Claims
- 1. A substituted benzimidazolyl derivative of the formula ##STR10## wherein A denotes a 1,4-butadienylene group substituted by the groups R.sub.1 and R.sub.2 and wherein additionally an unsubstituted methine group may be replaced by a nitrogen atom, wherein
- R.sub.1 denotes a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl group or a C.sub.1-3 -alkyl group and
- R.sub.2 denotes a hydrogen atom, a C.sub.1-3 -alkyl group,
- a carboxy group, an alkoxycarbonyl group having a total of 2 to 6 carbon atoms,
- a C.sub.2-5 -alkoxy group which is substituted in the 2-, 3-, 4- or 5-position by an imidazolyl, benzimidazolyl or tetrahydrobenzimidazolyl group,
- an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or a benzenesulphonylamino group, both of which may be substituted at the nitrogen atom by a C.sub.1-3 -alkyl group,
- a phthalimino or homophthalimino group, in which a carbonyl group in a phthalimino group may be replaced by a methylene group,
- a 5-, 6- or 7-membered alkyleneimino group in which a methylene group may be replaced by a carbonyl or sulphonyl group,
- a glutaric acid imino group in which the n-propylene group may be substituted by one or two C.sub.1-3 -alkyl groups or by a tetramethylene or pentamethylene group,
- a maleic acid imido group optionally mono- or disubstituted by a C.sub.1-3 -alkyl group or by a phenyl group, in which the substituents may be identical or different,
- a benzimidazol-2-yl group optionally substituted in the 1-position by a C.sub.1-6 -alkyl group or a C.sub.3-7 -cycloalkyl group, wherein the phenyl nucleus in a benzimidazol-2-yl group mentioned above may additionally be substituted by a fluorine atom or by a methyl or trifluoromethyl group,
- an imidazo[2,1-b]thiazol-6-yl, imidazo[1,2-a]pyridin-2-yl, 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyrimidin-2-yl, imidazo[4,5-b]pyridin-2-yl, imidazo[4,5-c]pyridin-2-yl, imidazo[1,2-c]pyrimidin -2-yl, imidazo[1,2-a]pyrazin-2-yl, imidazo[1,2-b]-pyridazin-2-yl, imidazo[4,5-c]pyridin-2-yl, purin-8-yl, imidazo[4,5-b]pyrazin-2-yl, imidazo[4,5-c]pyridazin-2-yl or imidazo[4,5-d]pyridazin-2-yl group,
- a pyrrolidine, piperidine or pyridine ring bound via a carbon atom, wherein a phenyl group may be fused onto the pyridine ring via two adjacent carbon atoms and a methylene group adjacent to the N-atom in a pyrrolidine or piperidine ring may be replaced by a carbonyl or sulphonyl group,
- an imidazol-4-yl group optionally substituted in the 2-position by a C.sub.1-6 -alkyl group or by a phenyl group, and substituted in the 1-position by a C.sub.1-7 -alkyl group (which may be substituted in the 2-, 3-, 4-, 5-, 6- or 7-position by a carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl or 1-oxidothiomorpholinocarbonyl group), by a C.sub.2-4 -alkyl group (substituted in the 2-, 3- or 4-position by a hydroxy, alkoxy or imidazol-1-yl group), by an alkyl group (substituted by a trifluoromethyl group, by a C.sub.3-7 -cycloalkyl group or by a phenyl group optionally mono- or disubstituted by fluorine or chlorine atoms or by trifluoromethyl, methyl or methoxy groups), by an alkyl group substituted by two phenyl groups, or by a C.sub.3-7 -cycloalkyl group, whilst unless otherwise specified the above-mentioned alkyl and alkoxy moieties may each contain 1 to 3 carbon atoms,
- a carboxy, aminocarbonyl, alkylaminocarbonyl or dialkylamino group in which each alkyl moiety may contain 1 to 6 carbon atoms, or a group which is metabolically converted in vivo into a carboxy group, or
- an R.sub.5 -NR.sub.4 -CO-NR.sub.3 - group wherein
- R.sub.3 denotes a hydrogen atom, a C.sub.1-5 -alkyl group, a cyclohexyl or benzyl group,
- R.sub.4 denotes a hydrogen atom, a C.sub.1-6 -alkyl group, an allyl, cyclohexyl, benzyl or phenyl group,
- R.sub.5 denotes a hydrogen atom or a C.sub.1-3 -alkyl group or
- R.sub.4 and R.sub.5 together with the nitrogen atom between them denote an unbranched C.sub.4-6 -cycloalkyleneimino group or a morpholino group or
- R.sub.3 and R.sub.4 together denote a C.sub.2-3 -alkylene group,
- R.sub.a denotes a C.sub.1-5 -alkyl group, a C.sub.3-5 -cycloalkyl group, an alkoxy, alkylthio or alkylamino group each having 1 to 3 carbon atoms in each alkyl moiety,
- R.sub.b denotes a carboxy, cyano, hydroxysulphonyl, 1H-tetrazolyl, 1-triphenylmethyl-tetrazolyl or 2-triphenylmethyl-tetrazolyl group, a group which is metabolically converted in vivo into a carboxy group, an alkanecarbonylaminosulphonyl, benzoylaminosulphonyl, alkanesulphonylaminocarbonyl, trifluoromethanesulphonylaminocarbonyl or phenylsulphonylaminocarbonyl group, whilst in the above-mentioned groups the alkyl and alkoxy moieties may each contain 1 to 4 carbon atoms, and
- R.sub.c denotes an alkyl group, a C.sub.3-6 -cycloalkyl group or a phenyl group which may be mono- or disubstituted by a fluorine, chlorine or bromine atom or by a hydroxy, alkoxy or alkyl group, wherein the substituents may be identical or different and the alkyl and alkoxy moieties mentioned in the above-mentioned groups may each contain 1 to 6 carbon atoms,
- or a pharmaceutically acceptable salt thereof.
