JPH0210133B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel cyclohexane derivative having excellent effects as a pharmaceutical; a method for producing the same; and a pharmaceutical containing the same. For more details, see the general formula [In the formula, R means an unsubstituted or substituted phenyl group or a furyl group, and A represents the formula -(CH ₂ )-
_o (in the formula, n means an integer of 1 to 4), and X, Y, and Z are the same or different hydrogen atoms, lower alkyl group, lower alkoxy group, lower alkylcarbonyloxy group, The present invention relates to a cyclohexane derivative represented by a hydroxyl group, a lower alkylsulfonyl group, a nitro group, a cyan group, or a halogen atom; a method for producing the same; and a pharmaceutical containing the same. In the above general formula, R means an unsubstituted or substituted phenyl group or furyl group, and as a substituent for the phenyl group, a linear or branched lower alkyl group having 1 to 6 carbon atoms (e.g., methyl ,
ethyl, n-propyl, isopropyl, n-pentyl, 1-ethylpropyl, isoamyl, n-hexyl, etc.), lower alkoxy groups having 1 to 6 carbon atoms (e.g., methoxy, ethoxy, n-propoxy,
isopropoxy, n-butoxy, isobutoxy groups, etc.), hydroxyl groups, halogen atoms (e.g., chlorine, bromine,
fluorine, iodine, etc.), halogenated alkyl groups (e.g., trifluoromethyl group, etc.), amino groups, substituted amino groups (e.g., NN-dimethylamino, N-
N-diethylamino) and any adjacent carbon atom of the phenyl group with the formula -O-(CH ₂ )a-O
- (wherein a means an integer of 1 to 2), such as a methylenedioxy group, an ethylenedioxy group, etc. can be mentioned. Further, the number of substituents is one or more and may be the same or different. X, Y, and Z are the same or different hydrogen atoms, or linear or branched lower alkyl groups having 1 to 6 carbon atoms (e.g., methyl, ethyl, n-propyl, isopropyl, n-pentyl, 1-ethylpropyl , isoamyl, n-hexyl group, etc.), carbon number 1-6
Lower alkoxy groups (e.g., methoxy, ethoxy,
n-propoxy, isopropoxy, n-butoxy, isobutoxy group, etc.), lower alkylcarbonyloxy group (e.g., acetoxy, propionyloxy, valeryloxy group, etc.), hydroxyl group, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, butylsulfonyl group It means a lower alkylsulfonyl group such as a nitro group, a cyano group, or a halogen atom such as fluorine, chlorine, bromine, or iodine. Representative compounds of the present invention are listed below. (1) 2-(3-phenylpropionyl)-5-phenyl-cyclohexane-1,3-dione (2) 2-[3-(2-methoxyphenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione(3) 2-[3-(3-methoxyphenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione(4) 2-[3-(4-methoxyphenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione (5) 2-[3-(3,4-dimethoxyphenyl)
-Propionyl]-5-phenyl-cyclohexane-1,3-dione (6) 2-[3-(2,3,4-trimethoxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (7) 2-[3-(4-methylphenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione (8) 2-[3-(2-chlorophenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione (9) 2-[3-(4-chlorophenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione (10) 2-[3-(2,4-dichlorophenyl)-
Propionyl]-5-phenyl-cyclohexane-1,3-dione (11) 2-[3-(4-methylsulfonylphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (12) 2- [3-(4-cyanophenyl)-propionyl]-5-phenyl-cyclohexane-
1,3-dione (13) 2-[3-(4-hydroxyphenyl)
-Propionyl]-5-phenyl-cyclohexane-1,3-dione (14) 2-[3-(3-hydroxyphenyl)
-Propionyl]-5-phenyl-cyclohexane-1,3-dione (15) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (16 ) 2-[3-(2-hydroxy-3-methoxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (17) 2-[3-(3,4-diacetoxyphenyl) -Propionyl]-5-phenyl-cyclohexane-1,3-dione (18) 2-[3-(2-fluorophenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (19) 2- [3-(4-ethoxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione (20) 2-[3-(4-propoxyphenyl)-
