Substituted nicotinamides and analogs as activators of...

C - Chemistry – Metallurgy – 07 – D

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C07D 213/82 (2006.01) A61K 31/341 (2006.01) A61K 31/44 (2006.01) A61K 31/4965 (2006.01) C07D 207/34 (2006.01) C07D 213/75 (2006.01) C07D 239/28 (2006.01) C07D 241/24 (2006.01) C07D 241/28 (2006.01) C07D 307/68 (2006.01) C07D 401/12 (2006.01) C07D 405/12 (2006.01)

Patent

CA 2397493

The present invention is directed to substituted nicotinamides and analogs thereof, represented by Formula (V) or a pharmaceutically acceptable salt or prodrug thereof, wherein: Ar' and Ar are independently optionally substituted aryl or optionally substituted heteroaryl, provided that the ring structure of said optionally substituted heteroaryl comprises not more than two nitrogen atoms; and R11 is hydrogen; or alkyl, cycloalkyl, aryl or heteroaryl, each of which is optionally substituted. The present invention also relates to the discovery that compounds having Formula (V) are activators of caspases and inducers of apoptosis. Therefore, the compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

L'invention porte sur des nicotinamides substituées et leurs analogues de formule (V) ou un de leurs sels pharmacocompatibles ou précurseur, dans laquelle: Ar' et Ar sont indépendamment aryle facultativement substitué, ou hétéroaryle facultativement substitué, sous réserve que la structure cyclique dudit hétéroaryle facultativement substitué ne comporte pas plus de deux atomes d'azote; et R¿11? est hydrogène; ou alkyle, cycloalkyle, aryle ou hétéroaryle, tous étant facultativement substitués. L'invention porte également sur la découverte selon laquelle lesdits composés de formule (V) sont des activateurs des caspases et des inducteurs d'apoptose. C'est pourquoi, on peut les utiliser pour provoquer la mort cellulaire dans une variété de conditions cliniques où se produit la croissance non contrôlée et la diffusion de cellules anormales.

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