- 2. A substituted benzimidazolyl derivative of the formula I according to claim 1, wherein A, R.sub.a and R.sub.c are defined as in claim 1 and R.sub.b denotes a carboxy or 1H-tetrazolyl group or a group which is metabolically converted in vivo into a carboxy group, said group being of the formulae
- -CO-OR',
- -CO-O-(HCR")-O-CO-R'" and
- -CO-O-(HCR")-O-CO-OR'"
- wherein
- R' denotes a straight-chained or branched C.sub.1-6 -alkyl group, a C.sub.5-7 -cycloalkyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, methoxymethyl or cinnamyl group,
- R" denotes a hydrogen atom or a methyl group and
- R'" denotes a straight-chained or branched C.sub.1-6 -alkyl group, a C.sub.5-7 -cycloalkyl, phenyl, benzyl, 1 -phenylethyl, 2-phenylethyl or 3-phenylpropyl group,
- or a pharmaceutically acceptable salt thereof.
- 3. A substituted benzimidazolyl derivative of the formula I according to claim 1, wherein
- A denotes a 1,4-butadienylene group substituted by the groups R.sub.1 and R.sub.2 and wherein additionally the methine group in position 7 of the benzimidazole thus formed may be replaced by a nitrogen atom, wherein
- R.sub.1 denotes a hydrogen atom or in the 4-position a fluorine, chlorine or bromine atom, a trifluoromethyl group or a C.sub.1-3 -alkyl group and
- R.sub.2 denotes a hydrogen atom,
- a C.sub.1-3 -alkyl group,
- in the 6-position an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or a benzenesulphonylamino group, both of which may be substituted at the nitrogen atom by a C.sub.1-3 -alkyl group,
- in the 6-position a phthalimino or homophthalimino group, in which a carbonyl group in a phthalimino group may be replaced by a methylene group,
- in the 6-position a 5-, 6- or 7-membered alkyleneimino group in which a methylene group is replaced by a carbonyl or sulphonyl group,
- in the 6-position a maleic acid imido group optionally mono- or disubstituted by a C.sub.1-3 -alkyl group or by a phenyl group, wherein the substituents may be identical or different,
- in the 6-position a benzimidazol-2-yl group optionally substituted in the 1-position by a C.sub.1-6 -alkyl group or by a C.sub.3-7 -cycloalkyl group, wherein the phenyl nucleus in a benzimidazol-2-yl group as mentioned above may additionally be substituted by a fluorine atom or by a methyl or trifluoromethyl group,
- an imidazo[2,1-b]thiazol-6-yl, imidazo[1,2-a]pyridin-2-yl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl, imidazo-[1,2-a]pyrimidin-2-yl or imidazo[4,5-b]pyridine2-yl group,
- in the 6-position an imidazol-4-yl group which may be substituted in the 1-position by a C.sub.1-7 -alkyl group (which may be substituted in the 2-, 3-, 4-, 5-, 6- or 7-position by a carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl or 1-oxido-thiomorpholinocarbonyl group), by a C.sub.2-4 -alkyl group (substituted in the 2-, 3- or 4-position by a hydroxy, alkoxy or imidazol-1-yl group), by an alkyl group (which is substituted by a trifluoromethyl group, by a C.sub.3-7 -cycloalkyl group or by a phenyl group optionally mono- or disubstituted by fluorine or chlorine atoms or by trifluoromethyl, methyl or methoxy groups), by an alkyl group substituted by two phenyl groups, or by a C.sub.3-7 -cycloalkyl group, whilst unless otherwise specified the above-mentioned alkyl and alkoxy moleties may each contain 1 to 3 carbon atoms,
- in the 7-position a carboxy, aminocarbonyl, alkylaminocarbonyl or dialkylamino group wherein each alkyl moiety may contain 1 to 6 carbon atoms, or a group which is metabolically converted in vivo into a carboxy group, or
- in the 6-position an R.sub.5 -NR.sub.4 -CO-NR.sub.3 - group wherein
- R.sub.3 denotes a hydrogen atom, a C.sub.1-5 -alkyl group, a cyclohexyl or benzyl group,
- R.sub.4 denotes a hydrogen atom, a C.sub.1-6 -alkyl group, an allyl, cyclohexyl, benzyl or phenyl group,
- R.sub.5 denotes a hydrogen atom or a C.sub.1-3 -alkyl group or
- R.sub.4 and R.sub.5 together with the nitrogen atom between them denote an unbranched C.sub.4-6 -cycloalkyleneimino group or a morpholino group or
- R.sub.3 and R.sub.4 together denote a C.sub.2-3 -alkylene group,
- R.sub.a denotes a C.sub.2-4 -alkyl group, a C.sub.3-4 -cycloalkyl group or a C.sub.2-3 -alkoxy group,