Propionyl]-5-phenyl-cyclohexane-1,3-dione (21) 2-[3-(4-methoxyphenyl)-propionyl]-5-(4-methoxyphenyl)
-Cyclohexane-1,3-dione (22) 2-[3-(4-chlorophenyl)-propionyl]-5-(4-methoxyphenyl)-
Cyclohexane-1,3-dione (23) 2-[3-(2-chlorophenyl)-propionyl]-5-(4-methoxyphenyl)-
Cyclohexane-1,3-dione (24) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(4-methoxyphenyl)-cyclohexane-1,3-dione (25) 2 -(3-phenylpropionyl)-5-
(4-methoxyphenyl)-cyclohexane-
1,3-dione (26) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(2-methoxyphenyl)-cyclohexane-1,3-dione (27) 2-( 3-phenylpropionyl)-5-
(2-methoxyphenyl)-cyclohexane-
1,3-dione (28) 2-[3-(2-chlorophenyl)propionyl]-5-(4-chlorophenyl)-cyclohexane-1,3-dione (29) 2-[3-(2,3,4 -trimethoxyphenyl)-propionyl]-5-(4-chlorophenyl)-cyclohexane-1,3-dione (30) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-( 4-methylphenyl)-cyclohexane-1,3-dione (31) 2-(3-phenylpropionyl)-5-
(4-methylphenyl)-cyclohexane-1,
3-dione (32) 2-[3-(2-chlorophenyl)-propionyl]-5-(4-methylphenyl)-cyclohexane-1,3-dione (33) 2-(3-phenylpropionyl)-5-
(3,4-methylenedioxyphenyl)-cyclohexane-1,3-dione (34) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(3,4-methylenedioxyphenyl)-cyclohexane-1,3-dione (34) oxyphenyl)-cyclohexane-
1,3-dione(35) 2-(3-phenylpropionyl)-5-
(3-hydroxyphenyl)-cyclohexane-1,3-dione (36) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(3-hydroxyphenyl)-cyclohexane-1 ,3-dione(37) 2-(3-phenylpropionyl)-5-
(4-hydroxyphenyl)-cyclohexane-1,3-dione (38) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(4-hydroxyphenyl)-cyclohexane-1 ,3-dione(39) 2-(3-phenylpropionyl)-5-
(3,4-dihydroxyphenyl)-cyclohexane-1,3-dione (40) 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-(3,4-dihydroxyphenyl) enyl)-cyclohexane-1,
3-dione (41) 2-phenylacetyl-5-phenyl-cyclohexane-1,3-dione (42) 2-(4-chlorophenylacetyl)-5
-Phenyl-cyclohexane-1,3-dione (43) 2-(2-chlorophenylacetyl)-5
-Phenyl-cyclohexane-1,3-dione (44) 2-(2,4-dichlorophenylacetyl)-5-phenyl-cyclohexane-1,3
-Dione (45) 2-(4-methoxyphenylacetyl)-
5-phenyl-cyclohexane-1,3-dione (46) 2-(4-methylphenylacetyl)-5
-Phenyl-cyclohexane-1,3-dione (47) 2-(2-nitrophenylacetyl)-5
-Phenyl-cyclohexane-1,3-dione (48) 2-(2-methoxyphenylacetyl)-
5-phenyl-cyclohexane-1,3-dione (49) 2-(4-benzyloxyphenylacetyl)-5-phenyl-cyclohexane-1,3
-Dione (50) 2-(4-hydroxyphenylacetyl)-5-phenyl-cyclohexane-1,3
-Dione (51) 2-(2-benzyloxyphenylacetyl)-5-phenyl-cyclohexane-1,3
-Dione (52) 2-(2-hydroxyphenylacetyl)-5-phenyl-cyclohexane-1,3
-Dione (53) 2-(2,3,4-trimethoxyphenylacetyl)-5-phenyl-cyclohexane-
1,3-dione (54) 2-(2-benzyloxy-3-methoxyphenylacetyl)-5-phenyl-cyclohexane-1,3-dione (55) 2-(2-hydroxy-3-methoxyphenyl acetyl)-5-phenyl-cyclohexane-1,3-dione (56) 2-phenylacetyl-5-(4-chlorophenyl)-cyclohexane-1,3-dione (57) 2-(2,4-dichlorophenyl) enylacetyl)-5-(4-chlorophenyl)-cyclohexane-1,3-dione(58) 2-(4-methoxyphenylacetyl)-
5-(4-chlorophenyl)-cyclohexane-1,3-dione (59) 2-(4-methylphenylacetyl)-5
-(4-chlorophenyl)-cyclohexane-
1,3-dione(60) 2-(2-chlorophenylacetyl)-5
-(4-chlorophenyl)-cyclohexane-
1,3-dione (61) 2-(2,4-dichlorophenylacetyl)-5-(2-furyl)-cyclohexane-
1,3-dione(62) 2-(4-chlorophenylacetyl)-5
-(2-furyl)-cyclohexane-1,3-
Dione (63) 2-(2-chlorophenylacetyl)-5
-(2-furyl)-cyclohexane-1,3-
Dione (64) 2-(4-methoxyphenylacetyl)-
5-(2-furyl)-cyclohexane-1,3
-Dione (65) 2-(4-methylphenylacetyl)-5
-(2-furyl)-cyclohexane-1,3-
Dione (66) 2-(2-nitrophenylacetyl)-5
-(2-furyl)-cyclohexane-1,3-
Dione (67) 2-(4-phenylbutyryl)-5-phenyl-cyclohexane-1,3-dione(68) 2-[4-(2,4-dihydroxyphenyl)-butyryl]-5-phenyl-cyclohexane -1,3-dione (69) 2-(5-phenylvaleryl)-5-phenyl-cyclohexane-1,3-dione (70) 2-[5-(4-methoxyphenyl)-
Valeryl]-5-phenyl-cyclohexane-
1,3-dione (71) 2-(3-phenylpropionyl)-5-
