Cholesterol biosynthesis inhibiting pyrazole analogs of mevalonolactone and its derivatives

Abstract

Abstract Compounds of the formula ##STR1## wherein R 1 is C 1-6 alkyl not containing an asymmetric carbon atom, each of R 2 and R 5 is independently hydrogen, C 1-3 alkyl, n-butyl, i-butyl, t-butyl, C 1-3 alkoxy, n-butoxy, i-butoxy, trifluoromethyl, fluoro, chloro, phenyl, phenoxy or benzyloxy, each of R 3 and R 6 is independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy, each of R 4 and R 7 is independently hydrogen, C 1-2 alkyl, C 1-2 alkoxy, fluoro or chloro, with the provisos that not more than one of R 2 and R 3 is trifluoromethyl, not more than one of R 2 and R 3 is phenoxy, not more than one of R 2 and R 3 is benzyloxy, not more than one of R 5 and R 6 is trifluoromethyl, not more than one of R 5 and R 6 is phenoxy, and not more than one of R 5 and R 6 is benzyloxy, X is --(CH 2 ) m --, --CH═CH--, --CH═CH--CH 2 -- or --CH 2 --CH═CH--, wherein m is 0, 1, 2 or 3, and Z is ##STR2## wherein R 10 is hydrogen or C 1-3 alkyl, wherein R 12 is a physiologically acceptable and hydrolyzable ester group, and M is a pharmaceutically acceptable cation, with the provisos that (i) the--X--Z group is in the 4- or 5-position of the pyrazole ring, and (ii) the R 1 group and the --X--Z group are ortho to each other, the use thereof for inhibiting cholesterol biosynthesis and lowering the blood cholesterol level and, therefore, in the treatment of hyperlipoproteinemia and atherosclerosis, pharmaceutical compositions comprising such compounds and processes for and intermediates in the synthesis of such compounds.

Inventors

• 👤 James R. Wareing

Bibliographic Details