Janssen Pharmaceutica Nv

Other

Janssen Pharmaceutica

Bart Lieven Daniel De Corte

Jan Heeres

Li Liu

Henry Joseph Breslin

Donald William Ludovici

Paul Adriaan Jan Janssen

Lucien Maria Henricus Koymans

Michael Joseph Kukla

Koen Jeanne Alfons Van Aken

Marc René De Jonge

Robert William Kavash

Ashis Kumar Saha

David William End

Alain Krief

Ruben Gerardus George Leenders

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

a prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; &#x2550;Z&#x2014;Z&#x2550;Z&#x2014; represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH), wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond; Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle.

Triazoles as farnesyl transferase inhibitors

A prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; =Z-Z=Z- represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH)wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond; Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle. 

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

a prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; &#x2550;Z&#x2014;Z&#x2550;Z&#x2014; represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH)wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond, Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle.

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

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Southampton, PA, United States of America

Bart Lieven Daniel De Corte