AU611566B2 - New process for the preparation of n-(23-vinblastinoyl) derivatives of 1-amino-methyl-phosphonic acid - Google Patents
New process for the preparation of n-(23-vinblastinoyl) derivatives of 1-amino-methyl-phosphonic acid Download PDFInfo
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- AU611566B2 AU611566B2 AU36200/89A AU3620089A AU611566B2 AU 611566 B2 AU611566 B2 AU 611566B2 AU 36200/89 A AU36200/89 A AU 36200/89A AU 3620089 A AU3620089 A AU 3620089A AU 611566 B2 AU611566 B2 AU 611566B2
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- 238000000034 method Methods 0.000 title claims description 15
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical class NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 4
- -1 arylalkyl radical Chemical class 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 8
- OOQPJZVJXMBXDG-BWXJFNBNSA-N vinblastinoic acid Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C(C45[C@H]([C@@](C(OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(O)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 OOQPJZVJXMBXDG-BWXJFNBNSA-N 0.000 claims description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 101000830713 Homo sapiens Torsin-3A Proteins 0.000 claims description 2
- 102100024603 Torsin-3A Human genes 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- UIBCDEFKKLRXHR-UHFFFAOYSA-N diethoxyphosphorylmethanamine Chemical compound CCOP(=O)(CN)OCC UIBCDEFKKLRXHR-UHFFFAOYSA-N 0.000 description 2
- 239000012156 elution solvent Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical class C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- DGSLPJDIFKVSIB-UHFFFAOYSA-N (1-azaniumyl-2-methylpropyl)-hydroxyphosphinate Chemical compound CC(C)C(N)P(O)(O)=O DGSLPJDIFKVSIB-UHFFFAOYSA-N 0.000 description 1
- UUSMBCSSWVSVGA-UHFFFAOYSA-N 1-diethoxyphosphoryl-2-methylpropan-1-amine Chemical compound CCOP(=O)(OCC)C(N)C(C)C UUSMBCSSWVSVGA-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
COMMONWEALTH OF AUSTRALIA An~ Fr PATENTS ACT 1952-69 COMPLETE SPECIFICATION
(ORIGINAL)
Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Int. Class IVr~rity: *Relted Art: *0 0 0 fanje of Applicant: Address of Applicant: ADIR ET COMPAGNIE 22 Rue Garmier, F-92201 Neuilly Sur Seine, France Actual Inventor: GILBERT LAVIELLE and PATRICK HAUTEFAYE 5.
S
Address for Service =WWW~iX VWatermark Patent Trademark Attorneys 50 QUEEN STREET, MELBOURNE, AUSTRALIA, 3000.
Complete Specification for the invention entitled: NEW PROCESS FOR THE PREPARATION OF N-(23-VINBLASTINOYL) DERIVATIVES OF 1-AMINO-METHYL-PHOSPHONIC ACID The following statement is a full description of this invention, including the best method of performing it known to us 1 00 a 4 00 0 0
*.S
S.
S
'4 SO0 -4 5 744 The present invention relates to a new process for preparing N-(23-vinblastinoyl) derivatives of 1aminomethylphosphonic acid.
Some N-(23-vinblastinoyl) derivatives of 1aminomethylphosphonic acid are described in French Patent Application No. 87/16,327. The compounds claimed possess much greater antitumor activity than all known vinblastine derivatives. According to the preparation process described in the application referred to above, the bisindole derivatives are obtained by condensation of the appropriate aminophosphonates with 3-decarbomethoxy-4-0deacetylvinblastine-3-carboxazide. This azide is prepared from vinblastine by hydrazinolysis followed by nitrosation, which necessitates the use of anhydrous hydrazine, 15 a very dangerous and toxic reagent.
Belgian Patent No. 904,064 describes a process for preparing some N-(23-vinblastinoyl) derivatives of aminoacids and peptides by the mixed anhydride method.
