Pyrrolyl intermediates in the synthesis of pyrrole analogs of mevalonolactone and derivatives thereof

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United States of America Patent

PATENT NO 4973704
SERIAL NO

07338909

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Abstract

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Compounds of the formula ##STR1## wherein R.sub.1 is C.sub.1-6 alkyl not containing an asymmetric carbon atom, C.sub.3-7 cycloalkyl or ##STR2## wherein R.sub.5, R.sub.6 and R.sub.7 are as defined below, R.sub.2 is C.sub.1-6 alkyl not containing an asymmetric carbon atom, C.sub.3-7 cycloalkyl or ##STR3## wherein R.sub.8, R.sub.9 and R.sub.10 are as defined below, R.sub.3 is hydrogen, C.sub.1-6 alkyl not containing an asymmetric carbon atom, C.sub.3-7 cycloalkyl or ##STR4## wherein R.sub.11, R.sub.12 and R.sub.13 are as defined below, R.sub.4 is hydrogen, C.sub.1-6 alkyl not containing an asymmetric carbon atom, C.sub.3-7 cycloalkyl or ##STR5## wherein R.sub.14, R.sub.15 and R.sub.16 are as defined below, X is --(CH.sub.2).sub.m --, --CH.dbd.CH--, --CH.dbd.CH--CH.sub.2 --or --CH.sub.2 --CH.dbd.CH--, wherein m is 0, 1, 2 or 3, and Z is ##STR6## wherein R.sub.17 is hydrogen or C.sub.1-3 alkyl, and R.sub.18 is hydrogen, R.sub.19 or M, wherein R.sub.19 is a physiologically acceptable ester group, and M is a pharmaceutically acceptable cation, wherein each of R.sub.5, R.sub.8, R.sub.11 and R.sub.14 is independently hydrogen, C.sub.1-3 alkyl, n-butyl, i-butyl, t-butyl, C.sub.1-3 alkoxy, n-butoxy, i-butoxy, trifluoromethyl, fluoro, chloro, bromo, phenyl, phenoxy or benzyloxy, each of R.sub.6, R.sub.9, R.sub.12 and R.sub.15 is independently hydrogen, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, trifluoromethyl, fluoro, chloro, bromo, phenoxy or benzyloxy, and each of R.sub.7, R.sub.10, R.sub.13 and R.sub.16 is independently hydrogen, C.sub.1-2 alkyl, C.sub.1-2 alkoxy, fluoro or chloro, with the provisos that not more than one substituent on each of Rings A, B, C and D independently is trifluoromethyl, not more than one substituent on each of Rings A, B, C and D independently is phenoxy, and not more than one substituent on each of Rings A, B, C and D independently is benzyloxy, with the provisos that (i) the -X-Z group is in the 2- or 3-position of the pyrrole ring, (ii) the -X-Z group is ortho to both R.sub.1 and R.sub.2 and (iii) R.sub.3 is ortho to R.sub.2, 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.

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Patent Owner(s)

Patent OwnerAddress
SANDOZ PHARM CORPE HANOVER NJ

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Inventor(s)

Inventor Name Address # of filed Patents Total Citations
Wareing, James R Randolph, NJ 13 250

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