EP0034473A2
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EP
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Substituted imidazoles, their preparation and pharmaceutical compositions containing the same
Assignee: Farmos Yhtyma Oy
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Filing: 1981-02-12
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Granted: —
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Expires: 2001-02-12
Abstract
Abstract The invention provides compounds of the formula: wherein each of R 1 , R 2 and R 3 , which can be the same or different is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxv, amino, hydroxy or nitro; R 4 is hydrogen or alkyl of 1 to 7 carbon atoms; X is (R 5 is hydrogen or hydroxy) and n is 1-4; and their non-toxic pharmaceutically acceptable acid addition salts. These compounds exhibitvaluable pharmacological activity and are useful in the treatment of mammals, especially as anti- hypertensive agents. Furthermore, some of the compounds have proved to possess diuretic, ß-blocking activity and/or antithrombotic activity. The compounds may be made by a variety of methods and may be incorporated in pharmaceutical compositions also comprising a compatible pharmaceutically acceptable carrier.
Inventors
- 👤 Arto Johannes Karjalainen
- 👤 Kauko Oiva Antero Kurkela
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-27 22:36
CPC Classifications
C; C07; C07D; C07D233/00; C07D233/54; C07D233/56; A; A61; A61P; A61P25/00; A61P25/02; A61P31/00; A61P31/04; A61P7/00; A61P7/02; A61P7/10; A61P9/00; A61P9/12; C07D233/64; C07D263/00; C07D263/02; C07D263/30; C07D263/32
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
133 words
A substituted imidazole of the formula: wherein each of R 1 , R 2 and R 31 which can be the same or different, is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro; R 4 is hydrogen or an alkyl radical of 1 to 7 carbon atoms; X is R 5 is hydrogen or hydroxy; and n is an integer from 1-4, provided that when n is 1 and X is -CH 2 -, R 1 , R 2 , R 3 and R 4 are not all hydrogen, and that when n is 1, X is -CH 2 -, two of R 1 , R 2 and R 3 are methoxy, and the third is hydrogen, R 4 is not methyl; and its non-toxic, pharmaceutically acceptable acid addition salts.
Claim 2
Dependent Claim
133 words
A substituted imidazole of the formula: wherein each of R 1 , R 2 and R 31 which can be the same or different, is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro; R 4 is hydrogen or an alkyl radical of 1 to 7 carbon atoms; X is R 5 is hydrogen or hydroxy; and n is an integer from 1-4, provided that when n is 1 and X is -CH 2 -, R 1 , R 2 , R 3 and R 4 are not all hydrogen, and that when n is 1, X is -CH 2 -, two of R 1 , R 2 and R 3 are methoxy, and the third is hydrogen, R 4 is not methyl; and its non-toxic, pharmaceutically acceptable acid addition salts.
Claim 3
Dependent Claim
32 words
A compound according to claim 1 wherein each of R 1 , R 2 and R 31 which can be the same or different, is hydrogen, chloro, methyl, ethyl, methoxy, or hydroxy.
Claim 4
Dependent Claim
15 words
A compound according to claim 1 or 2 wherein R 4 is hydrogen or methyl.
Claim 5
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-hydroxyethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 6
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-hydroxyethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 7
Dependent Claim
9 words
4-[2-(2',6'-Dichlorophenyl)-1-hydroxyethyl]-5-methyl-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 8
Dependent Claim
9 words
4-[2-(2',6'-Dichlorophenyl)-1-hydroxyethyl]-5-methyl-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 9
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-hydroxyethyl]-5-methyl-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 10
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-hydroxyethyl]-5-methyl-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 11
Dependent Claim
9 words
4-[2-(2'-Methylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 12
Dependent Claim
9 words
4-[2-(2'-Methylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 13
Dependent Claim
9 words
4-[2-(2',3'-Dimethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 14
Dependent Claim
9 words
4-[2-(2',3'-Dimethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 15
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 16
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 17
Dependent Claim
9 words
4-[3-(2',6'-Dimethylphenyl)-propyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 18
Dependent Claim
9 words
4-[3-(2',6'-Dimethylphenyl)-propyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 19
Dependent Claim
9 words
4-[4-(2',6'-Dimethylphenyl)-butyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 20
Dependent Claim
9 words
4-[4-(2',6'-Dimethylphenyl)-butyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 21
Dependent Claim
9 words
4-[2-(2',6'-Dichlorophenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 22
Dependent Claim
9 words
4-[2-(2',6'-Dichlorophenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 23
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-oxopropyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 24
Dependent Claim
9 words
4-[2-(2',6'-Dimethylphenyl)-1-oxopropyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 25
Dependent Claim
9 words
4-[2-(2',6'-Diethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 26
Dependent Claim
9 words
4-[2-(2',6'-Diethylphenyl)-ethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 27
Dependent Claim
9 words
4-[2-(2'-Chlorophenyl)-1-hydroxyethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 28
Dependent Claim
9 words
4-[2-(2'-Chlorophenyl)-1-hydroxyethyl]-imidazole and its non-toxic pharmaceutically acceptable acid addition salts.
Claim 29
Dependent Claim
66 words
A process for the preparation of a compound as claimed in claim 1 in which X is -CHOH- and/or -CO- which comprises reacting an imidazole aldehyde of the formula wherein R 4 is as defined in claim 1, with an arylalkylmagnesiumhalide of the formula wherein R 1 , R 2 and R 3 are as defined in claim 1 and Hal is a halogen atom. ,
Claim 30
Dependent Claim
46 words
A process for the preparation of a compound as claimed in claim 1 in which X is -CHOH- which comprises reducing a compound of the formula wherein R 1 , R 2 , R 3 , R 4 and n are as defined in claim 1.