However, this process is of little industrial importance, 20 since it necessitates at least two separate preparation stages.
The Applicant has now discovered a new process for preparing N-(23-vinblastinoyl) derivatives of 1aminomethylphosphonic acid which is very advantageous 25 compared with the already known processes.
In effect, this process enables the derivatives of general formula I to be obtained from vinblastinoic acid in a single stage and in good yield, and the reagents used are commercially available, inexpensive and easy to handle.
The subject of the invention is, more precisely, a process for preparing the derivatives of general formula I, 2 8' 7' a S. S .a a S a
S~
CO NH -CH 23 /ORi
P
l\O 0 in which: RI denotes a hydrogen atom, a linear or branched alkyl radical containing from 1 to 6 carbon atoms, a linear or branched alkylene radical containing from 1 to 6 carbon atoms, an arylalkyl radical having 7 to carbon atoms which can bear as a substituent on the aromatic ring a halogen atom, a hydroxyl radical or an alkyl or alkoxy radical each containing from 1 to carbon atoms, a 2-indolylmethyl radical, a 4-imidazolylmethyl radical or an alkoxycarbonylmethyl radical containing from 3 to 11 carbon atoms, and
R
2 and R 3 which may be identical or different, each denote a linear or branched alkyl radical containing from 1 to 6 carbon atoms, wherein vinblastinoic acid, the compound of formula II
U
-3 71 OH 12' 6 Y io I 0' 10
(II)
CO OH 23 a. a a a.
a a a. a.
a a a a a a a.
a a a.
a a a. a is condensed with N,N'-carbonyldiimidazole, the compound of formula III: N N -N
(III)
at room temperature, in an anhydrous polar solvent such as dimethylformamide and under an inert atmosphere, then wherein an aminopho sphonate of general formula
IV:
SOR 2 R-CH P 1 11-OR 3 NH, 0
(IV)
in which R 1
R
2 and R, have the same meaning as that stated in the formula I, is introduced to react in the reaction medium, and thereafter, wherein the medium is hydrolyzed with distilled 4 water and wherein the expected compouunds of general formula I are extracted by means of a chlorinated hydrocarbon such as dichloromethane.
Vinblastinoic acid, the compound of formula II may be prepared according to the method described in French Patent Application No. 75/31,159.
N,N'-Carbonyldiimidazole is a commercially available product (Aldrich®).
The compounds of general formula IV are prepared according to the methods described in French Patent Application No. 87/16,327.
According to the process of the invention, the 15 compounds of formula I are obtained in the form of free bases.
bTo form addition salts of the compounds of general formula I, pharmaceutical acceptable organic or inorganic acids may be used. Among these acids, hydro- 99 chloric, phosphoric, fumaric, citric, oxalic, sulfuric, tartaric, maleic and methanesulfonic acids, and the like, may be mentioned.
The examples which follow, given without implied limitation, illustrate the invention.
The melting points stated are measured according to the micro-Kofler technique.
The mass spectra (F A B+ and F A are obtained with a NERMAG® 10-10C mass spectrometer with a quadripole filter.
Matrix: mixture of glycerol and thioglycerol (50:50 v/v).
Incident gas: krypton Energy: 6 to 8 keV.
EXAMPLE 1 Diethyl 4-O-deacet'.-23-vinblastinoyl) aminomethylphosphonate mg of N,N'-carbonyldiimidazole are added under argon to a solution of 100 mg of vinblastinoic acid in I_ 5 ml of anhydrous dimethylformamide. The mixture is stirred for one hour at room temperature before a solution of 100 mg of diethyl aminomethylphosphonate in 1 ml of anhydrous dimethylformamide is added. The mixture is kept stirred at room temperature and under argon for 24 hours. The medium is hydrolyzed by means of 25 ml of distilled water and the product extracted by means of 3 times 25 ml of dichloromethane. The organic phases are combined, washed once with saline solution and once with water and dried over anhydrous magnesium sulfate.