(3,4-dichlorophenyl)-cyclohexane-1,3-dione (72) 2-(3-phenylpropionyl)-5-
(4-Butoxyphenyl)-cyclohexane-
1,3-dione(73) 2-(3-phenylpropionyl)-5-
(4-dimethylaminophenyl)-cyclohexane-1,3-dione (74) 2-(3-phenylpropionyl)-5-
(4-diethylaminophenyl)-cyclohexane-1,3-dione (75) 2-(3-phenylpropionyl)-5-
(3,4-ethylenedioxyphenyl)-cyclohexane-1,3-dione (76) 2-[3-(4-ethylsulfonylphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione Note that the compound [] obtained in the present invention can be considered to be various ketoenol type compounds based on its structure, such as the following compound [a] or [a′]. (In the formula, R, A, X, Y, Z have the above-mentioned meanings), but since these are substantially the same substance, it goes without saying that they are included in the compounds of the present invention. . The pharmaceutically acceptable salt of the compound of the present invention [] may be any commonly used non-toxic salt, and specifically includes, for example, alkali metal salts such as sodium salts and potassium salts, calcium salts, Examples include alkaline earth metal salts such as magnesium salts, organic amine salts such as iron salts, ammonium salts, trimethylamine salts, triethylamine salts, ethanolamine salts, diethanolamine salts, pyridine salts, and dicyclohexylamine salts. The cyclohexane derivatives provided by the present invention are all new compounds that have not been described in any literature,
It is a compound with extremely low toxicity, a remarkable hypotensive effect, and a long-lasting effect. That is, the compound group of the present invention has renal, endocrine,
It is useful for the prevention and treatment of various types of hypertension, including cardiovascular, neurological, and essential hypertension. Hypertension is a typical adult disease along with cancer, heart disease, etc., and the number of patients has been increasing markedly in recent years as the number of elderly people has increased. However, since the causes of hypertension are diverse, there is currently no definitive treatment method, although various antihypertensive drugs are used. Furthermore, when hypertensive patients take antihypertensive drugs, they are forced to take them continuously due to the nature of the disease, so it is important to find drugs that are not only highly effective, but also have long-lasting effects and are highly safe with no side effects. Development is desired. The inventors of the present invention have conducted extensive research based on the demands in the medical field, and have discovered that the present invention has excellent pharmacological effects that satisfy the above conditions. That is, the compound of the present invention [] and its salts gradually and reliably exert a blood pressure lowering effect, and also have an excellent long-lasting effect, so that they can be used as extremely useful blood pressure lowering agents. It is particularly useful in the treatment of essential hypertension, whose cause is unknown. The compounds of the present invention [ ] and salts thereof are also useful as antibacterial agents against Gram-positive bacteria, Gram-negative bacteria, and fungi. The compound of the present invention [] can be produced by various methods, and one of the commonly used methods is as follows. (1) Production method A: When A of the target compound [ ] is represented by the formula - (CH ₂ ) _o -, that is, the general formula The compound represented by can also be produced by the method shown below. (In the formula, B means a halogen atom, R and n
has the meaning given above. ) That is, the compound represented by the general formula [] and the compound represented by the general formula [] are reacted to obtain the compound [b] of the present invention. This reaction can be carried out without solvent or with dimethylformamide.
