Janssen Pharmaceutica Nv

Other

Janssen Pharmaceutica

Robert William Kavash

Jan Heeres

Donald William Ludovici

Michael Joseph Kukla

Wei He

Henry Joseph Breslin

Paul Adriaan Jan Janssen

Lucien Maria Henricus Koymans

Koen Jeanne Alfons Van Aken

Bart L De Corte

Chaozhong Cai

Chih Yung Ho

Marc René De Jonge

Bart Lieven Daniel De Corte

Marc Ren&eacute; De Jonge

Marc Rene De Jonge

Alain Krief

Koenraad Jozef Lodewijk Marcel Andries

Frederik Frans Desir&eacute; Daeyaert

Bart Lieven De Corte

Koen Jeanne Van Aken

Paul Adriaan Janssen

Paul A Janssen

Ruben Gerardus George Leenders

Frank Xavier Jozef Herwig Arts, Legal Representative

Frederik Frans Daeyaert

Lucien Maria Koymans

Ruben Gerardus Leenders

Paul Andriaan Jan Janssen

Bart De Cort

The present invention is directed to novel opioid receptor modulators of Formula (I).  The invention further relates to methods for preparing such compounds, pharmaceutical compositions containing them, and their use in the treatment of disorders that may be ameliorated or treated by the modulation of opioid receptors.

Compounds as opioid receptor modulators

The present invention is directed to novel opioid receptor modulators of Formula (I). The invention further relates to methods for preparing such compounds, pharmaceutical compositions containing them, and their use in the treatment of disorders that may be ameliorated or treated by the modulation of opioid receptors.

This invention concerns the use of compounds of formula the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a=a-a=a- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; Ris hydrogen, aryl, formyl, Calkylcarbonyl, Calkyl, Calkyloxycarbonyl, substituted Calkyl, or substituted CalkyloxyCalkylcarbonyl; each Rindependently is hydroxy, halo, optionally substituted Calkyl, Calkenyl or Calkynyl, Ccycloalkyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkylamino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted Calkyl, Calkenyl, Calkynyl or Ccycloalkyl; or L is &#x2014;X&#x2014;Rwherein Ris optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is &#x2014;NR&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;N&#x2550;N&#x2014;, &#x2014;O&#x2014;, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;CHOH&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014; or &#x2014;S(&#x2550;O)&#x2014;; Q is hydrogen, Calkyl, halo, polyhalo-Calkyl or an optionally substituted amino group; Y represents hydroxy, halo, Ccycloalkyl, optionally substituted Calkyl, Calkenyl or Calkynyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

HIV replication inhibiting pyrimidines

This invention concerns the use of compounds of formula the N-oxides, pharmaceutically acceptable addition salts, quaternary amines, stereochemically isomeric forms thereof, wherein -a=a-a=a- forms phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl with the attached vinyl group; n is 0 to 5; Ris hydrogen, aryl, formyl, Calkylcarbonyl, Calkyl, Calkyloxycarbonyl, substituted Calkyl, substituted CalkyloxyCalkylcarbonyl; Ris hydroxy, halo, optionally substituted Calkyl, Calkenyl or Calkynyl, Ccycloalkyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)R, 5-membered heterocyclic ring; L is optionally substituted Calkyl, Calkenyl, Calkynyl or Ccycloalkyl; or &#x2014;X&#x2014;R; Q is hydrogen, Calkyl, halo, polyhalo-Calkyl, optionally substituted amino group; Y represents hydroxy, halo, Ccycloalkyl, optionally substituted Calkyl, Calkenyl or Calkynyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono-or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, 13 NHC(&#x2550;O)R,&#x2014;C(&#x2550;NH)R, aryl; for the treatment of subjects suffering from HIV infection.

The present invention concerns compounds of formula (A)(A)N&#x2014;R(I), the N-oxide forms, the pharmaceutically acceptable addition salts, the quaternary amines and stereochemically isomeric forms thereof, wherein Ris substituted Calkyl; &#x2014;S(&#x2550;O)&#x2014;R; &#x2014;S(&#x2550;O)&#x2014;R; Calkylcarbonyl; optionally substituted CalkyloxycarbonylCalkylcarbonyl; with Rbeing Calkyl, arylor Het; (A)(A)N&#x2014; is the covalently bonded form of the corresponding intermediate of formula (A)(A)N&#x2014;H, which is a HIV replication inhibiting pyrimidine of formula 

Prodrugs of HIV replication inhibiting pyrimidines

This invention is directed towards novel compounds as opioid receptor modulators, antagonists, and agonists useful for the treatment of opioid modulated disorders such as pain and gastrointestinal disorders.

Piperidines as opioid receptor modulators

This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, provided that when Q is halo then Z is N; or when Q is polyhaloCalkyl then Y is hydrogen or Calkyl; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

HIV replication inhibitors

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Glenside, PA, United States of America

Robert William Kavash