Q-1 Q-2 Q-3 Q-4 1001 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 1002 A=(CH 2 3

R

2

+R

3 =-(CH29 3

R

4 =Eto; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-.3 -Q-4 1003 A=(CH 2 3

R

2

+R

3

(CH

2 3

R

4 =EtO; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1004 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =n-PrO;, R 5 =n-PrO; Q-1 Q-2 Q-3 i Q-4

R

6 =n-PrO; 1 1005 A=(CH 2 3

R

2

+R

3

=-(CH

2 3

R

4 =i-PrO; R 5 -i-PrO; Q-1 Q-2 Q-3 Q-4

R

6 =i-prO; 1006 A=(CH 2 4

R

2

+R

3

R

4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-.4 1007 A=(CH 2 4

R

2

+R

3

R

4 =Eto; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 1008 A=(CH 2 4

R

2

+R

3

=-(CH

2 3

R

4 =MeO; R 5 =MeO; R 6 -MeO;, Q-1 Q-2 Q-3 Q-4 1009 A=(CH 2 4

R

2

+R

3

=-(CH

2 3

R

4 =EtO; R 5 =EtO; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1010 A=(CH 2 3

R

2

R

3 =Me; R 4 =Et; R 5 =Et; R 6 =Et; Q-1 Q-2 Q-3 Q-4 1011 A=(CH 2 3

R

2 =Me; R 3 -Me; R 4 -Ph; R 5 =Me; R 6 =Mc; Q-1 Q-2 Q-3 Q-4 1012 A=(CH 2 3

R

2 =Me; R 3 =Me; R 4 =tBu; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 WO 95/21846 PCTIUS9S/01616 52 1013 A=(CH 2 3

R

2 =Me; R 3

R

4 =EtO; R 5 =EtQ; R 6 Q-1 Q-2 Q-3 Q-4 1014 A=(CH 2 3

R

2 =Me; R 3 =Me; R 4 =MeQ; R 5 =MeO; R 6 =MeO; Q-1 Q-2 Q-3 Q-4 1015 A=(CH 2 3

R

2 -Et; R 3 -Me; R 4 =Et; R 5 =Et, R 6 Q-1 Q-2 Q-3 Q-4 1016 A=(CH 2 3

R

2

R

3 =Me- R 4 -Ph; R 5

R

6 =Me; Q-1 Q-2 Q-3 Q-4 1017 A=(CH 2 3

R

2

R

3 -Me; R 4 =tBu; R 5 -Me; R 6 -Me; Q-1 Q-2 Q-3 Q-4 1018 A=(CH 2 3

R

2 =Et; R 3 =Me; R 4 =EtO; R 5 =EtO; R 6 =EtO; Q-1 Q-2 Q-3 Q-4 1019 A=(CH 2 3

R

2 =Et; R 3 =Me; R 4 MeO; R 5 =MeO; R 6 =-MeO; Q-1 Q-2 Q-3 Q-4 1020 A=(CH 2 4

R

2 Me; R 3

R

4 =Ph; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1021 A=(CH 2 4

R

2 =Me; R 3 =Me; R 4 =tBu; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 1022 A-(CH 2 4

R

2 =Et; R 3 =Me; R 4 =Ph; R 5 =1Ae; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1023 A=(CH 2 4

R

2 =Et; R 3 =Me; R 4 -tBu; R 5

R

6 -Me; Q-1 Q-2 Q-3 Q-4 1024 A=(CH 2 4

R

2

+R

3

=-CH

2

CH

2

R

4 =Me 3 Si:, R 5 =Me 3 Si; Q-1 Q-2 Q-3 Q-4

R

6 =-Me 3 Si; 1025 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 -Me 3 Si; R 5 =Me 3 Si; Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 Si; 1026 A-(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2 1027 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =Me; R 5 =Me; Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2

Q;

1028 A=(CH 2 3

R

2

+R

3

-CH

2

CFI

2

R

4

R

5 Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2

CH

2

O;

1029 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 -Me; R 5 =Me; Q-1I Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2

CH

2

S'

1030 A=(CH 2 3

R

2

+R

3

=-CH

2

CH

2

R

4 =Me 3 SiCH 2 O; Q-1 Q-2 Q-3 Q-4

R

5 =Me 3 SiCH 2 O; R 6 =-Me 3 SiCH 2

Q;

