# US 5,350,751 A · Substituted imidazoles, pharmaceutical compositions containing these, and the use thereof as antagonists of angiotensin II receptors for the treatment of high blood pressure

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,350,751 A
- Document ID: US5350751A
- Status: Granted
- Kind: A
- Application number: 07/679,233
- Filed: 1991-04-02
- Granted: 1994-09-27
- Earliest claimed: 1990-04-04
- Assignees: Hoechst Aktiengesellschaft
- Inventors: Adalbert Wagner; Rainer Henning; Hermann Gerhards; Bernward Scholkens; Jean-Paul Vevert; Jean-Claude Caille
- Web page: https://patentgrep.com/patent/US5350751A

## CPC

- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 9/12: Antihypertensives
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/14: containing three or more hetero rings
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to compounds of the formula I ##STR1## in which X, Y and Z are identical or different and are N or CR.sup.2, R.sup.1 and R.sup.2 are as defined in the description, L is an alkylene radical, q is 0 or 1, and A is the radical of a fused heterobicyclic compound. The invention furthermore relates to a process for preparing the said compounds, agents containing these, and the use thereof in the treatment of high blood pressure.

## Claims

### Claim 1

A compound of the formula I ##STR43## in which Z is N;
X and Y are identical or different and are CR.sup.2 ;
R.sup.1 is (C.sub.3 -C.sub.7)-alkyl, (C.sub.3 -C.sub.7)-alkenyl or (C.sub.3 -C.sub.7)-alkynyl;
R.sup.2 is independently chlorine, bromine, --S(O).sub.r R.sup.6, --COR.sup.8, or (C.sub.1 -C.sub.6)-alkyl substituted by hydroxyl;
R.sup.3 is independently hydrogen or (C.sub.1 -C.sub.4)-alkyl;
R.sup.5 is independently hydrogen, (C.sub.1 -C.sub.6)-alkyl, (C.sub.3 -C.sub.8)-cycloalkyl, phenyl, or benzyl;
R.sup.6 is independently hydrogen, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkanoyl, or (C.sub.6 -C.sub.12)-aryl,
wherein (C.sub.6 -C.sub.12)-aryl is unsubstituted or substituted by 1 or 2 identical or different radicals selected from halogen, hydroxyl, methoxy, nitro, cyano, CO.sub.2 R.sup.3 and trifluoromethyl;
R.sup.7 is independently hydrogen, (C.sub.1 -C.sub.4)-alkyl, or (C.sub.6 -C.sub.12)-aryl-(C.sub.1 -C.sub.4)-alkyl;
R.sup.8 is independently hydrogen, (C.sub.1 -C.sub.4)-alkyl, OR.sup.5 or morpholino;
A is a fused heterobicyclic radical selected from a radical of benzothiophene, benzofuran, indole, isoindole, indazole, benzimidazole, quinoline, isoquinoline, phthalazine, quinoxaline, quinazoline, cinnoline, benzothiazole, benzothiazole-1,1-dioxide, coumarin, chroman, benzoxazole, benzisothiazole, benzodiazines, benzotriazole, benzotriazine, benzoxazine, imidazopyridine, imidazopyrimidine, imidazopyrazine, imidazopyridazine, imidazothiazole, pyrazolopyridine, thienopyridine and pyrrolopyrimidine, which is unsubstituted or substituted by up to 3 identical or different radicals R.sup.14 or --(CH.sub.2).sub.n-1 --(CHR.sup.6 --CH.sub.2).sub.o-1 --R.sup.15 ;
R.sup.14 is independently (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxy, cyano, amino, nitroso, nitro, fluorine, chlorine, bromine, hydroxyl, CH.sub.2 OR.sup.7, (C.sub.1 -C.sub.4)-alkanoyloxy, (C.sub.1 -C.sub.4)-alkanoyl, benzoyl, --NH--CO--R.sup.7 or tetrazolyl;
R.sup.15 is independently (C.sub.6 -C.sub.12)-aryl, cyano, chlorine, bromine, --CO.sub.2 R.sup.3, or (C.sub.6 -C.sub.12)-aryl which is substituted by 1 or 2 identical or different radicals selected from halogen, cyano, nitro, NR.sup.6 R.sup.7 and hydroxyl;
L is (C.sub.1 -C.sub.3)-alkanediyl;
n is independently 1 or 2;
o is independently 1 or 2;
q is 0 or 1;
r is independently 0, 1 or 2,
or a physiologically tolerated salt thereof.

