American Home Products Corporation

Wyeth

John Wyeth Brother, Limited

American Home Procucts Corporation

Sie-Yearl Chai

Hassan Mahmoud Elokdah

Theodore S Sulkowski

Donald P Strike

Robin G Shepherd

Maynard E Lichty

Arnold S Milowsky

John P Yardley

John Babiak

Imidazo-isoquinolin-5-one derivatives, pyrimido-isoquinolin-6-one derivatives and imidazo-naphthyridin-5-one derivatives

Styryl benzimidazole derivatives

Disclosed herein are compounds of formula I or II:

Benzimidazole derivatives

The compound of formula I: ##STR1## in which R.sup.1 is alkyl or alkenyl; R.sup.2 is alkyl and R.sup.3 and R.sup.4 are, independently, hydrogen or alkyl; or R.sup.2 is hydrogen and R.sup.3 and R.sup.4 taken together are ortho substituted trimethylene or tetramethylene are useful for increasing blood serum HDL levels.

2-thioxo-imidazolidin-4-one derivatives

The compound of formula I ##STR1## in which R.sup.1 is alkyl, alkenyl, aryl or arylalkyl; R.sup.2 is alkyl, R.sup.3 is a halogen and R.sup.4 is hydrogen; or R.sup.2 is hydrogen, R.sup.3 is a halogen, and R.sup.4 is alkyl are useful for increasing blood serum HDL levels.

This invention relates to the use of 2-thioxotetrahydropyrimidin-4-one derivatives to increase HDL cholesterol concentration and as therapeutic compositions for treating atherosclerotic conditions such as dyslipoproteinemias and coronary heart disease. The compounds of this invention are represented by the formula: ##STR1## wherein: R is C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, or C.sub.2 -C.sub.6 alkynyl; and

2-thioxo-tetrahydropyrimidin-4-one derivatives

The compound of formula I ##STR1## in which R.sup.1 is alkyl; and R is alkyl, naphthyl, benzhydryl, fluorophenylmethyl, phenethyl, 1-(fluorophenyl)ethyl, 5-chloro-2-methoxyphenyl, trifluoromethoxyphenyl, trifluoromethylphenyl, methylsulfanylphenyl or pyridyl are useful for increasing blood serum HDL levels.

The use of compounds of the formula: ##STR1## where R.sub.1 is alkyl, trifluoromethyl or pyridinyl; R.sub.2 is H, alkyl or substituted arylalkyl, in which the substituents are one or two halogens, carboxyl or alkoxycarbonyl groups; R.sub.3 and R4 are H, alkyl, halogen or nitro; or a pharmaceutically acceptable salt thereof, as inhibitors of smooth muscle cell proliferation.

Use of 2-substituted benzimidazole as smooth muscle cell proliferation

Disclosed herein are compounds of the formula: ##STR1## where Ar.sub.1 and Ar.sub.2 are, independently, pyridinyl, quinolinyl, 1,4-benzodioxanyl, dihydro-1,4-benzodioxanyl, pyrrolyl, azaindolyl or carbazolyl, or a pharmaceutically acceptable salt thereof, which are useful as inhibitors of smooth muscle cell proliferation.

Diheterocyclic styryl nitriles

Disclosed herein are compounds of the formula: ##STR1## where R.sub.1 is substituted phenyl in which the substituents are one or two halogens, alkyl groups, carboxyl groups or alkoxycarbonyl groups;

2-substituted benzimidazole derivatives

The compound of formula I ##STR1## in which R is alkynyl; and X and Y are, independently, alkyl, halo, perfluoralkyl, perfluoralkoxy, or, taken together, X and Y are ortho substituted trimethylene or tetramethylene are useful for increasing blood serum HDL levels.

Disclosed herein are compounds of the formula: ##STR1## where R.sub.1 is alkyl, trifluoromethyl or pyridinyl;

A method for increasing the HDL cholesterol concentration in the blood of a mammal in need of increased HDL cholesterol blood concentration, which comprises administering to said mammal, orally or parenterally, a compound of formula I: ##STR1## wherein R is alkyl; a substituted or unsubstituted aromatic N, O or S heterocycle; substituted or unsubstituted aryl, arylalkyl, benzhydryl or indanyl, in which the substituents are one to three members independently selected from the group consisting of alkyl, alkoxy, alkylthio, alkenyl, alkynyl, halo, perfluoroalkyl, perfluoroalkyl or hydroxy; and R.sup.1 is aryl, alkyl, alkenyl, alkynyl or substituted aryl where the substituents are one to three members independently selected from the group consisting of alkyl, alkoxy, alkylthio, alkenyl, alkynyl, halo, perfluoroalkyl, perfluoroalkoxy or hydroxy.

Use of 2-thioxo-imidazolin-4-one derivatives in the treatment of

The invention concerns a process for preparng a thiazolo[3,2-a]benzimidazole of formula I ##STR1## in which formula n is 1 or 2, and R.sub.1 is hydrogen, lower alkyl, lower alkoxy, trifluoromethyl or halo, or a salt thereof which comprises dehydrating a compound of formula II, ##STR2## or a salt thereof wherein n and R, are a defined above, and COOR is an acid or ester function in the presence of an acid selected from sulphuric, sulphonic and phosphoric acid or mixtures thereof and if desired or required an inert solvent provided that if water is present then the amount of water is less than about 15% by volume of the acid, the reaction being carried out with heating if necessary.

Process for preparing thiazolobenzimidazoles and intermediates used

The invention concerns a process for preparing a thiazolo[3,2-a]benzimidazole of formula I ##STR1## in which formula n is 1 or 2, and R.sub.1 is hydrogen, lower alkyl, lower alkoxy, trifluoromethyl or halo, or a salt thereof which comprises dehydrating a compound of formula II, ##STR2## or a salt thereof wherein n and R, are as defined above, and COOR is an acid or ester function in the presence of an acid selected from sulphuric, sulphonic and phosphoric acid or mixtures thereof and if desired or required an inert solvent provided that if water is present then the amount of water is less than about 15% by volume of the acid, the reaction being carried out with heating if necessary.

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Lawrenceville, NJ, United States of America

Sie-Yearl Chai