1031 A=(CH 2 3

R

2

+R

3

=CH

2

CH

2

R

4 =Me 3 Si(CH 2 2 0; Q-1 Q-2 Q-3 Q.-4

R

5 =Me 3 Si(CH 2 2 0- R6=-Me 3 Si(CH 2 2 0; 103? A=(CH 2 3

R

2

+R

3

-CH

2

CH

2

R

4 =MeS-, R 5 =MeS; R 6 =MeS; Q-1 Q-2 Q-3 Q-4 1033 A=(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4

R

5 =Ph; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1034 A=-(CH 2 3

R

2

+R

3

CH

2

CH

2

R

4 =nBu;, R 5 =nBu; R 6 =nBu;, Q-1 Q-2 Q-3 Q-4 1035 A--(CH 2 3

R

2

+R

3

-CH

2

CH

2

R

4 =Me; R 5 =Me 3 SiCH 2 Q-1 Q-2 Q-3 Q-4

R

6 =Me 3 SiCH 2 1036 A--CH 2 R7=H; R 3 =Me; R 4 =Me; R 5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 1037 A=-CH 2

R

2 =Me; R 3 =Me; R 4 -Me; R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1038 A--CH 2

R

2 =Et; R 3

R

4 -Me* R 5 =Me; R 6 =Me; Q-1 Q-2 Q-3 Q-4 1039 A=-CH 2

R

2

+R

3

=-CH

2

CH

2

R

4 =Me; R 5 =Me, R 6 =Me, Q-1 Q-2 Q-3 Q-4 1040 A--CH 2

R

2

+R

3 =-CH(Me)CH 2

R

4

R

5 =Me; R 6 Q-1 Q-2 Q-3 Q-4 ii F;1 1 WO 95/21846 PCIT/US95/0116 53 Formulation/Utility Compounds of this invention will generally be used in formulation with an agriculturally suitable carrier comprising a liquid or solid diluent. Useful formulations include dusts, granules, baits, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like, consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up 100 weight percent.

Weight Percent Ingrdiient Diluent Surfactant Wettable Powders 5-90 0-74 1-10 Oil Suspensions, Emulsions, 5-50 40-95 0-15 Solutions, (including Emulsifiable Concentrates) Dusts 1-25 70-99 Granules, Baits and Pellets 0.01-99 5-99,99 0-15 High Strength Compositions 90-99 0-10 0-2 Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents and solvents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, and the like.

Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer mill or fluid energy mill.

Water-dispersible granules can be produced by agglomerating a fine powder composition; see for example, Cross et al., Pesticide Formulations, Washington, D.C., 1988, pp 251-259. Suspensions are prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, I IC -Is WO 95/21846 PCT/US95/01616 54 "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-148, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546.

For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. ine 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138 -140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A.

Example A Wettable Powder Compound 1 65.0% dodecylphenol polyethylene glycol ether sodium ligninsulfonate sodium silicoaluminate montmorillonite (calcined) 23.0%.

Example B Granule Compound 1 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; U.S.S. No.

25-50 sieves) 90.0%.

Example C Extruded Pellet Compound 1 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate sodium alkylnaphthalenesulfonate calcium/magnesium bentonite 59.0%.

Example D Emulsifiable Concentrate Compound 1 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.

I ii Il P- WO 95/21846 PCTUS95/01616 The compounds of this invention exhibit activity against a wide spectrum of foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests. Nevertheless, all of the compounds of this invention display activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs, foliar-feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs, larvae, nymphs and adults of the Order Acari; eggs, immatures and adults of the Orders Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera; and eggs, junveniles and adults of the Phylum Nematoda. The compounds of this invention are also active against pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria, Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum Platyhelminthes..

Specifically, the compounds are active against southern corn rootworm (Diabrotica undecimpunctata howardi), aster leafhopper (Mascrostelesfascifrons), boll weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm (Spodopterafrugiperda), black bean aphid (Aphisfabae), green peach aphid (Myzus persica), cotton aphid (Aphis gossypii), Russian wheat aphid (Diuraphis noxia), English grain aphid (Sitobion avenae), tobacco budworm (Heliothis virescens), rice water weevil (Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper (Sogatellafurcifera), green leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug (Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocorisa chinensis), slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The compounds are active on mites, demonstrating ovicidal, larvicidal and chemosterilant activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani, Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis, Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis, Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus lewisi, Brevipalpus phoenicis, Brevipalpus californicus and Brevipalpus obovatus; Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus, Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more detailed pest descriptions.

