Aventis Pharmaceuticals Inc.

Aventis Hoklings Inc.

George Lee

David Fink

John G Jurcak

Yulin Chiang

Kenneth J Bordeau

Matthias Urmann

Horst Hemmerle

James Hendrix

Gregory Shutske

Nicola Collar

Sharon Anne Jackson

Thaddeus Nieduzak

Paul Angell

James P Carey

Joseph T Strupczewski

Raymond W Kosley, Jr

Nicholas J Hrib

Brian S Freed

Gregory H Merriman

Barbara S Rauckman

Jean-Francois Sabuco

Timothy A Ayers

Reda Hanna

Juergen Mueller-Lehar

Franz J Weiberth

Silke Dubberke

Roland Utz

Jospeh T Strupczewski

Jean-Fancois Sabuco

The invention relates to heterocyclic substituted carbonyl derivatives that display selective binding to dopamine Dreceptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine Dreceptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine Dreceptors.

[object Object]

The compounds are of the class thienoisoxazolyl- and thienylpyrrazolyl-phenoxy substituted propyl derivatives, useful as Dantagonists. Said compounds are useful for the treatment of medical conditions mediated by inhibition of Dreceptor. These conditions comprise, for example, Attention Deficit Hyperactivity Disorder, Obsessive-Compulsive Disorder, Psychoses, Substance Abuse, Substance Dependence, Parkinson's Disease, Parkinsonism, Tardive Diskinesia, Gilles de la Tourette Syndrome, Conduct Disorder, and Oppositional Defiant Disorder. A further aspect of the invention is to provide a pharmaceutical composition, intermediates, and a method of making said class of compounds.

An improved process for the preparation of N-amino nitrogen heterocyclic compounds is disclosed and claimed. In an embodiment of this invention, a compound of the formula (VI) is prepared starting from the corresponding indole derivative by way of N-amination and subsequently forming an hydrazone by the reaction with a keto compound in a single step. Further reduction of the hydrazone and subsequent coupling with a pyridine compound affords the compound of formula VI or a suitable salt thereof. 

Process for the preparation of N-amino substituted heterocyclic compounds

The compounds are of the class of thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives, useful as Dantagonists. Said compounds are useful for the treatment of medical conditions mediated by inhibition of Dreceptor. These conditions comprise, for example, Attention Deficit Hyperactivity Disorder, Obsessive-Compulsive Disorder, Psychoses, Substance Abuse, Substance Dependence, Parkinson's Disease, Parkinsonism, Tardive Diskinesia, Gilles de la Tourette Syndrome, Conduct Disorder, and Oppositional Defiant Disorder. A further aspect of the invention is to provide a pharmaceutical composition, intermediates, and a method of making said class of compounds.

Growing community of inventors

Somerville, NJ, United States of America

George Lee