Analogs of mevalonolactone and derivatives thereof,...

C - Chemistry – Metallurgy – 07 – C

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C07C 59/56 (2006.01) A61K 31/42 (2006.01) C07C 29/14 (2006.01) C07C 31/38 (2006.01) C07C 37/62 (2006.01) C07C 43/20 (2006.01) C07C 43/225 (2006.01) C07C 45/00 (2006.01) C07C 45/51 (2006.01) C07C 45/56 (2006.01) C07C 47/24 (2006.01) C07C 47/575 (2006.01) C07C 59/64 (2006.01) C07C 69/732 (2006.01) C07D 263/12 (2006.01) C07D 309/30 (2006.01) C07F 7/18 (2006.01)

Patent

CA 1268473

ANALOGS OF MEVALONOLACTONE AND DERIVATIVES THEREOF, PROCESSES FOR THEIRPRODUCTION, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE AS PHARMACEUTICALS Abstract Compounds of formula I Image I wherein the two groups R0 together form a radical of formula Image or -(CH2)4- , wherein R2 is hydrogen, C1-4alkyl, C1-4alkoxy, (except t-butoxy), trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy, R3 is hydrogen, C1-3alkyl, C1-3alkoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy, with the provisos that not more than one of R2 and R3 is trifluoromethyl, not more than one of R2 and R3 is phenoxy, and not more that one of R2 and R3 is benzyloxy, R1 is hydrogen, C1- alkyl, fluoro, chloro or benzyloxy, R4 is hydrogen, C1-4alkyl, C1-4alkoxy, (except t-butoxy), trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy, R5 is hydrogen, C1-3alkyl, C1-3alkoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy, R5a is hydrogen, C1-2alkyl, C1-2alkoxy, fluoro or chloro, and with the provisos that not more than one of R4 and R5 is trifluoromethyl, not more than one of R4 and R5 is phenoxy and not more than one of R4 and R5 is benzyloxy, X is -(CH2)n-, Image wherein n is 0, 1, 2 or 3 and both q's are 0 or one is 0 and the other is 1 Z is Image II wherein R6 is hydrogen or C1-3alkyl, with the general proviso that -X-7 and the R4 bearing phenyl group are ortho to each other; in free acid form or in the form of a physiologically-hydrolysable and -acceptable ester or a .delta. lactone thereof or in salt form. The compounds possess pharmacological properties and are indicated for use as pharma- ceuticals e.g. in inhibiting cholesterol biosynthesis or treating atherosclerosis.

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