II

WO 95/21846 PCTIUS95/01616 56 Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellants, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of other agricultural protectants with which compounds of this invention can be formulated are: insecticides such as avermectin B, monocrotophos, carbofuran, tetrachlorvinphos, malathion, parathion-methyl, methomyl, chlordimeform, diazinon, deltamethrin, oxamyl, fenvalerate, esfenvalerate, permethrin, profenofos, sulprofos, triflumuron, diflubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphosmethyl, chlorpyrifos, dimethoate, fipronil, flufenprox, fonophos, isofenphos, methidathion, minetha-midophos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, tefluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, imidacloprid, metaldehyde and rotenone; fungicides such as carbendazim, thiuram, dodine, maneb, chloroneb, benomyl, cymoxanil, fenpropidine, fenpropimorph, triadimefon, captan, thiophanate-methyl, thiabendazole, phosethyl-Al, chlorothalonil, dichloran, metalaxyl, captafol, iprodione, oxadixyl, vinclozolin, kasugamycin, myclobutanil, tebuconazole, difenoconazole, diniconazole, fluquinconazole, ipconazole, metconazole, penconazole, propiconazole, uniconzole, flutriafol, prochloraz, pyrifenox, fenarimol, triadimenol, diclobutrazol, copper oxychloride, furalaxyl, folpet, flusilazol, blasticidin S, diclomezine, edifenphos, isoprothiolane, iprobenfos, mepronil, neo-asozin, pencycuron, probenazole, pyroquilon, tricyclazole, validamycin, and flutolanil; nematocides such as aldoxycarb, fenamiphos and fosthietan; bactericides such as oxytetracyline, streptomycin and tribasic copper sulfate; acaricides such as binapacryl, oxythioquinox, chlorobenzilate, dicofol, dienochlor, cyhexatin, hexythiazox, amitraz, propargite, tebufenpyrad and fenbutatin oxide; and biological agents such as entomopathogenic bacteria, virus and fungi.

In certain instances, combinations with other arthropodicides having a similiar spectrum of control but a different mode of action will be particularly advantageous for resistance management.

Arthropod pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or more of the compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus, the present invention further comprises a method for the control of foliar and soil inhabiting arthropods and nematode pests and protection of agronomic and/or nonagronomic crops, comprising applying one or more of the compounds of Formula I, or compositions containing at least one such compound, in an effective amount, to the environment of the pests IL ll I I WO 95/21846 PCTIUS95101616 57 including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. A preferred method of application is by spraying. Alternatively, granular formulations of these compounds can be applied to the plant foliage or the soil. Other methods of application include direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The compounds can be incorporated into baits that are consumed by the arthropods or in devices such as traps and the like.

The compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, and synergists and other solvents such as piperonyl butoxide often enhance compound efficacy.

The rate of application required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required.

The following TESTS demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of arthropod development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species, See Index Tables A-E for compound descriptions.

Index Table A R0 2 N SiMe 3 I I

R

2

R

3 ~CT~e -PPT sr~l WO 95121846 WO 9521846PCTIUS95101616 Cmpd R__ 3-CH 2 -6-CI-pyr 3-CH 2 -6-Cl-pyr 3-CH 2 -6-CI-pyr 2 -2-CI-thiazolyl 2 -2-CI-thiazolyl MeSCH 2

CH

2 MeSCHICH 2 3-CH 2 -pyr 3-CH 2 -pyr 3-CH 2 -5,6-iC-pyr 3-CH 2 -6-Cl-pyr 2 -3-Me-isoxazolyl R2+ R 3

-CH(CH

3

)CH

2 (b)

-CH(CH

3

)CH

2 (b)

-CH

2

CH-

2

-CH

2

CH

2

-CH(CH

3

)CH

2

-CH

2

CH

2

CH(CH

3

)CH

2 (b)

-CH

2

CH

2

-CH(CH

3

)CH

2

-CH

2

CH

2

-CH

2

CH

2 M.P. (TC) 112-115 145- 147 145.5-147.0 148-151 133-137 105-107 oil 158.5-160.0 155.0-156.5 162.5-164.0 89-93 116-118 config (a) racemic

R

achiral achiral racemic achiral racemic achiral racemic achiral achiral achiral Cnipd 13 3-CH 2 -6-CI-pyr

M.P.(OC

oil config (a) achiral Configuration refers to the configuration at the chiral carbon. The "R" designation is defined according to the Cahn, Ingold and Prelog procedure.

