Hoechst Roussel Pharmaceuticals

American Hoechst Corporation

Hoechst Marion Roussel

Titan Pharmaceuticals, Inc.

Hoechst-roussel Incorporated

Richard C Allen

Joseph T Strupczewski

Brian S Freed

Thomas B Lee

R Richard Hamer

Arthur R McFadden

Beth A Gardner

Lawrence L Martin

John I White

Gregory M Shutske

Raymond W Kosley, Jr

David G Wettlaufer

Linda L Setescak

David M Fink

Marc N Agnew

Richard C Effland

Joseph T Klein

Grover C Helsley

Gerard J O'Malley

Solomon S Klioze

Bettina Spahl

Edward J Glamkowski

Denise M Flanagan

James M Fortunato

Michael Cornfeldt

V Brian Anderson

The invention provides methods for the treatment of abnormal psychiatric states, particularly the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) of antipsychotic drugs. The inventive methods relate to the administration of therapeutic cells (which produce dopamine or dopamine precursors) adhered to support matrices to subjects suffering from the negative symptoms of schizophrenia and/or EPS. The therapeutic cells may be coadministered with cells which protect the therapeutic cells from immune rejection and/or cells which produce neurotrophic factors which improve the viability of the therapeutic cells.

Methods of treating schizophrenia

This invention relates to N-hydroxy-dibenz�b,e!oxepinalkylamines, N-hydroxy-dibenz�b,e!oxepinalkanoic acid amides and related heterocyclic analogues of the formula ##STR1## where X together with the carbon atoms to which it is attached forms a benzene or thiophene ring; W and Z are independently hydrogen, halogen, loweralkyl, or trifluoromethyl; R.sup.1 is hydrogen, arylloweralkyl, loweralkoxycarbonyl, loweralkylcarbonyl, arylcarbonyl or arylloweralkylcarbonyl; R.sup.2 is loweralkyl, cycloalkyl, arylloweralkyl, loweralkoxycarbonyl, loweralkylcarbonyl, arylcarbonyl or arylloweralkylcarbonyl; m is 0 or 1 and n is an integer of 0 to 4 or the pharmaceutically acceptable salts thereof. The compounds of this invention are useful as analgesics and topical antiinflammatory agents for the treatment of various dermatoses and agents for the treatment of conditions where accumulation of cyclooxygenase and/or lipoxygenase metabolites is a causative factor.

N-hydroxy-dibenz�b,e!oxepinalkylamines,

N-hydroxy-dibenz �b,e!oxepinalkylamines, N-hydroxy-dibenz

This invention relates to alkylamino and alkyl amino alkyl diarylketones of the formula ##STR1## where Ar is aryl of the formula ##STR2## where V is hydrogen, halogen, loweralkyl, loweralkoxy, CF.sub.3, NO.sub.2 and u is an integer of 1 to 3; X and Y are independently CH.sub.2 --, --CF.sub.2 -- or --CHF--; Z and W are independently --CH.sub.2 --, --O--, --CHOH--, or --CHF--; m, n, p, q and t are integers which are independently 0 or 1; R.sub.1 is H or loweralkyl; R.sub.2 and R.sub.3 are loweralkyl; and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic agents and as agents for alleviating various memory dysfunctions, characterized by a decreased cholinergic function, such as Alzheimer's disease.

Alkylamino-and alkylamino alkyl diarylketones

Novel 2,6-methano-1,3-benzodiazocines, intermediates, processes for the preparation thereof, and methods for alleviating pain and for alleviating various memory dysfunctions characterized by a decreased cholinergic function, such as Alzheimer's disease, utilizing compounds or compositions thereof are disclosed.

Process of preparing 2,6-methano-1,3-benzodiazocine compounds

This invention relates to pyrrolo[2,3-b]indole ketones of the formula ##STR1## where R.sub.1 is loweralkyl, aryl or arylloweralkyl; R.sub.2 is hydrogen, halogen or loweralkyl; R.sub.3 is hydrogen or loweralkyl; R.sub.4 is loweralkyl or arylloweralkyl; R.sub.5 is hydrogen, loweralkyl, loweralkenyl, loweralkynyl, arylloweralkyl, formyl, loweralkylcarbonyl, arylloweralkylcarbonyl or loweralkoxycarbonyl; Y is hydrogen, loweralkyl or loweralkoxy; the pharmaceutically acceptable addition salts thereof, and where applicable, the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention are useful in the treatment of memory impairment characterized by a cholinergic deficit such as that associated with electroshock-induced amnesia and Alzheimer's disease and other senile dementia.

