# US 5,350,752 A · Dihydropyrimidine derivatives

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- Number: US 5,350,752 A
- Document ID: US5350752A
- Status: Granted
- Kind: A
- Application number: 07/812,235
- Filed: 1991-12-16
- Granted: 1994-09-27
- Earliest claimed: 1991-12-16
- Assignees: E. R. Squibb & Sons, Inc.
- Inventors: Michael A. Poss; John Lloyd; Karnail S. Atwal
- Web page: https://patentgrep.com/patent/US5350752A

## CPC

- C07D 403/10: linked by a carbon chain containing aromatic rings
- A61P 9/12: Antihypertensives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 239/74: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
- C07D 239/90: with acyclic radicals attached in position 2 or 3
- C07D 239/91: with aryl or aralkyl radicals attached in position 2 or 3
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Novel A-II receptor antagonists have the formula ##STR1## or its isomer ##STR2## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6, are as defined herein. These compounds inhibit the action of angiotensin II and are useful, therefore, for example, as antihypertensive agents.

## Claims

### Claim 1

A compound of the formula I ##STR32## or its isomer ##STR33## or a pharmaceutically acceptable salt thereof wherein R.sub.1 is alkyl, alkenyl or alkynyl or an alkyl, alkenyl or alkynyl group substituted with F or --CO.sub.2 R.sub.7 ; cycloalkyl; (cycloalkyl)alkyl of 4 to 10 carbon atoms; (cycloalkyl)alkenyl or (cycloalkyl)alkynyl of 5 to 10 carbon atoms; --NR.sub.10 R.sub.11 ; --(CH.sub.2).sub.m Z(CH.sub.2).sub.m R.sub.13 ; benzyl or benzyl substituted with 1 or 2 halogens, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, haloalkyl or nitro; --SR.sub.14 ; or --OR.sub.14 ;
R.sub.2 and R.sub.3 taken together with the carbon atoms to which they are attached form an aryl group;
R.sub.4 and R.sub.5 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo, (heterocyclo)alkyl, haloalkyl or --CO.sub.2 R.sub.7 ;
or R.sub.4 and R.sub.5 taken together with the carbon atom to which they are attached form a 5- to 7-membered carbocyclic ring which may have another 5- to 7-membered ring fused thereoto;
or R.sub.4 and R.sub.5 taken together with the carbon atom to which they are attached form a carbonyl or a thiocarbonyl group;
R.sub.6 is an acid moiety such as hydrogen, ##STR34## R.sub.7 is hydrogen, alkyl, perfluoroalkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl, benzyl ##STR35## R.sub.8 is hydrogen, alkyl, aryl, arylalkyl or cycloalkyl; R.sub.9 is alkyl, aryl, alkylaryl, arylalkyl or cycloalkyl;
R.sub.10 and R.sub.11 are independently hydrogen, alkyl of 1 to 6 carbon atoms, benzyl, .alpha.-methylbenzyl, or taken together with the nitrogen atom to which they are attached form a ring of the formula ##STR36## R.sub.12 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl or benzyl;
R.sub.13 is hydrogen; alkyl of 1 to 6 carbon atoms; cycloalkyl; alkenyl or alkynyl of 2 to 4 carbon atoms; or the above alkyl, cycloalkyl, alkenyl or alkynyl groups optionally substituted with F or --CO.sub.2 R.sub.7 ;
R.sub.14 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo, (heterocyclo)alkyl or haloalkyl;
R.sub.18 is hydrogen, alkyl of 1 to 5 carbon atoms or phenyl;
R.sub.19 is --CN, --NO.sub.2 or --CO.sub.2 R.sub.7 ;
Q is --CH.sub.2, --O--, or --NR.sub.8 ;
Z is --O--, --S-- or --NR.sub.12 ;
m is an integer of 1 to 5; and
p is 0, or the integer 1 or 2.

### Claim 2 (depends on 1)

A compound of claim 1 wherein
R.sub.1 is n-butyl;
R.sub.2 and R.sub.3 taken together with the carbon atoms to which they are attached from a fused benzene ring;
R.sub.4 and R.sub.5 together with the carbon atom to which they are attached form a carbonyl group; and
R.sub.6 is ortho tetrazolyl.

### Claim 3 (depends on 1)

A compound of claim 1 having the name 2-Butyl-3-[[5-[2-(2H-tetrazol-5-yl)phenyl]-1-naphthalenyl]methyl]-4(3H)-qu inazolinone, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 5 (depends on 4)

A method for treating hypertension comprising administering to a mammalian specie in need thereof a therapeutically effective amount of a composition of claim 4.

### Claim 6 (depends on 4)

A method for treating congestive heart failure comprising administering to a mammalian specie in need thereof a therapeutically effective amount of a composition of claim 4.

### Claim 7 (depends on 4)

A method for preventing cardiac hypertrophy comprising administering to a mammalian specie in need thereof a therapeutically effective amount of a composition of claim 4.