"Racemic" is defined as a substantially equal mixture of both R and S enantiomers.

"Achiral" denotes compounds which do not contain a chiral center.

CH carbon atom is attached to the nitrogen atom which contains R 1 Index Table B cmad 14 16 17 18 19

A

(CH

2 3

(CH

2 3

(CH

2 3

(CH

2 4

(CH

2 3

BR

4 EtO MeO EtO EtO EtO Ph EtO MeO EtO Eta EtO me DtO MeO Me Me EtO Me 140-142 87-90 112-114 97-98 138-140 147-149 config (a) achiral achiral achiral achiral ra~eniC achiral WO 95/21846 WO 9521846PCTIUS95IOI616

CH

2

CH

2

(CH

2 3

(CH

2 3

(CH

2 3

(CH

2 3

(CH

2 3 oil oil 81-85 133-136 152-153 148-150 144-149 racemidc

R

racemic achiral achiral achiral achiral Configuration refers to the configuration at the chiral carbon. The tIR" designation is defined according to the Cahm, Ingold and Prelog procedure. "Raceic" is defined as a substantially equal mixture of both R and S enantiomers. Achiral denotes compounds which do not contain a chiral center.

The following additional notations have been used to represent various embodiments of Q in Table C: Q-1 6-CI-3-pyridyl, Q-2 5,6-dichloro-3-pyridyl, Q-3 2-chloro-5-tii:azolyl and Q-5 CH 3

SCH

2 Index Table C 27 28 29 31 32 33 (a) (b) -Q R Q-3 H Q-1 H Q-5 Me(a) Q-1 H Q-1 Me(b) Q-2 H Q-2 H Racemric R-enantiomer

A

CH

2

(CH

2 3

CH

2

CH

2

CH

2 oil 104-106 oil 152.5-154.0 108-1 134-141 98-104 WO 95/21846 PCT/US95/01616 Index Tabk D 02N R4 Cmpdl- R6A 34 3-CH 2 -6-CI-pyr- CH 2 Si Et Me Me 115-117 3-CH 2 -6-CI-pyr CH 2 Si Ph Me Me oil Index Table E IH NMR (CDCII) DATA (a) Crnpd. No.

7 4.47-4.36 4.02 3.90-3,73 (ni,4H), 3.49 (dt, 1H), 3.22 (dd,1H), 2.82-2.68 2.12 2.08 (ABq,2H), 1.39 0. 10 (OH).

13 8.30 7.69 (dd,1H), 7.32 4.50 4.18 (d,1H), 3.60-3.40 3.32-3.21 2.99 1.97 (s,211), 1.19 t,3H), 0. 10 (s,9H).

(300 MHz) 8.31 7.78 (dd,1H), 7.50 (dd,2H), 7.40-7.32 (m,3H), 7.30 5.08 4.65 3.9-3.65 3.18 (t,1H), 2.83 (dd,1H), 2.19 (ABq,2H), 1.19 0.39 0.35 (s,3H).

21 (300 MHz) 8.32 (d,1IH), 7.79 (dd, 1H), 7.52 (dd,2H), 7.42-7.35 (m,3H), 7.30 5.07 4.66 3.9-3.65 3.17 (t,1H), 2.83 (dd,1H), 2.19 (ABq,2H), 1.19 0.39 0.35 (s,3H).

22 (300 MHz) 8.30 7.80 7.50-7.40 7.40-7.30 7.30 5.00 4.75 3.90-3.65 (m,6H), 3.20-3. 10 (m,1IH), 2.40-2.30 1.60-1.45 1.24 (d,3H), 0.80-0.70 0.28 (s,6H).

26 8.35 7.85 7.60 7.55-7.50 7.43-7.35 4.79 3.84 3.78 3.51 2.5 (t,2H), 1.80-1.65 1.45-1.35 (m,2H).

