Hoffmann-la Roche Inc.

Gary L Olson

Gabriel G Saucy

Leo Berger

Jefferson Wright Tilley

Waleed Danho

Shian-Jan Shiuey

Thomas F Mowles

Rolf Wagner

Wallace M Dairman

Galbriel Saucy

David J Nelson

The invention is directed to novel CCK analogs wherein Tryptophan and/or Phenylalamine are substituted with a radical which provides enhanced appetite suppressant activity to the peptide.

CCK analogs with appetite regulating activity

[(5-oxo-2-pyrrolidinyl)methyl]cyclohexaneacetamides of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl or aryl-lower alkyl; R.sub.2 is hydrogen, lower alkyl, aryl, aryl-lower alkyl, ##STR2## wherein R.sub.5 and R.sub.6 are hydrogen, lower alkyl or aryl-lower alkyl; R.sub.3 and R.sub.4, independently, are hydrogen, lower alkyl, or aryl-lower alkyl; and enantiomers, diastereomers, and racemates thereof, and, when R.sub.2 is ##STR3## pharmaceutically acceptable acid addition salts thereof, are described. The compounds of formula I exhibit cognitive enhancement and antiamnestic activity and are therefore useful, for example, in treating memory deficits associated with Alzheimer's disease or age-associated memory impairment.

[(5-oxo)-2-pyrrolidinyl)methyl]cyclohexaneacetamides, compositions and

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

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.

A synthesis of Vitamin E has the condensation of 2,4-pentanediene and 1,2-epoxy-2,6,10,14-tetramethylpentadecane including intermediates in this synthesis which uses base catalyzed condensations of aliphatic compounds to construct the Vitamin E molecule from aliphatic precursors.

Synthesis of vitamin E and quinone intermediates

A novel process for the preparation of esters of 5-formyl-3-methyl-2,4-pentadien-1-ol which employs as starting materials 2-substituted-3-methyl-6-alkoxy-3,6-dihydro-2H-pyrans. Novel intermediates are also disclosed.

Process for the preparation of esters of

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

1 A synthesis of Vitamin E has the condensation of 2,4-pentanediene and 1,2-epoxy-2,6,10,14-tetramethylpentadecane including intermediates in this synthesis which uses base catalyzed condensations of aliphatic compounds to construct the Vitamin E molecule from aliphatic precursors.

Synthesis of vitamin E

A novel process for the preparation of polyene aldehydes which employs as starting materials, substituted 2H pyrans. Novel substituted 2H pyrans and polyene intermediates are also disclosed.

Process for preparation of polyene aldehydes

A process for producing vitamin A esters, vitamin A aldehyde and vitamin A acid esters from esters of 3,7-dimethyl-9-(1-hydroxy-2,2,6-trimethylcyclohexyl)-nona-2,4,6-trien-8-yn -1-ol and 3,7-dimethyl-9-(1-hydroxy-2,2,6-trimethylcyclohexyl)-nona-2,4,6-trien-8-yn oic acid including intermediates in this process.

Growing community of inventors

Westfield, NJ, United States of America

Gary L Olson