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US 5,290,801 AGranted
Benzimidazoles for the treatment of atherosclerosis
AssigneeThe Du Pont Merck Pharmaceutical Company
InventorsC. Anne Higley, Thomas P. Muduskuie, Jr., Ruth R. Wexler, Richard G. Wilde
Life of this patent
Estimating the term…
Abstract
This invention relates to imidazoles, namely, fused-ring heterocycles as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT), pharmaceutical compositions containing them, processes for their preparation, and their use as antihypercholesterolemic and/or antiatherosclerotic agents for the treatment of atherosclerosis.
Claims8
A method of treating hypercholesterolemia or atherosclerosis in a mammal in need of such treatement comprising administering to the mammal a therapeutically effective amount of a compound of the formula (I):
- ##STR51## wherein W is:
- ##STR52## A, B, D, and E are each CR.sup.1 ;
- Q is NH, NCH.sub.3 ;
- X is S(O).sub.r, O, NR.sup.5 or CH.sub.2 ;
- J is C.sub.2 -C.sub.10 alkyl, C.sub.3 -C.sub.10 branched alkyl, C.sub.3 -C.sub.10 alkenyl or C.sub.3 -C.sub.10 alkynyl;
- Y is O, S, or NH;
- Z is NHR.sup.4, OR.sup.4 or R.sup.4 ;
- R.sup.3 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.8 alkenyl or alkynyl, C.sub.7 -C.sub.14 aralkyl where the aryl group is optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, OH, CN, CO.sub.2 H, CF.sub.3, Carbo(C.sub.1-4)alkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, BR, Cl, OH, CN, CO.sub.2 H, CF.sub.3, Carbo(C.sub.1 -C.sub.4)alkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, OH, CN, CO.sub.2 H, CF.sub.3, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- 2-, 3-, or 4-pyridinyl, pyrimidinyl;
- or biphenyl;
- R.sup.4 is C.sub.1 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.3 -C.sub.6 alkenyl or alkynyl, C.sub.1 -C.sub.3 perfluoroalkyl,
- C.sub.7 -C.sub.14 aralkyl where the aryl group is optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, C.sub.3 -C.sub.8 branched alkyl, F, Br, Cl, OH, CN, CO.sub.2 H, CF.sub.3, Carbo(C.sub.1 -C.sub.4)alkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, C.sub.3 -C.sub.8 branched alkyl, F, Br, Cl, OH, CN, CO.sub.2 H, CF.sub.3, Carbo(C.sub.1 -C.sub.4)alkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, C.sub.3 -C.sub.8 branched alkyl, F, Br, Cl, OH, CN, CO.sub.2 H, CF.sub.3, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.6 R.sup.7 or NR.sup.6 COR.sup.7 ;
- 2-, 3-, or 4-pyridinyl, pyrimidinyl;
- or biphenyl;
- R.sup.5 is H, C.sub.1 -C.sub.6 alkyl or benzyl;
- R.sup.6 and R.sup.7 are selected independently from H or C.sub.1 -C.sub.4 alkyl;
- r is 0 or 2;
- or a pharmaceutically acceptable salt thereof.
19 more elements
Dependencies are inferred from the claim text.