Benzene, toluene, xylene, etc.
A solvent that does not participate in the reaction can be appropriately selected and used from ether solvents such as ethyl ether and tetrahydrofuran, halogen solvents, and the like.
Although the reaction proceeds at room temperature, it is preferable to heat the reaction to the boiling point of the solvent. The reaction can be carried out more smoothly by adding a catalyst such as triethylamine, alkali bicarbonate, alkali carbonate, or pyridine to the reaction system. In this case, the amount of catalyst used is preferably at least twice the mole of the starting material. (2) Production method B: Among the target compounds [b], when n=2 or 4, it can also be produced by the following method. (In the formula, R, X, Y, and Z have the above-mentioned meanings.) That is, a compound represented by the general formula [] is reacted with a compound represented by the general formula [] to form a compound represented by the general formula []. This is then reduced to obtain the compound [b] of the present invention. When reacting a compound represented by the general formula [] with a compound represented by the general formula [],
In the presence of an acid such as hydrogen chloride, boron trifluoride, or a base catalyst such as piperidine, morpholine, pyrrolidine, sodium hydroxide, or a mixture thereof, without solvent or with a lower alcohol such as methanol, ethanol, propanol, isopropanol, etc. , benzene, toluene, xylene, and the like; ethers such as ethyl ether and tetrahydrofuran; and halogenated alkyl solvents such as chloroform and dichloroethane. Solvents that do not participate in the reaction can be appropriately selected and used. Although the reaction proceeds at room temperature, it is preferable to heat the reaction to the boiling point of the solvent. Note that the reaction can proceed more smoothly by removing water generated during the reaction from the reaction system. When reducing the compound represented by the general formula [] obtained in this way to obtain the compound [b] of the present invention, a solvent such as alcohol, ether, or acetic acid may be selected as appropriate, and palladium, - Reduction is carried out under pressure or 1 atm in the presence of a catalyst such as nickel or platinum oxide to obtain the compound [b] of the present invention. In this production method, when reacting the compound represented by the general formula [] with the compound represented by the general formula [], when using a secondary amine such as piperidine, morpholine, or pyrrolidine among the above-mentioned base catalysts, Enamine type compounds are produced. Specifically, in the case of the above-mentioned secondary amine, an enamine type compound [] represented by the following formula is obtained. [In the formula, R, X, Y, Z and n have the above-mentioned meanings, and B is a group represented by the formula -(CH ₂ ) ₄ -,
A group represented by (CH ₂ ) ₅ -- or --(CH ₂ ) ₂ --O
--(CH ₂ ) ₂ ^-- means a group represented by -. ] In this case as well, the compound [b] of the present invention can be obtained by reducing the compound [] in exactly the same manner as in the above-mentioned case. Next, the excellent pharmacological effects of the compounds of the present invention will be explained below with respect to representative compounds of the present invention. 1 Blood pressure lowering effect 1 group of 6 spontaneously hypertensive rats (hereinafter referred to as
SHR) (approx. 30 weeks old, systolic blood pressure 230 mmHg)
(before and after), the test compound suspended in gum arabic suspension was orally administered at a rate of 10 mg/Kg once a day for 2 days. Blood pressure was measured using a Shimadzu continuous blood pressure measuring device SCS-301 (manufactured by Shimadzu Corporation) before and 6 hours after administration, and systolic blood pressure was measured non-invasively from the artery at the tail of the SHR under anesthesia. . Note that only the aqueous gum arabic solution was administered to the animals in the control group. The experimental results are shown in Table 1.

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[Table] As shown in Table 1, a clear drop in blood pressure was observed for the series of compounds of the present invention 6 hours after administration, while in the control group, the blood pressure was 245 ± 5 mmHg before the start of administration, but there was little change during the 2-day dosing period. did not show. Thus, it is clear that the compounds of the present invention have extremely excellent antihypertensive effects, and are particularly useful as antihypertensive agents for essential hypertension. 2 Acute toxicity SD rat (weight: 160g to 280g, approximately 8 weeks old)
5 animals were used in each group. After administering the compound of the present invention, we observed life and death for 14 days.
LD50 is shown in Table 2.