- R.sub.b denotes a carboxy or 1 H-tetrazolyl group or a group which is metabolically converted in vivo into a carboxy group, said group being of the formulae
- -CO-OR',
- -CO-O-(HCR")-O-CO-R'" and
- -CO-O-(HCR")-O-CO-OR'"
- wherein
- R' denotes a straight-chained or branched C.sub.1-6 -alkyl group, a C.sub.5-7 -cycloalkyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, methoxymethyl or cinnamyl group,
- R" denotes a hydrogen atom or a methyl group and
- R'" denotes a straight-chained or branched C.sub.1-6 -alkyl group, a C.sub.5-7 -cycloalkyl, phenyl, benzyl, 1-phenylethyl, 2-phenylethyl or 3-phenylpropyl group, and
- R.sub.c denotes a C.sub.1-3 -alkyl group, a C.sub.1-6 -cycloalkyl group or a phenyl group,
- or a pharmaceutically acceptable salt thereof.
- 4. A substituted benzimidazolyl derivative of the formula I according to claim 1, wherein
- A denotes a 1,4-butadienylene group in which the methine group in positions 4 and 6 of the benzimidazole thus formed are substituted by methyl groups and the methine group in position 7 is replaced by a nitrogen atom, or
- A denotes a 1,4-butadienylene group which is substituted by the groups R.sub.1 and R.sub.2, wherein
- R.sub.1 denotes a hydrogen atom or in the 4-position a methyl group and
- R.sub.2 in the 6-position denotes a 1-methyl-benzimidazol-2-yl group,
- R.sub.a denotes a C.sub.2-4 -n-alkyl group,
- R.sub.b denotes a carboxy or 1H-tetrazolyl group and
- R.sub.c denotes a C.sub.1-3 -alkyl group, a C.sub.3-6 -cycloalkyl group or a phenyl group,
- or a pharmaceutically acceptable salt thereof.
- 5. A compound selected from the group consisting of:
- 1-hydroxycarbonylmethyl-2-phenyl-5[(2-ethyl-5,7-dimethylimidazo[4,5b]pyridin-3-yl)-methyl]-benzimidazole,
- 1-hydroxycarbonylmethyl-2-phenyl-6-[(2-n-propyl-4-methyl-6-(1-methyl -benzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-benzimidazole and
- 1-[(1H-tetrazol-5-yl )-methyl]-2-phenyl-5-[(2-n-propyl-4-methyl-6-(1-methylbenzimidazol -2-yl)-benzimidazol-1-yl )-methyl]-benzimidazole,
- and the pharmaceutically acceptable salts thereof.
- 6. A pharmaceutical composition, suitable for the treatment of hypertension or cardiac insufficiency, containing a thereapeutic amount of a compound according to claim 1, 2, 3, 4, or 5 and a pharmaceutically acceptable diluent.
- 7. A method for treating hypertension in a mammal which comprises administering to a mammal suffering from hypertension a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
- 8. A method for treating cardiac insufficiency in a mammal which comprises administering to a mammal suffering from cardiac insufficiency a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
- 9. A method for treating an ischaemic peripheral circulatory disorder in a mammal which comprises administering to a mammal suffering from the same a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
- 10. A method for treating myocardial ischaemia in a mammal which comprises administering to a mammal suffering from the same a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
- 11. A method for treating diabetic nephropathy in a mammal which comprises administering to a mammal suffering from the same a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
- 12. A method for treating glaucoma in a mammal which comprises administering to a mammal suffering from the same a therapeutic amount of a compound according to claims 1, 2, 3, 4, or 5.
Priority Claims (1)
Number |
Date |
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42 07 904.7 |
Mar 1992 |
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Parent Case Info
This is a continuation of application Ser. No. 08/025,303, filed Mar. 2, 1993, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5190942 |
Poss |
Mar 1993 |
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Foreign Referenced Citations (2)
Number |
Date |
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0468470 |
Jan 1992 |
DEX |
0502314 |
Sep 1992 |
DEX |
Continuations (1)
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25303 |
Mar 1993 |
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