27 (300 MHz) 7.52 (dd,2H), 7.45 7.42-7.35 4.93 (s,2H), 3.81 3.78 3.54 (distorted t,2H), 3.14 (distorted t,2H), 2.28 0.38 (s,6H).

I

WO 95/21846 PCT/US95/01616 61 29 (300 MHz) 7.57 (dd,2H), 7.39 4.40 3.93-3.82 (m,4H) 3.72 3.45 3.34 2.85 .8-2.6 (m,2H), 2.35 (ABq,2H), 2.10 1.31 0.40 0.36 (s,3H).

32 (300 MHz) 8.26 8.07 4.85 3.91 3.78 3.63 2.07 0.96 0.58 0.09 (s,6H).

33 (300 MHz) 8.27 8.05 7.55 7.40 4.82 3.82 3.79 3.46 3.15 (distorted t,2H), 2.31 0.40 (s,6H).

8.30 7.64 (apparent d,lH), 7.54 7.38 7.31 4.59 (br s,2H), 3.72 3.27 3.11 2.17 1.97 0.39 (s,6H).

Unless indicated otherwise, spectra were obtained in CDC13 at 400MHz.

Chemical shift values are relative to Me 4 Si 0.O0ppm. s singlet, d doublet, t triplet, q quartet, m multiplet.

TEST A Fall Armyworm Test units, each consisting of a H.I.S. (high impact styrene) tray with 16 cells were prepared. Wet filter paper and approximately 8 cm 2 of lima bean leaf was placed into twelve of the cells. A 0.5 cm layer of whett germ diet was placed into the four remaining cells. Fifteen to twenty third-instar larvae of fall armyworm (Spodoptera frugiperda) were placed into a 230 mL (8 ounce) plastic cup. Solutions of each of the test compounds in 75/25 acetone/distilled water solvent were sprayed into the tray and cup. Spraying was accomplished by passing the tray and cup on a conveyer belt directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.55 kg of active ingredient per hectare (about 0.5 pounds per acre) at 207 kPa (30 The insects were transferred from the 230 mL cup to the H.I.S. tray (one insect per cell).

The trays were covered and held at 27 0 C and 50% relative humidity for 48 h, after which time readings were taken on the twelve cells with lima bean leaves. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 1, 2, 3, 6, 14*, 19*, 27*, 28*, 29*, 30*, 31* and 27*.

tested at 0.14 kg/ha.

TEST B Southern Corn Rootworm Test units, each consisting of a 230 mL (8 ounce) plastic cup containing a 2.54 cm 2 plug (1 square inch) of a wheatgerm diet, were prepared. The test units were sprayed as described in TEST A with individual solutions of the test compounds. After the spray on the cups had dried, five second-instar larvae of the southern corn L -II I ~Jr __1 WO 95/21846 PCT/US95/01616 62 rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. The cups were held at 27 0 C and 50% relative humidity for 48 h, after which time mortality readings were taken. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14*, 15*, 16*, 20*, 21*, 22*, 24*, 26*, 27*, 28*, 30*, 32* and 34*.

tested at 0.14 kg/ha.

TEST C Aster Leafhopper Test units were prepared from a series of 350 mL (12 ounce) cups, each containing oat (Avena sativa) seedlings in a 2.54 cm (1 inch) layer of sterilized soil. The test units were sprayed as described in TEST A with individual solutions of the test compounds.

After the oats had dried from the spraying, 10 to 15 adult aster leafhoppers (Mascrostelesfascifrons) were aspirated into each of the cups. The cups were covered with vented lids and held at 27 0 C and 50% relative humidity for 48 h, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 1, 2, 3, 4, 5, 6, 7, 10, 11, 13, 14* and 16*, 19*, 20*, 21*, 23*, 24*, 25*, 26*, 27*, 28*, 29*, 30*, 31*, 32* and 34*.

tested at 0.14 kg/ha.

TEST D Boll Weevil Test units consisting of 260 mL (9 ounce) cups containing five adult boll weevils (Anthonomus grandis grandis) were prepared. The test units were sprayed as described in TEST A with individual solutions of the test compounds. Each cup was covered with a vented lid and held at 27 0 C and 50% relative humidity for 48 h, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 2, 3, 4, 5, 6, 7, 10 and 16*.

tested at 0.14 kg/ha.

