Cbi analogues of cc-1065 and the duocarmycins

Details Cbi analogues of cc-1065 and the duocarmycins Cbi analogues of cc-1065 and the duocarmycins

C - Chemistry, Metallurgy

07

D

C07D 417/14 (2006.01) A61K 31/403 (2006.01) A61K 31/404 (2006.01) A61K 31/4178 (2006.01) A61K 31/4184 (2006.01) A61K 31/423 (2006.01) A61K 31/427 (2006.01) A61P 35/00 (2006.01) C07D 209/56 (2006.01) C07D 209/60 (2006.01) C07D 403/12 (2006.01) C07D 403/14 (2006.01) C07D 405/12 (2006.01) C07D 405/14 (2006.01) C07D 409/12 (2006.01) C07D 409/14 (2006.01) C07D 413/12 (2006.01) C07D 413/14 (2006.01) C07D 417/12 (2006.01) C07D 487/04 (2006.01) C07D 487/10 (2006.01) C07D 519/00 (2006.01)

Patent

CA 2459308

132 CBI analogues of CC-1 065 and the duocarmycins having dimeric monocyclic, bicyclic, and tricyclic heteroaromatics substituents were synthesized by a parallel route. The resultant analogues were evaluated with respect to their catalytic and cytotoxic activities. The relative contribution of the various dimeric monocyclic, bicyclic, and tricyclic heteroaromatics substituents within the DNA binding domain were characterized. Several of the resultant CBI analogues of CC-1065 and the duocarmycins were characterized as having enhanced catalytic and cytotoxic activities and were identified as having utility as anti-cancer agents.

Selon l'invention, 132 analogues CBI de CC-1065 et des duocarmycines comportant des substituants monocycliques, bicycliques, et tricycliques hétéroaromatiques dimères, ont été synthétisés par une voie parallèle. Ces analogues ont été évalués par rapport à leurs activités catalytique et cytotoxique. La contribution relative des différents substituants monocycliques, bicycliques, et tricycliques hétéroaromatiques dimères au domaine de liaison d'ADN a été caractérisée. Plusieurs des analogues CBI de CC-1065 et des duocarmycines ont été caractérisés comme possédant des activités catalytique et cytotoxique améliorées et ont été identifiés en tant qu'anticancéreux utiles.

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