Merrell Dow Pharmaceuticals

Merrell Pharmaceuticals, Inc.

Richardson-merrell Inc.

Aventis Pharma Limited

Jules Freedman

Mark W Dudley

Alan J Bitonti

Sai P Sunkara

Bruce M Baron

Richard C Dage

Frank P Palopoli

Sai Prasad Sunkara

The present invention provides novel compounds such as certain aryloxy indanamines which are useful as anti-depressants and as inhibitors of synaptic norepinephrine and serotonin uptake. The present invention also provides an improvement in the treatment of depression which comprises inhibiting synaptic serotonin and epinepherine uptake.

Antidepressants

Certain triphenylpiperidines reverse drug resistance in multi-drug resistant tumors. These compounds apparently function by inhibiting a p-glycoprotein pump which becomes activated in late stage tumor development and which is inherently present in tumors from certain origins.

Reversal of multi-drug resistance by triphenyl-azacycloalkane derivatives

Diarylalkyl piperidines useful as multi-drug resistant tumor agents

The present invention provides novel aryloxy indanamines which are useful as anti-depressants and as inhibitors of synaptic norepinephrine and serotonin uptake.

The present invention is directed to a new class of arylalkoxyphenoxy-imidazoline compounds and their use for the treatment of depression, anxiety, hypertension, and migraine headaches.

Arylalkoxyphenoxy-imidazoline compounds

Novel bis-dibenzoazepine compounds useful in the treatment of malaria and drug-resistant malaria.

Bis-dibenzoazepine compounds

The present invention provides novel aryloxy indanamines of the formula ##STR1## wherein n, p and q are each independently 0, 1 or 2,

Drug-resistant protozoal infection, particularly, drug-resistant malarial infection in humans, can be effectively treated with standard antiprotozoal agents if administered in conjunction with a phenoxyamino-substituted benzocycloalkane derivative.

Phenoxy and phenylthio, amino substituted benzocycloalkane derivatives

The present invention is directed to a new class of phenoxy-heterocyclic compounds and to their use as anti-depressants and as anxiolytics.

Phenoxy-heterocyclic compounds

Derivatives of 2H-[1]benzoxepino[5,4-b]-1,4-oxazine, such as trans-3,4,4a,5,6,11b-hexahydro-10-methoxy-2H-[1]benzoxepino[5,4-b]-1,4-oxa zine, are prepared by acylating a trans-4-amino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol, cyclizing the resulting chloroacetamido alcohol, reducing the 1,4-oxazine-3(4H)-one so obtained, acylating the resulting 2H-[1]-benzoxepino[5,4-b]-1,4-oxazine, and reducing the N-acryl-2H-[1]benzoxepino[5,4-b]-1,4-oxazine so obtained. The novel compounds disclosed herein possess useful antihypertensive properties.

2H-[1]benzoxepino[5,4-b]-1,4-oxazine derivatives

The compounds are 11-aminoalkylmorphanthridin-11-ols which are useful as antidepressant agents. The compounds disclosed are 11-(3-dimethylaminopropyl)morphanthridin-11-ol and 2-chloro-11-(3-dimethylaminopropyl)-5,6-dihydromorphanthridin-11-ol.

11-Aminoalkylmorphanthridin-11-ols

The inventive method comprises administering a morphanthridine to an animal to effect the lowering of inflammation. Representative of the compounds that can be used in the method are trans-5-acetyl-2-bromo-5,6-dihydro-11-(3-dimethylaminopropylidene)-morphan thridine and trans-2-bromo-11-(3-dimethylaminopropylidene)-5,6-dihydro-5-propionylmorph anthridine.

Method of treating inflammation with morphanthridines

Pure cis or trans-6-substituted-11-aminoalkylidenemorphanthridines are prepared by treating the corresponding cis or trans-5,6-dihydromorphanthridines with oxygen in the presence of a platinum on carbon catalyst. Among the compounds prepared are:

Cis or trans-6-substituted-11-aminoalkylidenemorphanthridines

Pure cis and trans-6-substituted-11-aminoalkylidene-5,6-dihydromorphanthridines are prepared by treating the morphanthridines unsubstituted in the 6-position with a Grignard reagent in a suitable solvent such as tetrahydrofuran. Among the compounds disclosed are:

Growing community of inventors

Cincinnati, OH, United States of America

Jules Freedman