Pfizer Corporation

Reinhard Sarges

John L Belletire

Harry R Howard, Jr

Donald E Kuhla

Rodney C Schnur

George R Evanega

Steven Wayne Goldstein

Saul B Kadin

Bernard Hulin

Hans E Wiedermann

Paul R Kelbaugh

Li-An Yeh

Albert Weissman

This invention relates to certain 5-acyl-2-oxo-indole-3-carboxamides useful as inhibitors of glycogen phosphorylase, methods of treating glycogen phosphorylase dependent diseases or conditions with such compounds and pharmaceutical compositions comprising such compounds. This invention also relates to pharmaceutical compositions comprising those 5-acyl-2-oxo-indole-3-carboxamides in combination with antidiabetes agents and methods of treating glycogen phosphorylase dependent diseases or conditions with such compositions.

Glycogen phosphorylase inhibitors

Certain novel 3-acyl-4-amino-8-alkoxyquinoline compounds have been prepared, including their pharmaceutically-acceptable salts. These compounds are useful for inhibiting gastric acid secretion in mammals and therefore, are of value in therapy as anti-ulcer agents. They are also useful for treating osteoporosis in a mammalian subject afflicted with said condition. Methods for preparing these compounds from known starting materials are provided.

Aminoquinoline derivatives

A series of novel 3-mono(substituted methyl)- and 3,3-di(substituted methyl)-2-oxo-indoline-1-alkanoic acid compounds have been prepared, including their lower alkyl esters and unsubstituted amide derivatives, as well as the base salts of said acids with pharmacologically acceptable cations. These compounds are useful in therapy as aldose reductase inhibitors for the control of certain chronic diabetic complications. Typical members include those compounds derived from 2-oxo-indoline-1-acetic acid wherein a 3,4-dichlorobenzyl or 3,4-dichloro-.alpha.-methylbenzyl moiety is substituted at 3-position of the molecule. Preferred member compounds include 3-(3,4-dichlorobenzyl)-2-oxo-indoline-1-acetic acid, 5-chloro-3-(3,4-dichlorobenzyl)-2-oxo-indoline-1-acetic acid, 3-(3,4-dichlorobenzyl)-6-methoxy-2-oxo-indoline-1-acetic acid, 3-(3,4-dichlorobenzyl)-6-hydroxy-2-oxo-indoline-1-acetic acid and 3-(3,4-dichloro-.alpha.-methylbenzyl)-2-oxo-indoline-1-acetic acid. Methods for preparing these compounds from known starting materials are provided.

Indolinone derivatives

Imidazolidinedione derivatives in diabetes treatment

A series of novel spiro-deteroazolones derived from a 2,3-dihydropryrano[2,3-b]pyridine ring system have been prepared, including their pharmaceutically acceptable salts. These compounds are useful in therapy as aldose reductase inhibitors for the control of certain chronic diabetic complications. Typical member compounds include spiro-imides, spiro-oxazolidinediones, spiro-thiazolidinediones and spiro-imidazolidinediones derived from the aforesaid ring system. (4'S) (2'R)-6'-Chloro-2',3'-dihydro-2'-methyl-spiro-[imidazolidine-4,4'-4'H-pyra no[2,3-b]pyridine]-2,5-dione represents a typical and preferred member compound. Methods for preparing all these compounds from known starting materials are provided.

Azolidinedione derivatives

Certain substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones are highly potent gabaergic agents, valuable in the treatment of individuals suffering from schizophrenia or reversing the side effects of a previously or concurrently administered neuroleptic agent; or in the treatment of epilepsy. A wider class of substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones, together with 1-phenyl-3-(2-pyrrolidinylidene)-2(1H,3H)-indolones, and homologs thereof, are valuable in the treatment of anxiety.

Method of treating anxiety and depression with

4-arylsulfonyl-3,4-dihydro-2(1H)-quinoxalinone-1-alkanoic acids, esters,

Certain substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones are highly potent gabaergic agents, valuable in the treatment of individuals suffering from schizophrenia or reversing the side effects of a previously or concurrently administered neuroleptic agent; or in the treatment of epilepsy. A wider class of substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones, together with 1-phenyl-3-(2-pyrrolidinylidiene-2(1H,3H)-indolones, and homologs thereof, are valuable in the treatment of anxiety.

1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents

1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents

Certain novel 1-(substituted-alkyl)-3-(3-hydroxyphenyl)piperidine compounds, and the pharmeceutically-acceptable acid-addition salts thereof, possess pharmaceutical activity as neuroleptic agents, and they are useful for treating psychotic disorders, e.g. schizophrenia, in human subjects. In particular, they are useful for alleviating such symptoms as anxiety, agitation, excessive aggression, tension and social or emotional withdrawal in psychotic patients. Certain 3-(3-methoxyphenyl)piperidine compounds are useful as chemical intermediates to the aforementioned neuroleptic agents.

Intermediates for 1,3-disubstituted piperidine compounds as neuroleptic

A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention.

[1,2,4]Triazolo[4,3-a]quinoxaline-4-amine derivatives

Certain novel 1-(substituted-alkyl)-3-(3-hydroxyphenyl)piperidine compounds, and the pharmaceutically-acceptable acid-addition salts thereof, possess pharmaceutical activity as neuroleptic agents, and they are useful for treating psychotic disorders, e.g. schizophrenia, in human subjects. In particular, they are useful for alleviating such symptoms as anxiety, agitation, excessive agression, tension and social or emotional withdrawal in psychotic patients. Certain 3-(3-methoxyphenyl)piperidine compounds are useful as chemical intermediates to the aforementioned neuroleptic agents.

1,3-disubstituted piperidine compounds as neuroleptic agents

A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention and a method of using the compounds in the treatment of depression and fatigue.

Growing community of inventors

Mystic, CT, United States of America

Reinhard Sarges