[Table] Examples are shown below to explain the present invention in more detail, but it goes without saying that the present invention is not limited thereto. Example 1 2-[3-(3,4-dihydroxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3-dione 2-[3-(3,4-dibenzyloxyphenyl)- Dissolve 4 g of [propenoyl]-5-phenyl-cyclohexane-1,3-dione in 100 ml of tetrahydrofuran and 3 g of 5% palladium-carbon catalyst.
and catalytic reduction at normal pressure. The title 2-[3-
(3,4-dihydroxyphenyl)-propionyl]-5-phenyl-cyclohexane-1,3
- Obtain 1.2 g of dione (yield 45%). Melting point: 225-226°C Elemental analysis value: C ₂₁ H ₂₀ O ₅ C H Theoretical value (%) 71.58 5.72 Actual value (%) 71.51 5.83 IR: (cm ^-1 , Nudyol) 3510, 1640, 1540 NMR: δ (brom TMS) 2.6~3.4 (9H, m),
6.3~6.65 (3H, m), 7.28 (5H, s),
8.53 (1H, s), 8.64 (1H, s), 17.95
(1H,s) (disappeared with D ₂ O) Example 2 2-Phenylacetyl-5-phenyl-cyclohexane-1,3-dione 1.9 g of 5-phenyl-cyclohexane-1,3-dione was mixed with 30 ml of dry dimethyl formaldehyde. of phenylacetyl chloride, then add 3.4 ml of triethylamine and cool with ice (0°C) to dissolve phenylacetyl chloride.
Drop 1.7g. After dropping, stir at room temperature for 30 minutes, then pour into 100ml of water.
Adjust the pH to 2-3 with 2N hydrochloric acid and extract with benzene.
After treatment with silica gel chromatography (solvent: benzene), recrystallization from isopropyl alcohol yields the title 2-
0.8 g (yield 26%) of phenylacetyl-5-phenyl-cyclohexane-1,3-dione is obtained. Melting point: 100-100.5°C Elemental analysis value: As C ₂₀ H ₁₈ O ₃ C H Theoretical value (%) 78.41 5.92 Actual value (%) 79.01 6.13 IR: (cm ^-1 , Nujiol) 1665, 1560, 1500,
1295 NMR: δ (brom TMS) 2.6-3.6 (5H, m),
4.38 (2H, s), 7.27 (10H, s), 17.96
(1H,s) (disappeared with D ₂ O) Example 3 2-(4-benzyloxyphenylacetyl)
-5-Phenyl-cyclohexane-1,3-dione Dissolve 9.4 g of 5-phenyl-cyclohexane-1,3-dione in 150 ml of dry dimethylformamide, then add 10 ml of triethylamine and cool on ice (-5°C) to dissolve 4- 16 g of benzyloxyphenylacetyl chloride is added dropwise. After the addition is complete, stir at room temperature for 30 minutes, add 150 ml of benzene, then pour into 200 ml of 2N hydrochloric acid and stir at room temperature for 30 minutes. After separating the benzene layer, 100ml
The extract was extracted twice with benzene, washed with water, dried over magnesium sulfate, and distilled off. Separated by silica gel chromatography (benzene solvent), recrystallized from n-propyl alcohol, and then recrystallized from n-hexane to obtain the title 2-(4-benzyloxyphenylacetyl)-
5-phenyl-cyclohexane-1,3-dione
Obtain 3.4 g (yield 18%). Melting point: 115-116°C Elemental analysis value: as C ₂₇ H ₂₄ O ₄ C H Theoretical value (%) 78.62 5.86 Actual value (%) 78.72 5.83 IR: (cm ^-1 , Nujiol) 1665, 1560, 1515,
1253 NMR: δ (brom TMS) 2.55-3.6 (5H, m),
4.33 (2H, s), 5.0 (2H, s), 6.86 (2H,
d, J=9Hz), 7.1~7.4 (12H, m),
17.96 (1H, s) (disappeared with D ₂ O) Example 4 2-(4-hydroxyphenylacetyl)-
5-phenyl-cyclohexane-1,3-dione 2-(4-benzyloxyphenylacetyl)
2 g of -5-phenyl-cyclohexane-1,3-dione was dissolved in 80 ml of tetrahydrofuran, 1 g of 5% palladium-carbon catalyst was added, and catalytic reduction was carried out under 1 atmosphere at room temperature for 4 hours. The catalyst was filtered, concentrated, recrystallized from benzene, separated by a column, and recrystallized from benzene to obtain the title 2-(4-hydroxyphenylacetyl)-5-phenyl-cyclohexane-
0.8 g (yield 51%) of 1,3-dione is obtained. Melting point: 168-168.5°C Elemental analysis value: C ₂₀ H ₁₈ O ₄ C H Theoretical value (%) 74.52 5.63 Actual value (%) 74.62 5.93 IR: (cm ^-1 , Nudyol) 3190, 1640, 1550 NMR: δ (brom TMS) 2.6~3.6 (5H, m),
4.18 (2H, s), 6.64 (2H, d, J=8
Hz), 6.95 (2H, d, J=8Hz), 7.19
(5H, s), 9.15 (1H, s), 17.95 (1H,
s) (Disappears with D ₂ O) Example 5 (Reference example) 2-(4-chlorophenyl)carbamoyl-5
-Phenyl-cyclohexane-1,3-dione Dissolve 3.76 g of 5-phenyl-cyclohexane-1,3-dione in 50 ml of dry dimethyl formaldehyde, add 0.3 ml of triethylamine, and add 3.48 g of 4-chlorophenyl isocyanate dropwise at room temperature. . After stirring at room temperature for 1 hour, pour into 100 ml of water to collect crystals, wash with water, and add 30 ml of ethanol to chloroform.
