Pfizer Corporation

Bayer Aktiengesellschaft

Charles A Harbert

Michael Ross Johnson

Lawrence S Melvin, Jr

Thomas H Althuis

Willard M Welch, Jr

Joseph G Lombardino

Allen R Kraska

B Kenneth Koe

Jacob J Plattner

James R Tretter

Willard H Welch, Jr

Novel trans-isomeric derivatives of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine are useful as antidepressant agents. These novel compounds act to block the synaptosomal uptake of norepinephrine and serotonin (5-hydroxy-tryptamine), thereby alleviating abnormalities at central receptor sites. The preferred embodiment is the enantiomer trans-(1R)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalen amine and its pharmaceutically acceptable acid addition salts.

Antidepressant derivatives of

Novel cis-isomeric derivatives of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine are useful as antidepressant agents. These novel compounds act to block the synaptosomal uptake of serotonin (5-hydroxy-tryptamine), thereby alleviating serotonin abnormalities at central receptor sites. The preferred embodiment is the enantiomer cis-(1S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenam ine and its pharmaceutically acceptable acid addition salts.

A series of 4-(2-hydroxyethylthiomethyl)pyridines and related compounds, and their pharmaceutically acceptable acid addition salts, having immunoregulatory activity are disclosed. Preferred compounds include 4-(2-hydroxyethylthiomethyl)pyridine itself, as well as 4-(2-hydroxy-1-propylthiomethyl)pyridine, 4-(3-hydroxy-2-butylthiomethyl)pyridine, the acetate esters corresponding to the above compounds, and 4-(2,3-dihydroxy-1-propylthiomethyl)pyridine.

Certain 4-(2-hydroxyethylthiomethyl)pyridines and derivatives thereof

A series of 4-(2-carboxymethylthiomethyl)pyridines and related compounds, and their pharmaceutically acceptable salts, are disclosed as having immunoregulatory activity. Preferred compounds include 4-(2-carboxymethylthiomethyl)pyridine [alternatively named 2-(4-picolylthio)acetic acid] and (C.sub.1 -C.sub.4)alkyl esters thereof, and 4-(1-formylmethylthiomethyl)-pyridine [alternatively named 2-(4-picolylthio)acetaldehyde] and bis(C.sub.1 -C.sub.4)alkyl or cyclic acetals thereof. These acids, esters, aldehydes and acetals also have utility as intermediates in the synthesis of the corresponding 4-(2-hydroxyethylthiomethyl)pyridines.

Method of regulating the immune response with pyridine derivatives

Derivatives of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]-indole and of (+)enantiomeric, mixtures of (+) and (-)enantiomeric or (.+-.)racemic 2,3,4,4a,5,9b-hexahydro-4a,9b-trans-1H-pyrido[4,3-b]indole, substituted at the 5-position with an aryl group and at the 2-position with a carbonylaminoalkyl group or an aminoalkyl group, are neuroleptic agents useful in the treatment of certain psychoses and neuroses.

Hexahydro-trans-pyridoindole

Hexahydro-trans- and tetrahydropyridoindole neuroleptic agents

Derivatives of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and of (+)enantiomeric, mixtures of (+) and (-)enantiomeric or (.+-.)racemic 2,3,4,4a,5,9b-hexahydro-4a,9b-trans-1H-pyrido[4,3-b]indole, substituted at the 5-position with an aryl group and at the 2-position with a carbonylaminoalkyl group or an aminoalkyl group, are neuroleptic agents useful in the treatment of certain psychoses and neuroses.

Cycloalkanones, cycloalkanols and unsaturated analogs thereof, each of which has at the 3-position a 2-hydroxy-4-substituted phenyl group wherein the 4-position substituent is alkyl which can have an oxygen atom as part of the chain, or aralkyl which can have an oxygen atom as part of the alkyl chain, their use for pharmacological and medicinal purposes, intermediates therefor and processes for their preparation.

3-(2-Hydroxy-4-(substituted)phenyl)-cycloalkanone and cycloalkanol

Azacycloalkanes, and derivatives thereof, including unsaturated analogs, each of which has at the 3-position a 2-hydroxy-4-substituted phenyl group wherein the 4-position substituent is alkyl which can have an oxygen atom as part of the chain, or aralkyl which can have an oxygen atom as part of the alkyl chain, their use for pharmacological and medicinal purposes, intermediates therefor and processes for their preparation.

3-[2-Hydroxy-4-(substituted)phenyl]azacycloalkanols and derivatives

A series of 4-(2-carboxymethylthiomethyl)pyridines and related compounds, and their pharmaceutically acceptable salts, are disclosed as having antiinflammatory and immunoregulatory activity. Preferred compounds include 4-(2-carboxymethylthiomethyl)pyridine [alternatively named 2-(4-picolylthio)acetic acid] and (C.sub.1 -C.sub.4)alkyl esters thereof, and 4-(1-formylmethylthiomethyl)pyridine [alternatively named 2-(4-picolylthio)-acetaldehyde] and bis(C.sub.1 -C.sub.4)alkyl or cyclic acetals thereof. These acids, esters, aldehydes and acetals also have utility as intermediates in the synthesis of the corresponding 4-(2-hydroxyethylthiomethyl)pyridines.

Certain pyridine methylthio acetaldehyde derivatives and non-cyclic and

Medicinal agents classed as 2-(aminoalkyl or amidoalkyl)-5-aryl-hexahydro-trans-4a,9b-1(H)-pyrido-[4,3-b]indole derivatives have been synthesized and found to have neuroleptic activity.

Hexahydro-trans-pyridoindole neuroleptic agents

Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, benzyl, benzoyl, alkanoyl of 1 to 5 carbon atoms or --CO--(CH.sub.2).sub.p --NR'R' wherein p is 0 or an integer from 1 to 4; each of R' and R' when taken individually is hydrogen or alkyl of 1 to 4 carbon atoms; R' and R' when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring selected from piperidino, pyrollo, pyrrolidino, morpholino and N-alkylpiperazino having from 1 to 4 carbon atoms in the alkyl group;

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Waterford, CT, United States of America

Charles A Harbert