Sandoz Pharm. Corp.

Sandoz Gmbh

Sandoz Pharmaceuticals Corp.

James R Wareing

Charles F Jewell, Jr

Robert E Damon, Ii

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

Pyrrolyl intermediates in the synthesis of pyrrole analogs of

Compounds of the formula ##STR1## in which Y is ##STR2## X is O or S; Z is --CHOH--CH.sub.2 --CHOH--CH.sub.2 --COOH, an ester or salt thereof or the lactone thereof; and

Analogs of mevalonolactone and derivatives thereof

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.7-7 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

Pyrrole analogs of mevalonolactone, derivatives thereof and

Compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein the various substituents are defined hereinbelow and 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.

Imidazole analogs of mevalonolactone and derivatives thereof for use in

Compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein the various substituents are defined herein below, 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.

Imidazolyl-3,5-di-(diphenyl-butylsilyloxy) carboxylic acid ester

7-Substituted lower alkyl hept-6-enoates and 4-hydroxytetrahydropyran-2-ones bearing 6-olefinic substituents (e.g.,) ethyl erythro-3,5-dihydroxy-7-phenyl-hept-6-enoates are prepared by a multi-step process. The process involves 3-protected-lower alkyl 3,5-dihydroxy-hept-6-enoates, which are obtained by cleaving corresponding 6.alpha.-vinyl-4.beta.-protected hydroxy-tetrahydro 2H-pyran-2-ones. The final products are useful as anti hypercholesteremic agents.

Preparation of lactones

Compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein the various substituents are defined hereinbelow, 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.

Intermediate imidazole acrolein analogs

7-Substituted lower alkyl hept-6-enoates and 4-hydroxy-tetrahydropyran-2-ones bearing 6-olefinic substituents (E), (Z), ethyl erythro-3,5-dihydroxy-7-phenyl-hept-6-enates are prepared by a multi-step process involving lower alkyl 3,5-dihydroxy-hept-6-enates. The final products are useful as anti hypercholesteremic agents.

Preparation of olefinic compounds and intermediates thereof

6-trans-indol-2-yl-ethenyl)-4-hydroxy-tetrahydro-2H-pyran-2-ones of formula I are obtained by a multi-step reaction involving the procedure: ##STR1## wherein p.sup.1 is trisubstituted silyl protective group, and Z is a 2-indolyl radical which may be bear at the 4, 5, 6 and 7-positions up to two substituents such as alkyl, alkoxy, halo and CF.sub.3, and at either one the 1 or 3-positions a substituted or unsubstituted phenyl; and at the other an assymetric alkyl, cycloalkyl or aralkyl radical. Compounds I, e.g. (E)-trans-6-[1'-methyl-3'-(4'-fluorophenyl)indol-2'-ylethenyl]3,4,5,6 -tetrahydro-4-hydroxy-2H-pyran-2-one(4R,6S); are useful as anti-atheroselerotic agents.

4-trisubstituted silyl protected

Compounds of the formula ##STR1## wherein R.sub.1 is C.sub.1-6 alkyl not containing an asymmetric carbon atom,

Cholesterol biosynthesis inhibiting pyrazole analogs of mevalonolactone

Single enanitiomers of 6-(2-hydrocarbyl-substituted ethenyl)-bearing, 4-hydroxy tetrahydro-2H-pyran-2-ones, e.g., 6.alpha.-[2-(2-methyl-1-naphthyl)ethenyl]-3,4,5,6-tetrahydro-4.beta.-hydro xy-2H-pyran-2-one (4R,6S) are obtained by a multi-step process which includes protecting and deprotecting hydroxy groups at various stages.

(Tetrahydropyran-2-yl)-aldehydes

The compounds are 1-(3-halo-1,2-dioxopropyl)-cycloamines, eg 1-(3-chloro-1,2-dioxopropyl)-piperidine, and are useful as fungicides and bactericides. They can be prepared by halogenation of a corresponding 1-(1,2-dioxopropyl)-cycloamine.

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Randolph, NJ, United States of America

James R Wareing