TEST E Black Bean Aphid Individual nasturtium leaves were infested with 10 to 15 aphids (all morphs and growth stages of Aphisfabae) and sprayed with their undersides facing up as described in TEST A. The leaves were then set in 0.94 cm (3/8 inch) diameter vials containing 4 mL of sugar solution (approximately 1.4 g per liter) and covered with a clear plastic 29 mL (1 ounce) cup to prevent escape of the aphids that drop from the leaves. The test units were held at 27 0 C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14*, 15* and 16*, 19*, 21*, 22*, 23*, 24*, 25*, 26*, 28*, 29*, 30*, 31*, 32* and 34*.

tested at 0.14 kg/ha.

L ~L -LI ~plp~W WO 95/21846 PCT/US95/01616 63 TEST F Contact Activity Against Green Leafhopper Nymphs Three rice (Oryza sativa) seedlings, 1.5 leaf stage and about 10 cm tall were transplanted into a 14 mL (1/2 ounce) plastic cup containing Kumiai Brown artificial soil. Seven milliliters of distilled water were then added to the cup. The test chemical was prepared by first dissolving the chemical in acetone and then adding water to produce a final test concentration of 75:25 (acetone:water). Four plastic cups, each cup serving as a replicate, were then placed on a spray chamber turntable. The cups were sprayed for 45 seconds with 50 mL of the chemical solution at a pressure of 2.0 kg/cm 2 with air atomizing spray nozzles. The turntable completes 7.5 rotations during the second spray interval. After chemical application, the treated cups were held in a vented enclosure to dry for about 2 h. After drying, the cups were placed into conical shaped test units and the surface of the soil covered with 2 to 3 mm of quartz sand.

Eight to ten 3rd-instar nymphs of the green leafhopper (Nephotettix cincticeps) were transferred into the test units using an aspirator. The test units were held at 27°C and relative humidity. Counts of the number of live and dead nymphs were taken at 24 and 48 h post-infestation. Insects which cannot walk are classified as dead. Of the compounds tested, the following gave mortality levels of 80% or higher at 48 h at an application rate equivalent to 0.05 kilograms per hectare: 1, 2, 3 4, 5, 6, 7 and 8.

TEST G Contact Activity Against Brown Planthopper Nymphs Three rice (Oryza sativa) seedlings, 1.5 leaf stage and about 10 cm tall were transplanted into a 14 mL (1/2 ounce) plastic cup containing Kumiai Brown artificial soil. Seven milliliters of distilled water was then added to the cup. The test chemical was prepared by first dissolving the chemical in acetone and then adding water to produce a final test concentration of 75:25 (acetone:water). Four plastic cups, each cup serving as a replicate, were then placed on a spray chamber turntable. The cups were sprayed for 45 seconds with 50 mL of the chemical solution at a pressure of 2.0 kg/cm 2 with air atomizing spray nozzles. The turntable completes 7.5 rotations during the 45 second spray interval. After chemical application, treated cups were held in a vented enclosure to dry for about 2 h. After drying, the cups were placed into conical shaped test units and the surface of the soil covered with 2 to 3 mm of quartz sand. Eight to ten 3rd-instar nymphs of the brown planthopper (Nilaparvata lugens) were then transferred into the test units using an aspirator. The test units were held at 27 0 C and 65% relative humidity. Counts of the number of live and dead nymphs are taken at 24 and 48 h post-infestation. Insects which cannot walk are classified as dead. Of the compounds tested, the following gave mortality levels of 80% or higher at 48 h at an application rate equivalent to 0.05 kilograms per hectare: 1, 2, 3, 4, 5, 6, 7, 8 and 9.

