Substituted-5-methylidene hydantoins with AT.sub.1 receptor antagonist properties
AssigneeWarner-Lambert Company
InventorsJohn C. Hodges, Sylvester Klutchko
Life of this patent
Estimating the term…
Abstract
Substituted 1-benzylimidazole-5-methylidene hydantoins are disclosed as well as methods of preparing them, pharmaceutical compositions containing them, and method of using them. Intermediates useful in the preparation of the compounds of the invention are also disclosed and synthetic methods for preparing the novel intermediates. The compounds are useful as antagonists of angiotensin II and thus are useful in the control of hypertension, hyperaldosteronism, congestive heart failure, surgically induced vascular smooth muscle proliferation, and glaucoma.
Claims6
A compound of formula ##STR18## or a pharmaceutically salt thereof wherein:
- R.sub.1 is
- hydrogen,
- straight or branched alkyl or alkenyl from 1 to 8 carbon atoms;
- alkyl as above substituted with HO, NO.sub.2, CN, NH.sub.2, CO.sub.2 CH.sub.3, CO.sub.2 C.sub.2 H.sub.5, or CONH.sub.2 ;
- (CH.sub.2).sub.n aryl wherein n is an integer from 0 to 4 and aryl is Ph or Ph substituted with Cl, Br, I, F, CH.sub.3, OCH.sub.3, OH, NO.sub.2, CF.sub.3, CN, CONH.sub.2, CO.sub.2 H, NH.sub.2, NHCH.sub.3, or N(CH.sub.3).sub.2 groups, methylenedioxy;
- (CH.sub.2).sub.n heteroaryl wherein n is an integer from 0 to 3 and heteroaryl is 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, 2-oxazolyl, 2-imidazolyl, 4-thiazolyl, 4-oxazolyl, 4-imidazolyl, 5-thiazolyl, 5-oxazolyl, 5-tetrazole, 3-isoxazole, 4-isoxazole, or 5-isoxazole;
- (CH.sub.2).sub.n heteroaryl as above substituted with Me, Et, Pr, Butyl, Cl, Br, I, F, OMe, OH, NO.sub.2, NH.sub.2, NHMe, NMe.sub.2, CO.sub.2 R, CO.sub.2 H, SO.sub.2 NHR, SO.sub.3 H, CONR.sub.2, CN, CF.sub.3.
- (CH.sub.2).sub.m X(CH.sub.2).sub.n H wherein X is O, S, or N and m and n are each independently integral from 1 to 6 carbon atoms;
- (CH.sub.2).sub.n cycloalkyl wherein n is an integer from 0 to 3 and cycloalkyl is a saturated or unsaturated ring of 3 to 7 carbon atoms;
- R.sub.2 is
- cycloalkyl of from 3 to 6 carbon atoms;
- alkyl of from 1 to 6 carbon atoms,
- alkenyl of from 2 to 6 carbon atoms, OC.sub.1 -C.sub.5 alkyl, and SC.sub.1 -C.sub.5 alkyl;
- R.sub.3 is
- (CH.sub.2).sub.n CO.sub.2 Y or ##STR19## wherein Y is hydrogen or lower alkyl, n is an integer of from 0 to 3, and m is an integer of from 2 to 7;
- wherein R=C.sub.1 -C.sub.8 alkyl,
- CH.sub.2 SO.sub.2 NHCOR,
- NHSO.sub.2 NHCOR,
- NHCONHSO.sub.2 R,
- PO (OR).sub.2,
- CONHSO.sub.2 R,
- SO.sub.3 H,
- B(OH).sub.2,
- SO.sub.2 NHCOR, ##STR20## SO.sub.2 NHCONHR, NHSO.sub.2 CF.sub.3, ##STR21## R.sub.4 =R.sub.1 R.sub.5 is hydrogen or alkyl of from 1 to 4 carbon atoms;
- R.sub.6 is hydrogen, chlorine, bromine, fluorine, methyl, trifluoromethyl, or methoxy;
- and
- R.sub.7 is oxygen or sulfur.
Dependencies are inferred from the claim text.