### Claim 2 (depends on 1)

A compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 1, in which A is a radical selected from a radical of benzoxazole, benzothiophene, imidazopyridine, imidazopyrimidine, benzofuran, and indole, which is unsubstituted or substituted by up to 3 identical or different radicals R.sup.14 or --(CH.sub.2).sub.n-1 --(CHR.sup.6 --CH.sub.2).sub.o-1 --R.sup.15.

### Claim 3 (depends on 2)

A compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 2 in which
R.sup.2 is independently chlorine, bromine, --S(O).sub.r R.sup.6, or --COR.sup.8 ;
R.sup.14 is independently tetrazolyl;
R.sup.15 is independently --CO.sub.2 R.sup.3 ;
q is zero; and
L is CH.sub.2.

### Claim 4 (depends on 1)

A compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 1 in which
R.sup.2 is independently chlorine bromine --S(O).sub.r R.sup.6, or --COR.sup.8 ;
R.sup.14 is independently tetrazolyl;
R.sup.15 is independently --CO.sub.2 R.sup.3 ;
q is zero; and
L is CH.sub.2.

### Claim 5 (depends on 1)

A pharmaceutical composition for the treatment of high blood pressure which comprises a pharmaceutically effective amount for said treatment of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 1, together with a pharmaceutically acceptable carrier.

### Claim 6 (depends on 5)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutical composition as claimed in claim 5.

### Claim 7 (depends on 1)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutically effective amount of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 1.

### Claim 8 (depends on 4)

A pharmaceutical composition for the treatment of high blood pressure which comprises a pharmaceutically effective amount for said treatment of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 4, together with a pharmaceutically acceptable carrier.

### Claim 9 (depends on 3)

A pharmaceutical composition for the treatment of high blood pressure which comprises a pharmaceutically effective amount for said treatment of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 3, together with a pharmaceutically acceptable carrier.

### Claim 10 (depends on 2)

A pharmaceutical composition for the treatment of high blood pressure which comprises a pharmaceutically effective amount for said treatment of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 2, together with a pharmaceutically acceptable carrier.

### Claim 11 (depends on 10)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutical composition as claimed in claim 10.

### Claim 12 (depends on 9)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutical composition as claimed in claim 9.

### Claim 13 (depends on 8)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutical composition as claimed in claim 8.

### Claim 14 (depends on 4)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutically effective amount of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 4.

### Claim 15 (depends on 3)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutically effective amount of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 3.

### Claim 16 (depends on 2)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutically effective amount of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 2.

### Claim 17

A compound of the formula I ##STR44## in which R.sup.1 is --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3 ;
r is 0, 1, or 2;
R.sup.6 is (C.sub.1 -C.sub.4)-alkyl;
R.sup.8 is hydrogen or --OR.sup.5 ; and
R.sup.5 is hydrogen or (C.sub.1 -C.sub.6)-alkyl,
or a physiologically tolerated salt thereof.

### Claim 18 (depends on 17)

A pharmaceutical composition for the treatment of high blood pressure which comprises a pharmaceutically effective amount for said treatment of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 17, together with a pharmaceutically acceptable carrier.

### Claim 19 (depends on 18)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutical composition as claimed in claim 18.

### Claim 20 (depends on 17)

A method for the treatment of high blood pressure which comprises administering to a host in recognized need of said treatment a pharmaceutically effective amount of a compound of the formula I or a physiologically tolerated salt thereof as claimed in claim 17.