Design and synthesis of novel tubulin polymerization...

C - Chemistry – Metallurgy – 07 – D

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C07D 239/38 (2006.01) A61K 31/38 (2006.01) A61K 31/404 (2006.01) A61K 31/4152 (2006.01) A61K 31/427 (2006.01) A61K 31/428 (2006.01) A61K 31/505 (2006.01) A61P 35/00 (2006.01) C07D 209/04 (2006.01) C07D 213/70 (2006.01) C07D 237/18 (2006.01) C07D 279/06 (2006.01) C07D 279/08 (2006.01) C07D 307/78 (2006.01)

Patent

CA 2606174

A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to compound 1, against cancer cell lines. 6n was more effective than compound 1 in causing apoptosis of MCF- 7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC50 of 2.1 ~M.

L'invention porte sur une nouvelle série d'analogues de la BPU qui ont été synthétisés et évalués pour l'activité antitumorale. Notamment, les analogues de souffre de la BPU 6n et 7d s'avèrent posséder une puissance accrue de dix fois, comparé à un composé 1, contre les lignées cellulaires cancéreuses. 6n s'est avéré plus efficace que le composé 1 dans la génération de l'apoptose des cellules MCF-7. Lorsqu'il est comparé à d'autres médicaments ayant un mécanisme d'action similaire, 6n a conservé une capacité considérable à inhiber l'ensemble tubuline, avec un IC50 de 2,1 ?M.

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