After evaporation of the solvent, the residue is purified by colimn chromatography, using 170 g of Lichrosorb RP 18 (Merck®) as the stationary phase and a mixture of methanol and 0.01 M disodium phosphate (70:30 15 v/v) as the elution solvent.
~Yield: 50 Diethyl N-(4-O-deacetyl-23-vinblastinoyl)aminomethylphosphonate sulfate was obtained after adding 2 ~strength ethanolic sulfuric acid.
Melting point: 194-204 0 C (decomposition).
Mass spectrum, FAB+ 904 651, 562, 550, 355.
EXAMPLE 2 Diethyl N-(4-O-deacetyl-23-vinblastinoyl)-1- 25 amino-2-methylpropylphosphonate This compound was prepared according to the process described in Example 1, but using diethyl 1amino-2-methylpropylphosphonate instead of diethyl aminomethyl phosphonate.
The product derived from the reaction was purified, after evaporation of the solvent, on a chromatographic column, using silica (230-400 mesh) as the stationary phase and a mixture of toluene and ethanol as the elution solvent.
Yield: 35 Mass spectrum, FAB 946 709, 651.
Mass spectrum, FAB- 944 926, 916, 806, 180, 152, 137, 108.
Claims (2)
1. A process for preparing the derivatives of general formula I OH 11 8 7 12 6' N 21 13 18' CH30 8 7 14* 6 IH 5 12 5 2j 0HH CH3 R I CO NH CH S* in which: 6 carbon atoms, an arylalkyl radical having 7 to Scarbon atoms which can bear as a substituent on the aromatic ring a halogen atom, a hydroxyl radical or an alkyl or alkoxy radical each containing from 1 to carbon atoms, a 2-indolylmethyl radical, a 4-imidazolyl- methyl radical or an alkoxycarbonylmethyl radical con- taining from 3 to 11 carbon atoms, and R2 and Ratoms which may be identical or diffsubstitu erent, I- i Iriilllili "i ~r i;~iii i i 7 each denote a linear or branched alkyl radical containing from 1 to 6 carbon atoms, wherein vinblastinoic acid, the compound of formula II 8' 7' (II) 4* a a a 4 4 a 4 4 4 4 S. 4 4«
4. 44 9D 0 CO OH 23 is condensed with N,N'-carbonyldiimidazole, the compound of formula III: N N-C -N 0 (III) at room temperature, in an anhydrous polar solvent and under an inert atmosphere, then wherein an aminophosponate of general formula IV: 8 OR 2 RI-CH- P (IV) I 11'"OR3 NH 2 0 in which R 1 R 2 and R, have the same meaning as that stated in the formula I, is introduced to react in the reaction medium, and thereafter, wherein the medium is hydrolyzed with distilled water and wherein the expected compounds of general formula 10 I are extracted by means of a chlorinated hydrocarbon. 2. The process as claimed in claim 1, wherein the condensation of vinblastinoic acid with N,N'-carbonyl- *C diimidazole and an aminophosphonate of general formula IV, as claimed in claim 1, is carried out under an inert atmosphere in the presence of argon. 3. The process as claimed in claim 1, wherein the condensation of vinblastinoic acid with N,N'-carbonyl- diimidazole and an aminophosphonate of general formula IV, as claimnjd in claim 1, is carried out in a single stage. 4. The process as claimed in claim 1, wherein the condensation of vinblastinoic acid with N,N'-carbonyl- diimidazole and an aminophosphonate of general formula IV, as claimed in claim 1, is carried out in dimethyl- formamide. DATED this 8th day of June 1988 ADIR ET COMPAGNIE WATERMARK PATENT TRADEMARK ATTORNEYS QUEEN STREET MELBOURNE. VIC. 3000.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8807742 | 1988-06-10 | ||