Claim 31
Dependent Claim
52 words
18 A process for the preparation of a compound as claimed in claim 1 in which X is -CH 2 - which comprises hydrogenating a compound of the formula wherein R 1 , R21 R3 and R4 are as defined in claim 1 and n' is 0 or an integer from 1-3.
Claim 32
Dependent Claim
107 words
A process for the preparation of a compound as claimed in claim 1 in which X is -CH 2 - which comprises reacting formamide with a compound of the formula wherein R 1 , R 2 , R 3 and n are as defined in claim 1 and Q is (wherein Hal is a halogen atom, R 4 is hydrogen or methyl, and R is a substituted or unsubstituted alkyl, aralkyl or aryl group), provided that: a)when Q is , the reaction with formamide is followed by treatment of the intermediate product with acid; and the reaction with formamide is followed by hydrogenation of the intermediate product.
Claim 33
Dependent Claim
69 words
A process for the preparation of a compound as claimed in claim.1 wherein X is -CH 2 -, which comprises hydrolysing a compound of the formula wherein R 1 , R 2 , R 3 , R 4 and n are as defined in claim 1 and R 6 is an alkyl radical of 1 to 7 carbon atoms or an aryl radical of 6 to 10 carbon atoms.
Claim 34
Dependent Claim
78 words
A process for the preparation of a compound as claimed in claim 1 wherein X is -CH 2 -, which comprises hydrogenating a compound of the formula or wherein R 1 , R 2 , R 3 , R 4 , and n are as defined in claim 1, R 6 is an alkyl radical of 1 to 7 carbon atoms or an aryl radical of 6 to 10 carbon atoms, and R 12 is an aryl group.
Claim 35
Dependent Claim
149 words
A process for the preparation of a compound as claimed in claim 1 wherein R 4 is hydrogen and X is -CH 2 -, which comprises reacting a starting material of the formula wherein R 8 , R 9 , R 10 and R 11 , which can be the same or different, are each hydrogen, hydroxy, halogen, amino, -0-alkyl containing 1 to 7 carbon atoms (wherein R 6 is an alkyl radical containing 1 to 7 carbon atoms or an aryl radical containing 6 to 10 carbon atoms); or wherein R 8 and R 10 can be combined to form an oxo group, or R 9 and R11 can be combined to form an oxo group, or both R 8 and R 10 and R 9 and R 11 can simultaneously form oxo groups; with a reagent capable of converting the said starting material to the corresponding imidazole.
Claim 36
Dependent Claim
66 words
A process for the preparation of a compound as claimed in claim 1 wherein R 4 is hydrogen and X is -CH 2 -, which comprises reacting a starting material of the formula: wherein the alkyl groups contain 1 to 7 carbon atoms each and R 1 , R 2 and R 3 are as defined in claim 1, with formamide to form the corresponding imidazole.
Claim 37
Dependent Claim
51 words
A process for the preparation of a compound as claimed in claim 1 wherein R 4 is hydrogen and X is -CH 2 -, which comprises reacting formamide with an oxazole of the formula: wherein R 1 , R 2 , R 3 and n are as defined in claim 1.
Claim 38
Dependent Claim
70 words
A process for the preparation of a compound as claimed in claim 1, in which X is -CH 2 -, which comprises reacting a N-trialkylsilylimidazole of the formula wherein Y is an alkyl group, with an arylalkylhalogenide of the formula wherein R 1 , R 2 , R 3 and n are as defined in claim 1 and Hal is a halogen atom, in the presence of a Lewis acid.
Claim 39
Dependent Claim
86 words
A pharmaceutical composition comprising a 4-arylalkylimidazole of the general formula: wherein each of R 1 , R 2 and R 31 which can be the same or different, is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro; R 4 is hydrogen or an alkyl radical of 1 to 7 carbon atoms; X is R 5 is hydrogen or hydroxy; and n is an integer from 1-4, or a non-toxic, pharmaceutically acceptable acid addition salt thereof, in association with a compatible pharmaceutically acceptable carrier.
Claim 40
Dependent Claim
86 words
A pharmaceutical composition comprising a 4-arylalkylimidazole of the general formula: wherein each of R 1 , R 2 and R 31 which can be the same or different, is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro; R 4 is hydrogen or an alkyl radical of 1 to 7 carbon atoms; X is R 5 is hydrogen or hydroxy; and n is an integer from 1-4, or a non-toxic, pharmaceutically acceptable acid addition salt thereof, in association with a compatible pharmaceutically acceptable carrier.
Claim 41
Dependent Claim
14 words
A composition as claimed in claim 26 in which the carrier is a solid.
Claim 42
Dependent Claim
20 words
A composition as claimed in claim 26 in the form of a tablet, capsule, suppository, sterile solution, emulsion, or powder.
Claim 43
Dependent Claim
25 words
A substituted imidazole as defined in claim 26 or a non-toxic pharmaceutically acceptable acid salt thereof for use in therapy in the treatment of hypertension.
Claim 44
Dependent Claim
16 words
A 4-substituted imidazole as claimed in claim 1 for use in therapy as an antithrombotic agent.
Claim 45
Dependent Claim
31 words
A 4-substituted imidazole as claimed in any one of claims 4 to 15 or a non-toxic pharmaceutically acceptable acid addition salt thereof for use in therapy in the treatment of hypertension.,
Claim 46
Dependent Claim
47 words
A 4-arylalkylimidazole as defined in claim 26, wherein X is R 4 is alkyl; and R 1 , R 2 , R 3 and n are as defined in claim 26 and its non-toxic, pharmaceutically acceptable acid addition salts for use in therapy as a β-blocking agent.
Claim 47
Dependent Claim
22 words
A compound of the formula wherein R 1 , R 2 , R 3 and n are as defined in claim 1.
References Cited (Backward Citations)
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