Pyrrolo[2,3-b]indole-ketones and analogs

This invention relates to p-acylaminophenoxycarbamates having the formula ##STR1## where R.sub.1 and R.sub.2 are each independently hydrogen, loweralkyl, aryl and arylloweralkyl; R.sub.3 is hydrogen, loweralkyl, arylloweralkyl; R.sub.4 is hydrogen, loweralkyl, formyl, alkylcarbonyl, arylloweralkyl, phenylcarbonyl, arylloweralkylcarbonyl, substituted phenylcarbonyl, pyridylcarbonyl, and substituted pyridylcarbonyl with the proviso that if R.sub.4 contains a carbonyl group directly attached to the oxygen of the N-O moiety, R.sub.3 cannot be hydrogen; or R.sub.3 and R.sub.4 taken together from a heterocyclic ring selected from the group consisting of imidazole or loweralkylimidazole; X is hydrogen, halogen, hydroxy, loweralkyl, loweralkoxy, nitro, amino or trifluoromethyl; and p is an integer selected from 0 and 1; the pharmaceutically acceptable acid addition salts thereof, and where applicable, the geometric and stereoisomers and racemic mixtures thereof. The compounds of this invention display utility as analgesics.

Method of using p-acylaminophenoxycarbamates and derivatives as

This invention relates to alkylamino and alkyl amino alkyl diarylketones of the formula ##STR1## where Ar is aryl of the formula ##STR2## where V is hydrogen, halogen, loweralkyl, loweralkoxy, CF.sub.3, NO.sub.2 and u is an integer of 1 to 3; X and Y are independently CH.sub.2 --, --CF.sub.2 -- or --CHF--; Z and W are independently --CH.sub.2 --, --O--, --CHOH--, or --CHF--; m, n, p, q and t are integers which are independently 0 or 1, R.sub.1 is H or loweralkyl; R.sub.2 and R.sub.3 are loweralkyl; and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic agents and as agents for alleviating various memory dysfunctions, characterized by a decreased cholinergic function, such as Alzheimer's disease.

Alkylamino- and alkylamino alkyl diarylketones and pharmaceutical

Novel 2,6-methanopyrrolo-3-benzazocines, intermediates, processes for the preparation thereof, and methods for alleviating pain utilizing compounds or compositions thereof are disclosed.

2,6-methanopyrrolo-3-benzazocines

This invention relates to p-acylaminophenoxycarbamates having the formula ##STR1## where R.sub.1 and R.sub.2 are each independently hydrogen, loweralkyl, aryl and arylloweralkyl; R.sub.3 is hydrogen, loweralkyl, aryllowerallkyl; R.sub.4 is hydrogen, loweralkyl, formyl, alkylcarbonyl, arylloweralkyl, phenylcarbonyl, arylloweralkylcarbonyl, substituted phenylcarbonyl, pyridylcarbonyl, and substituted pyridylcarbonyl with the proviso that if R.sub.4 contains a carbonyl group directly attached to the oxygen of the N-O moiety, R.sub.3 cannot by hydrogen; or R.sub.3 and R.sub.4 taken together form a heterocyclic ring selected from the group consisting of imidazole or loweralkylimidazole; X is hydrogen, halogen, hydroxy, loweralkyl, loweralkoxy, nitro, amino or trifluoromethyl; and p is an integer selected from 0 and 1; the pharmaceutically acceptable acid addition salts thereof, and where applicable, the geometric and stereoisomers and racemic mixtures thereof. The compounds of this invention display utility as analgesics.

P-acylaminophenoxycarbamates and derivatives

2,6-methano-1,3-benzodiazocine compounds

There are disclosed various compounds of the formula below, ##STR1## where X is O, S, NH, N-loweralkyl, or N-arylloweralkyl;

Hexahydropyrrolo(2,3-B)indole carbamates, ureas, amides and related

2,6-methaopyrrolo-3-benzazocine dione derivatives as intermediates for

2,6-methano-1,3-benzodiazocine compounds which have useful

This invention relates to alkylamino and alkyl amino alkyl diarylketones of the formula ##STR1## where Ar is aryl of the formula ##STR2## where V is hydrogen, halogen, loweralkyl, loweralkoxy, CF.sub.3, No.sub.2 and u is an integer of 1 to 3; X and Y are independently CH.sub.2 --, --CH.sub.2 -- or --CHF--; Z and W are independently --CH.sub.2 --, --O--, --CHOH--, or --CHF--; m, n, p, q and t are integers which are independently 0 or 1; R.sub.1 is H or loweralkyl; R.sub.2 and R.sub.3 are loweralkyl; and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic agents and as agents for alleviating various memory dysfunctions, characterized by a decreased cholinergic function, such as Alzheimer's disease.

Alkylamino- and alkylamino alkyl diarylketones

Growing community of inventors

Flemington, NJ, United States of America

Richard C Allen