I 1 1

Claims

1. A compound of the formula 16 R R RL__GjN/A R2 R 3 I wherein X is selected from the group Si and Ge; A is selected from the group C I -C 20 alkylene, C 2 -C 20 alkenylene, C 2 -C 20 alkynylene, C 3 -C 8 cycloalkylene, C 7 -C 10 aralkylene and phenylene, each group optionally substituted with 1-3 substituents independently selected from W; or A is a direct bond; R 1 and R 3 are independently selected from the group H, C I -C 10 alkyl, C 2 -C 10 alkenyl or C 2 -C 1 0 alkynyl, each group optionally substituted with 1-2 substituents independently selected from the group halogen, CN, C(O)R 7 C(S)R 7 NO 2 OH, SC(O)R 7 SC(S)R 7 OC(O)R 7 OC(S)R 7 NR 8 C(O)R 7 NR 8 C(S)R 7 SH, Si(R 8 C 1 -C 4 alkoxy, CI-C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 8 cycloalkyl and phenyl optionally substituted with 1-3 substituents independently selected from W 1 C 3 -C 8 cycloalkyl optionally substituted with 1-3 substituents independently selected from the group halogen, CI-C 2 alkyl and C 1 -C 2 haloalkyl; C(O)R 1 1; C(S)R 1 1; phenyl optionally substituted with 1-3 substituents independently selected from W 1 C 1 -C 3 alkyl substituted with a or 6-membered aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from W 1 and a 5- or 6-membered aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from W 1 R 2 is selected from the group H, CI-C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halocycloalkyl and C4-C 7 cycloalkylalkyl, each group optionally substituted with 1-3 substituents independently selected from W; or II -LIB WO 95/21846 PCT/US95/01616 R 2 and R 3 can be taken together as CH 2 CH 2 and CH 2 CH 2 CH 2 each group optionally substituted with 1-2 CH 3 R 4 is selected from the group H and C 3 -C 6 trialkylsilyl; or R 4 is selected from the group C 1 -CIO alkyl, C 2 -C 10 alkenyl, C 2 -Co 10 alkynyl, C 1 -CO 10 alkoxy, CI-CIO alkylthio, phenyl, phenoxy, phenylthio and naphihyl, each group optionally substituted with 1-3 substituents independently selected from WI; R 5 and R 6 are independently selected from the group CI-C 10 alkyl, C 2 -C 10 alkenyl, C 2 -CIO alkyny, C 1 -CO 10 alkoxy, C 1 -Cl 0 alkylthio, phenyl, phenoxy, phenylthio and naphthyl, each group optionally substituted with 1-3 substituents independently selected from W 1 OH; and C 3 -C 6 trialkylsilyl; R 7 is selected from the group H, NH 2 OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, Cl-C 4 alkylamino, C 2 -C 8 dialkylamino and phenyl optionally substituted with 1-3 substituents independently selected from W 1 R 8 is H; or R 8 is selected from the group C 1 -CIO alkyl, C 2 -CO 10 alkenyl, C 2 -C 1 0 alkynyl, Cl-CO 10 alkoxy, phenoxy, phenyl and naphthyl, each group optionally substituted with 1-3 substituents independently selected from W 1 R 9 and R 10 are independently selected from the group C 1 -CO 10 alkyl, C 2 -C 1 0 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 alkoxy, phenoxy, phenyl and naphthyl, each group optionally substituted with 1-3 substituents independently selected from W 1 and OH; R 1 is selected from the group H, NH 1 OH, CI-C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, CI-C 2 alkylthio, CI-C 4 alkylamnino, C 2 -C 8 dialkylamino and phenyl optionally substituted with 1-3 substituents independently selected from W 1 W is selected from the group halogen, CN, NO 2 OH, C 1 -C 6 aikyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy and CI-C 6 haloalkoxy; and W 1 is selected from the group halogen, CN, NOZ 2 C-C 2 alkyl, CI-C 2 haloalkyl, CI-C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 2 alkylthio, C 1 -C 2 haloalkylthio, C 1 -C alkylsulfonyl, C -C 2 haloalkylsulfonyl, C 1 -C 4 alkylamino, C2-C 8 dialkylamino and C 3 -C 6 trialkylsilyl.

2. A compound according to Claim 1 wherein: A is C 1 -C 6 alkylene; R 1 is C 1 -C 3 alkyl substituted with a 5- or 6-membered aromatic ring, attached through carbon or nitrogen, containing 1 to 4 heteroatoms independently selected from the group 0-4 nitrogen, 0-1 oxygen, and 0-1 sulfur, the ring optionally substituted with 1-3 substituents independently selected from W 1 r~l~l _qC 7i- WO 95/21846 PCT/US95/0 i 616 66 R 4 is selected from the group C 1 -C 1 o alkyl and phenyl, each group optionally substituted with 1-3 substituents independently selected from W 1 R 5 and R 6 are independently selected from the group CI-C 10 alkyl and phenyl, each group optionally substituted with 1-3 substituents independently selected from W 1 and W 1 is selected from the group halogen and C 1 -C 2 haloalkyl.