Recrystallize from 20 ml to obtain 3.8 g (yield 56%) of the title 2-(4-chlorophenyl)carbamoyl-5-phenyl-cyclohexane-1,3-dione. Melting point: 155-156°C Elemental analysis value: C ₁₉ H ₁₆ ClNO ₃ C H N Theoretical value (%) 66.77 4.72 4.10 Actual value (%) 66.60 4.73 4.06 IR: (cm ^-1 , Nujiol) 1640, 1600, 1550 ，
813 NMR: δ (brom TMS) 2.6-3.5 (5H, m),
7.25 (5H, s), 7.09 (2H, d, J=9
Hz), 7.33 (2H, d, J = 9Hz), 11.87
(1H, s) (disappeared with D ₂ O) Examples 6 to 84 Examples 6 to 44 were carried out by the method of Example 1, Examples 45 to 69 were carried out by the method of Example 2, and Examples 70 to 79 were carried out by the method of Example 2. In the method of Example 5 (reference example),
The compounds shown in Table 3 below were obtained by the respective methods. In addition, Examples 68 to 79 among the above-mentioned Examples are shown as reference examples.

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[Table] When using the compound of the present invention [ ] and its salt as a hypotensive agent for the treatment of various hypertension such as essential hypertension, renal hypertemia, and malignant hypertension,
It is administered orally or parenterally (intramuscularly, subcutaneously, intravenously, suppositories, etc.). The dosage varies depending on the patient's weight, age, symptoms, administration method, etc., but is usually 10 to 1500 mg per day for adults. In order to formulate a compound of the present invention, it is formed into a dosage form such as a tablet, granule, powder, capsule, injection, suppository, etc. by a conventional method in the field of pharmaceutical preparation. That is, when preparing oral solid preparations, excipients are added to the main drug, and if necessary, binders, disintegrants,
After adding a lubricant, coloring agent, and flavoring agent, it is made into tablets, coated tablets, granules, powders, and capsules by conventional methods. Examples of excipients include lactose, cornstarch,
Examples of binders include sucrose, glucose, sorbitol, crystalline cellulose, etc., and examples of binders include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth,
Examples of disintegrating agents include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, calcium citrate, dextrin, and pectin. , carboxymethyl cellulose calcium salts, etc., lubricants such as magnesium stearate, talc, polyethylene glycol, silica hydrogenated vegetable oil, etc., coloring agents that are permitted to be added to pharmaceuticals, and flavoring agents. For example, cocoa powder, peppermint, aromatic acid, peppermint oil, dragonbrain, cinnamon powder, etc. are used. Of course, these tablets and granules may be coated with sugar coating, gelatin coating, or other coatings as appropriate. In addition, when preparing a liquid preparation for oral use, a flavoring agent, a buffering agent, a stabilizer, etc. can be added to the main drug as necessary, and a syrup or the like can be prepared by a conventional method. When preparing injections, add as necessary to the main drug.
