Hoffmann-la Roche Inc.

Leo Berger

Gary L Olson

John William Scott

Robert August Schmidt

Alfred J Corraz

David Richard Parrish

John T Plati

Albert Ziering

Willy Leimgruber

Thomas F Mowles

Wallace M Dairman

Fausto Eugenio Schenker

Herman W Baruth, Jr

Jerry Sepinwall

The invention relates to long-acting depot producing antipsychotic pyrroloisoquinolinyl-dimethyloxoalkyl alkanoates of the formula ##STR1## wherein R.sub.1 and R.sub.2 independently, are hydrogen, alkyl of 1 to 4 carbon atoms, cycloalkyl or alkenyl, or taken together are alkylene of 3 to 6 carbon atoms; and R.sub.3 is hydrogen, alkyl, hydroxyalkyl, phenylhydroxyalkyl, halophenylhydroxyalkyl, alkylphenylhydroxyalkyl, alkoxyphenylhydroxyalkyl, alkoxyalkyl, aryloxyhydroxyalkyl, alkoxyhydroxyalkyl, acyloxyalkyl, arylcarbonylalkyl, alkoxycarbonylalkyl, aralkyl, alkenyl, alkylcycloalkyl, alkynyl, thienylalkyl, furylalkyl, arylcarboxamidoalkyl, acylalkyl, cyclic-alkyloxoalkyl, cyclic-alkylhydroxyalkyl, alkenyloxyalkyl, aralkenyl, aryloxyalkyl, or aryl-N-imidazolonylalkyl; R.sub.4 is alkyl; and n is the integer 2 or 3, their corresponding optical isomers, geometric isomers, and mixtures thereof, and the pharmaceutically acceptable acid additional salts. The compounds of formula I are useful as antipsychotic agents.

Pyrroloisoquinolinyl-dimethyloxoalkyl alkonoates and their use as

Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl or acyl; R.sub.2 and R.sub.3 independently are lower alkyl, aralkyl or alkenyl or R.sub.2 and R.sub.3 together form a ring of 5 to 8 carbon atoms; R.sub.4 is phenyl, substituted phenyl, cyclohexyl, substituted cyclohexyl, cyclopentyl, substituted cyclopentyl, cycloheptyl, or substituted cycloheptyl; R.sub.5 is hydrogen or lower alkyl; R.sub.6 is hydrogen, lower alkyl or acyl; and pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I and pharmaceutically acceptable acid addition salts thereof are anti-emetic agents which lack central nervous system side effects.

Substituted piperidinomethylindolone and cyclopent(b)indolone derivatives

A method of producing analgesia by administering an opiate alkaloid such as morphine, codeine, oxycodone or a pharmaceutically acceptable acid addition salt thereof together with a carbazole compound, 6-chloro-.alpha.-methyl-carbazole-2-acetic acid, or a salt thereof with a pharmaceutically acceptable base and composition therefor.

Analgesic composition containing a mixture of

The present invention is directed to a compound having the formula ##STR1## which is used as an intermediate in the preparation of octahydro-1H-pyrrolo[2,3-g]isoquinolines.

1,2,3,4,4a,7-Hexahydro-6,8-dimethoxy-2-methyl isoquinoline

Neuroleptically active cycloalka[4,5]pyrrolo[2,3-g]isoquinolines of the formula ##STR1## wherein n, R.sub.1, R.sub.2 and X are as hereinafter set forth, and intermediates therefore are described.

Cycloalka[4,5]pyrrolo[2,3-g]isoquinolines

Neuroleptically active octahydro-1H-pyrrolo[2,3-g]isoquinolines of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and X are as hereinafter set forth, are described.

Octahydro-2-methyl-isoquinoline-6,8-dione

Neuroleptically active cycloalka[4,5]pyrrolo[2,3-g]isoquinolines of the formula ##STR1## wherein n, R.sub.1, R.sub.2 and X are as hereinafter set forth, are described.

Dibenzothiophenes of the formula ##STR1## wherein R, R.sub.1 and R.sub.2 are as hereinafter described, prepared, inter alia, from the correspondingly substituted thiophenol and haloketocyclohexane are described. The dibenzothiophenes of the invention are useful antiinflammatory, analgesic and antirheumatic agents.

Dibenzothiophenes

Octahydro-1H-pyrrolo[2,3-g]isoquinolines

A process for preparing 6-chloro-.alpha.-methylcarbazole-2-acetic acid and esters thereof by the steps of:

Process of making a carbazole acetic acid

Dibenzofurans of the formula ##STR1## wherein R, R.sub.1 and R.sub.2 are as hereinafter described prepared, inter alia, from the correspondingly substituted phenol and haloketocyclohexane are described. The dibenzofurans of the invention are useful anti-inflammatory, analgesic and anti-rheumatic agents.

Halo-3-dibenzofuran alkanonitriles

Dibenzofurans of the formula ##STR1## wherein R, R.sub.1 and R.sub.2 are as hereinafter described, prepared, inter alia, from the correspondingly substituted phenol and haloketocyclohexane are described. The dibenzofurans of the invention are useful antiinflammatory, analgesic and anti-rheumatic agents.

Certain 8-halodibenzofuran-3-alkanols

6-Chloro-1,2,3,4-tetrahydrocarbazole-2-one

A process for the preparation of 6-chloro-.alpha.-methylcarbazole-2-acetic acid from 6-chloro-.alpha.-hydroxy-.alpha.-methylcarbazole-2-acetic acid and/or 6-chloro-.alpha.-methylene-2-carboxylic acid, is described. The preparation of intermediates, such as, 6-chloro-.alpha.-hydroxy-.alpha.-methylcarbazole-2-acetic acid and lower alkyl carbazole-2-oxalate, inter alia, is also described.

Growing community of inventors

Montclair, NJ, United States of America

Leo Berger