3. A compound according to Claim 2 wherein: X is Si; R 1 is CH 2 substituted with pyridyl, thiazole or isoxazole, the ring optionally substituted with 1-2 halogen or 1-2 methyl; R 2 and R 3 are taken together as CH 2 CH 2 or CH 2 CH 2 CH 2 each group optionally substituted with 1-2 CH 3 and R 4 R 5 and R 6 are C 1 -C 3 alkyl, CI-C 3 alkoxy and phenyl.

4. A compound according to Claim 2 wherein: X is Si; R 1 is CH 2 substituted with pyridyl, thiazole or isoxazole, the ring optionally substituted with 1-2 halogen; R 2 is selected from the group H and CI-C 3 alkyl; and R 4 R 5 and R 6 are C 1 -C 3 alkyl, CI-C 3 alkoxy and phenyl. A compound according to Claim 3 which is: 1-[(6-chloro-3-pyridinyl)methyl]- 1,2,3,5,6,7-hexahydro-2-methyl-8- nitro-6-[(trimethylsilyl)methyl]imidazo[ 1,2-c]pyrimidine.

6. A compound according to Claim 3 which is: 1-[(6-chloro-3-pyridinyl)methyl]- 1,2,3,5,6,7-hexahydro-8-nitro- 6-[(trimethylsilyl)methyl]imidazo[1,2-c]pyrimidine.

7. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to Claim 1 and a carrier therefor.

8. A method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound according to Claim 1. i -'IF i INTERNATIONAL SEARCH REPORT I Application No Inton nal Application No PCT/US 95/01616 A. CLASSIFICATION OF SUBJECT MATTER IPC 6 C07F7/08 C07F7/30 A01N55/00 According to International Patent Classification (IPC) or to both natonal classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) IPC 6 C07F A01N Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulted during the international search (name of data base and, where practical, search terms used) C. DOCUMENTS CONSIDERED TO BE RELEVANT Category Citaton of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A EP,A,O 247 477 (BAYER AG) 2 December 1987 1 see the whole document US,A,4 831 036 (WOLF, H. ET AL.) 16 May 1989 cited in the application O Further documents are listed in the continuation of box C. j Patent family members are listed in annex. Special categories of cited documents: T' later document published alter the mtemational filing date Sdocument dein the eral state of the art whch ior priority date and not in conflict with the aplication but A n document defining the general stat e of th art which s notted to understand the principle or theory underlying the considered to be of particular relevance invention earlier document but published on or after the international X document or particular relevance; the claimed invention filing date cannot be considered novel or cannot be considered to document which may throw doubts on pnonty claim(s) or involve an inventive step when the document is taken alone which is ated to establish the publication date of another document of particular relevance; the claimed invention citation or other special reason (as specified) cannot be considered to involve an inventive step when the O0' document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- other means ments, such combination being obvious to a person sdlled document published pnor to the international filing date but in the art. later than the pnority date claimed document member of the same patent family Date of the actual completion of the international search Date of mailing of the international search report 18 April 1995

24. 05.95 Name and mailing address of the ISA Authorzed officer European Patent Office, P.B. 5818 Patentlaan 2 NL 2280 HV Rijswilk Tel (+31-70) 340-2040, Tx. 31 651 ponl, Rinkel Fax 3170) 340-3016 ne, L Form PCT/ISAS/2I (secend shoet (July IY)] ~c I INTERNATIONAL SEARCH REPORT' Fn ul Application No IPCT/US 95/01616 Patent document I Publication IPatent family Publication cited in search report date member(s) f dame EP-A-0247477 02-12-87 DE-A- 3638121 03-12-87 AU-B- 597375 3 1-05-90 AU-A- 7368187 10-12-87 JP-A- 62292765 19-12-87 US-A- 4831036 16-05-89 US-A-4831036 16-05-89 DE-A- 3638121 03-12-87 AU-B- 597375 31-05-90 AU-A- 7368187 10-12-87 EP-A,B 0247477 02-12-87 JP-A- 62292765 19-12-87 IL Form PCr/ISA/21 0 (psCOL family annax) (July 1992)