| FR8807742A FR2632643B1 (en) | 1988-06-10 | 1988-06-10 | NOVEL PROCESS FOR THE PREPARATION OF N- (VINBLASTINOYL-23) DERIVATIVES OF 1-AMINO METHYLPHOSPHONIC ACID |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU3620089A AU3620089A (en) | 1989-12-14 |
| AU611566B2 true AU611566B2 (en) | 1991-06-13 |
Family
ID=9367142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU36200/89A Ceased AU611566B2 (en) | 1988-06-10 | 1989-06-09 | New process for the preparation of n-(23-vinblastinoyl) derivatives of 1-amino-methyl-phosphonic acid |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0346235A1 (en) |
| JP (1) | JPH0236187A (en) |
| AU (1) | AU611566B2 (en) |
| DK (1) | DK284789A (en) |
| FR (1) | FR2632643B1 (en) |
| NZ (1) | NZ229479A (en) |
| OA (1) | OA09421A (en) |
| PT (1) | PT90807A (en) |
| ZA (1) | ZA894386B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2672287B1 (en) * | 1991-01-31 | 1994-07-22 | Adir | NEW INDUSTRIAL PROCESS FOR THE PREPARATION OF N- (DESACETYL-O-4 VINBLASTINOYL-23) AMINO-1 METHYL-2 PROETYLPHOSPHONATE (1S) AND ITS SALTS. |
| US5473092A (en) * | 1992-11-20 | 1995-12-05 | Monsanto Company | Synthesis of optically-active phosphono analogs of succinates |
| FR2905949B1 (en) * | 2006-09-20 | 2008-11-21 | Pierre Fabre Medicament Sa | FLUORINE DERIVATIVES OF CATHARANTHIN, PREPARATION THEREOF AND THEIR USE AS PRECURSORS OF ALKALOIDS DIMERES DE VINCA |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU607554B2 (en) * | 1987-11-25 | 1991-03-07 | Les Laboratoires Servier | New n-(23-vinblastinoyl) derivatives of 1-aminomethyl- phosphonic acid, processes for preparing them and pharmaceutical compositions containing them |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56125335A (en) * | 1980-03-06 | 1981-10-01 | Fujisawa Pharmaceut Co Ltd | 1,4-naphthoquinone derivative, its preparation, and its use |
-
1988
- 1988-06-10 FR FR8807742A patent/FR2632643B1/en not_active Expired - Lifetime
-
1989
- 1989-06-09 ZA ZA894386A patent/ZA894386B/en unknown
- 1989-06-09 OA OA59592A patent/OA09421A/en unknown
- 1989-06-09 EP EP19890401595 patent/EP0346235A1/en not_active Withdrawn
- 1989-06-09 AU AU36200/89A patent/AU611566B2/en not_active Ceased
- 1989-06-09 NZ NZ229479A patent/NZ229479A/en unknown
- 1989-06-09 PT PT90807A patent/PT90807A/en not_active Application Discontinuation
- 1989-06-09 DK DK284789A patent/DK284789A/en not_active Application Discontinuation
- 1989-06-09 JP JP1148225A patent/JPH0236187A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU607554B2 (en) * | 1987-11-25 | 1991-03-07 | Les Laboratoires Servier | New n-(23-vinblastinoyl) derivatives of 1-aminomethyl- phosphonic acid, processes for preparing them and pharmaceutical compositions containing them |
Also Published As
| Publication number | Publication date |
|---|---|
| PT90807A (en) | 1989-12-29 |
| ZA894386B (en) | 1990-02-28 |
| NZ229479A (en) | 1990-12-21 |
| JPH0236187A (en) | 1990-02-06 |
| DK284789D0 (en) | 1989-06-09 |
| EP0346235A1 (en) | 1989-12-13 |
| OA09421A (en) | 1992-10-15 |
| AU3620089A (en) | 1989-12-14 |
| FR2632643B1 (en) | 1990-09-07 |
| FR2632643A1 (en) | 1989-12-15 |
| DK284789A (en) | 1989-12-11 |
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