Pfizer Corporation

Frederick J Walker

Peter A McCarthy

Ernest S Hamanaka

John L LaMattina

George Chang

Lawrence S Melvin, Jr

Brian Thomas O'Neill

Thien V Truong

Thien Truong

Compounds of the formula ##STR1## the pharmaceutically acceptable salts thereof, wherein Q and R.sup.1 are as defined below, and novel carboxylic acid and acid halide intermediates used in the synthesis of such compounds. The compounds of formula I are inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) and are useful as hypolipidemic and antiatherosclerosis agents.

N-aryl and N-heteroarylamide and urea derivatives as inhibitors of acyl

Compounds of the formula ##STR1## wherein R.sup.21 and R.sup.22 are as defined in the specification which are intermediates useful in the preparation of compounds of the formula ##STR2## and the pharmaceutically acceptable salts thereof, wherein Q and R.sup.1 are as defined in the specification. The compounds of formula I are inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) and are useful as hypolipidemic and antiatherosclerosis agents.

Intermediates for making N-aryl and N-heteroarylamide and urea

Variously substituted 3,5-dihydroxy-6,8-nonadienoic acids and esters, are blood cholesterol lowering agents and so are useful in the prevention and treatment of cardiovascular diseases such as atherosclerosis.

3,5-dihydroxy-6,8-nonadienoic acids and derivatives as

This invention relates to the use of certain derivatives of 5-hydroxy and 5-methoxy 2-aminopyrimidines of the formula ##STR1## and the pharmaceutically-acceptable salts thereof, wherein R.sup.1 is H or CH.sub.3 ; R.sup.2 is (C.sub.3 -C.sub.15) straight chain alkyl or (C.sub.7 -C.sub.20)phenylalkyl which may be substituted in the phenyl by one or two fluoro or chloro substituents; and R.sup.3 is H or CH.sub.3 to inhibit interleukin-1 production in a mammal. This invention also relates to the use of such compounds for treating interleukin-1 mediated disorders and dysfunctions such as bone and connective tissue metabolism disorders and immune dysfunction in a mammal. The methods of this invention comprise administering an interleukin-1 production inhibiting amount of the compounds and salts of this invention to such a mammal.

Derivatives of 5-hydroxy and 5-methoxy 2-amino-pyrimidines as inhibitors

2-substitutedmethylamino-amino 5-(hydroxy or alkoxy) pyridines and derivatives thereof are disclosed. The compounds are inhibitors of leukotriene synthesis and are therefore useful for the treatment of pulmonary, inflammatory, dermatological, allergic and cardiovascular diseases.

Leukotriene-synthesis-inhibiting 2-substitutedmethylamino-5-(hydroxy or

2-Amino and 2-thio-4-substituted-5-(hydroxy or alkoxy)-pyrimidines, which may be 6-substituted, and derivatives thereof are disclosed. The compounds are inhibitors of leukotriene synthesis and are, therefore, useful for the treatment of pulmonary, inflammatory, dermatological, allergic and cardiovascular diseases. The compounds are also cytoprotective and therefore, useful in the treatment of peptic ulcers.

Derivatives of hydroxyprimidines as leukotriene synthesis inhibitors

A compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is hydrogen; R.sup.2 is (C.sub.1 -C.sub.15) alkyl, (C.sub.3 -C.sub.15)alkenyl, phenyl, substituted phenyl, (C.sub.7 -C.sub.20)-phenylalkyl, or substituted (C.sub.7 -C.sub.20)phenylalkyl wherein the substituents on the substituted phenyl and substituted phenylalkyl are independently one or two of fluoro, chloro, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3 alkoxy, and trifluoromethyl; or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a pyrrolodinyl, substituted pyrrolidinyl, piperidyl or substituted piperidyl group, wherein the substituents on said substituted pyrrolidinyl and piperidyl groups are independently one of (C.sub.1 -C.sub.6)alkyl, phenyl, and (C.sub.7 -C.sub.9)phenylalkyl; and R.sup.3 is hydrogen, (C.sub.1 -C.sub.6)alkyl, phenyl, substituted phenyl, (C.sub.7 -C.sub.9)phenylalkyl, or substituted (C.sub.7 -C.sub.9)phenylalkyl, wherein the substituents on the substituted phenyl and substituted phenylalkyl are independently one or two of fluoro, chloro, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, and trifluoromethyl. The compounds are useful in treating inflammation or other leukotriene mediated diseases, including plumonary, asthmatic, allergic, and gastrointestinal diseases.

2-amino-5-hydroxy-4-pyrimidones

2-Amino-4-substituted-5-(hydroxy or alkoxy)pyrimidines, which may be 6-substituted, and derivatives thereof are inhibitors of leukotriene synthesis and are therefore useful for the treatment of pulmonary, inflammatory, allergic and cardiovascular diseases. The compounds are also cytoprotective and therefore useful in the treatment of peptic ulcers.

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Preston, CT, United States of America

Frederick J Walker