Hoffmann-la Roche Inc.

John G Mullin

Richard W Kierstead

Jefferson Wright Tilley

Keiji Nakamura

Hiroshi Watanabe

Robert W Guthrie

Hans Bruderer

Jay P O'Brien

Mitsuru Tateishi

Ronald A LeMahieu

Sidney Teitel

Joseph Triscari

David F Kachensky

Guy P Heathers

Alan J Higgins

Teitel Sidney

The invention relates to compounds of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.2 ' X, Y, Z, A, B, Q and n are as described herein. Their pharmaceutically acceptable salts, and when appropriate, enantiomers, racemates, diastereomers or mixtures thereof or geometric isomer or mixtures thereof, and pharmaceutically acceptable salts thereof. The compounds of formula I inhibit enzyme carnitine acyltransferase 1 (CAT-1) and are therefore useful in the prevention of injury to ischemic tissue, and can limit infarct size, improve cardiac function and prevent arrhythmias during and following a myocardial infarction.

Cat-1 inhibitors, pharmaceutical compositions and methods of use

The invention relates to compounds of the formula ##STR1## wherein Y and Y' are hydrogen or taken together are O or S, *A is paraphenylene or *----(CH.sub.2).sub.n --(X).sub.s --(CH.sub.2).sub.r ----, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, m is an integer from 0 to 1, s is an integer from 0 to 1, provided that when s is 1, n+m must be at least 2, t is an integer from 0 to 10, R.sub.1 and R.sub.2, independently, are lower alkyl, lower alkenyl or aryl, or one of R.sub.1 or R.sub.2 is hydrogen and the other is ##STR2## wherein W is ##STR3## --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --, O, S, or ##STR4## and X.sub.1 is lower alkyl, phenyl unsubstituted or mono-, di- or trisubstituted by lower alkoxy, lower alkyl or halogen, and X.sub.2, X.sub.3 and X.sub.4, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, R.sub.3 is hydrogen, lower alkyl or aryl, R.sub.4 is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R.sub.5 is hydrogen or lower alkyl,

Pyridine compounds which are useful in treating a disease state

Compounds of the formula ##STR1## wherein R.sub.2, R.sub.3 and R.sub.4 are independently, hydrogen or methyl; A is 3-pyridinyl which is unsubstituted, or substituted by lower alkyl, phenyl, or naphthyl, are described. The compounds of the invention are intermediates in the preparation of antiarrhythmic agents.

Antiarrhythmic agents

Compounds of the formula: ##STR1## wherein R.sub.1 is --alkylene'-13 NH.sub.2 or --alkylene'--A'; R.sub.2, R.sub.3 and R.sub.4 are independently hydrogen or methyl; A and A' are, independently, unsubstituted or lower alkyl or aryl substituted pyridinyl, imidazolyl, or pyrimidinyl; and when, an asymmetric carbon is present, enantiomers thereof, or racemic mixtures thereof; or pharmaceutically acceptable salts thereof, are described. These compounds are useful as antiarrhythmic agents.

N-(heteroarylalkyl)acylanilide derivatives as antiarrhythmic agents

Compounds of the formula ##STR1## wherein R.sub.1 is ##STR2## the asterisk denotes the specific bonding orientation to the piperidine moiety; R.sub.2 is alkylene or --CO--(CH.sub.2).sub.n -- wherein n is 0 to 11; R.sub.3 and R.sub.4, independently, are hydrogen, halogen or lower alkoxy; and HET is pyridinyl, pyrimidinyl or imidazolyl, and salts thereof with pharmaceutically acceptable acids, are described. The compounds of formula I exhibit insulin lowering activity and are useful as antiobesity agents.

N-substituted diphenylpiperidines and antiobesity use thereof

Substituted isoquinolines of the formula ##STR1## wherein R is a lower alkoxy, n is the integer zero or 1, and

Substituted isoquinolines

Substituted isoquinolines of the formula ##STR1## wherein R is lower alkoxy, n is the integer zero or 1, and A is ##STR2## wherein R.sub.1 is phenyl, halophenyl, lower-alkylphenyl or lower-alkoxyphenyl, and pharmaceutically acceptable acid addition salts thereof, are described. The compounds of formula I are useful in the treatment of cerebral and cardiac ischemias.

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Hawthorne, NJ, United States of America

John G Mullin