Add PH adjusting agents, buffering agents, suspending agents, solubilizing agents, stabilizers, isotonic agents, preservatives, etc., and prepare subcutaneous, intramuscular, or intravenous injections using conventional methods. Suspending agents include, for example, methyl cellulose,
Polysorbate 80, hydroxyethyl cellulose, gum arabic, tragacanth powder, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, etc., and solubilizing agents include polyoxyethylene hydrogenated castor oil, polysorbate 80, nicotinamide, polyoxyethylene sorbitan. Monolaurate, magrogol, castor oil fatty acid ethyl ester, etc. are used as stabilizers, sodium sulfite, sodium metasulfite, ether, etc. are used as preservatives.
Methyl paraoxybenzoate, ethyl paraoxybenzoate, sorbic acid, phenol, cresol,
Examples include chlorocresol. Next, in order to explain the present invention in more detail, one formulation example will be given, but it goes without saying that the present invention is not limited thereto. Formulation example 1 Tablets 5-phenyl-2-phenylacetyl-cyclohexane-1,3-dione 100g Cornstarch 10g Papilla 20g Carboxymethylcellulose calcium 15g Microcrystalline cellulose 40g Polyvinylpyrrolidone 5g Talc 10g Weighed using the above recipe in a conventional manner It was made into a 200mg tablet. Formulation Example 2 Capsule 2-(4-chlorophenyl)carbanoyl-
5-phenyl-cyclohexane-1,3-dione 100g nipple 100g per capsule by the usual method according to the above recipe
200mg was filled into hard capsules.

Claims (1)

[Claims] 1. General formula [In the formula, R means an unsubstituted or substituted phenyl group or a furyl group, and A is the formula -(CH ₂ ) _o
- (in the formula, n means an integer of 1 to 4), X, Y, Z are the same or different hydrogen atoms, lower alkyl group, lower alkoxy group, lower alkylcarbonyloxy group, a hydroxyl group, a lower alkylsulfonyl group, a nitro group, a cyano group, or a halogen atom] and salts thereof. 2 formulas Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 3 formulas Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 4 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 5 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 6 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 7 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 8 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 9 formula Cyclohexane derivatives and salts thereof according to claim 1, which are represented by: 10 General formula (In the formula, R means an unsubstituted or substituted phenyl group or furyl group) For a compound represented by the general formula (In the formula, B means a halogen atom, and n is 1 to 4
X, Y, Z are the same or different hydrogen atoms, lower alkyl groups, lower alkoxy groups,
It is characterized by reacting a compound represented by a lower alkylcarbonyloxy group, a hydroxyl group, a lower alkylsulfonyl group, a nitro group, a cyano group, or a halogen atom. general formula (In the formula, R, n, X, Y, and Z have the above-mentioned meanings.) A method for producing a cyclohexane derivative represented by the following. 11 General formula Or general formula (In the formula, R means an unsubstituted or substituted phenyl group or a furyl group, and X, Y, and Z are the same or different hydrogen atoms, lower alkyl group, lower alkoxy group, lower alkylcarbonyloxy group, hydroxyl group, lower alkylsulfonyl group, nitro group, cyano group, or halogen atom) is reduced to form a compound represented by the general formula Or general formula A method for producing a cyclohexane derivative, which comprises obtaining a cyclohexane derivative represented by the formula (wherein R, X, Y, and Z have the above-mentioned meanings). 12 General formula (wherein R means an unsubstituted or substituted phenyl group or furyl group), a compound represented by the general formula Or general formula (In the formula, X, Y, Z are the same or different hydrogen atoms,
lower alkyl group, lower alkoxy group, lower alkylcarbonyloxy group, hydroxyl group, lower alkylsulfonyl group, nitro group, cyano group, or halogen atom). Or general formula (In the formula, R, X, Y, and Z have the above-mentioned meanings) A compound represented by the following is obtained, and this compound is then reduced to obtain the general formula Or general formula (In the formula, R, X, Y, and Z have the above-mentioned meanings.) A method for producing a cyclohexane derivative, characterized by obtaining a cyclohexane derivative represented by the following. 13 General formula [In the formula, R means an unsubstituted or substituted phenyl group or a furyl group, and A is the formula -(CH ₂ ) _o
- (in the formula, n means an integer of 1 to 4), X, Y, Z are the same or different hydrogen atoms, lower alkyl group, lower alkoxy group, lower alkylcarbonyloxy group, A cyclohexane derivative represented by a hydroxyl group, a lower alkylsulfonyl group, a nitro group, a cyano group, or a halogen atom, or a salt thereof, as an active ingredient.