2-Methyl-3,5-di:hydroxy-hept-(6E)-enoic acid derivs. and lactone(s) - with e.g. heterocyclic substits., are HMG-COA-reductase inhibitors for treatment and prophylaxis of hypercholesterolaemia

摘要

Heptenoic acid derivatives of formula RCH=CH-CHOH-CH2-CHOH-CHMe-COOR' (I) and lactones of formula (II) are new. In (I), (II), (a) and (b) R is a group of formula (a), (b) or -CHR11-CHR12R13 or -CR11=CR12R13. R1-R8, R11-R13 = R' or OH. R= linear or branched 1-6C alkyl, 2-6C alkenyl, 3-6C saturated or mono- or di-unsaturated cyclic hydrocarbyl of phenyl optionally substituted with 1-3 of 1-4C, halogen or 1-4C alkoxy. The group X=Y-Z is CR3=CR4-CR5, N=CR4-CR5, N=N-CR5 or N=CR4-N. The group U-V-W is C-NR9-CR8, C-O-CR8, C-S-CR8, C-NR9-N, C-O-N(=C-N-O), C-S-N(=C-N-S), N-CR10=CR8, N-N=CR8 or N-CR10=N. R9, R10= R'. R' = H, 1-6C alkyl, NH4 or alkali metal. (I) are prepared from aldehydes of formula RCH=CH-CHO by conversion to RCH=CH-CHOH-CH2-CO-CHMe-COOR' (R'=1-6C alkyl) and reduction of the carbonyl group. The compounds are made up into tablets, pills or capsules containing 10-500 mg (I) or (II) administered 1-4 times daily. USE/ADVANTAGE - (I) and (II) are potent inhibitors of HMG-CoA reductase with inhibition levels similar to the 2-unsubstituted derivatives. They are used for the prophylaxis and treatment of hypercholesterolaemia (claimed).