898282-74-1Relevant academic research and scientific papers
Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration
Sirisoma, Nilantha,Pervin, Azra,Zhang, Hong,Jiang, Songchun,Willardsen, J. Adam,Anderson, Mark B.,Mather, Gary,Pleiman, Christopher M.,Kasibhatla, Shailaja,Tseng, Ben,Drewe, John,Cai, Sui Xiong
experimental part, p. 2341 - 2351 (2010/03/31)
As a continuation of our structure-activity relationship (SAR) studies on 4-anilinoquinazolines as potent apoptosis inducers and to identify anticancer development candidates, we explored the replacement of the 2-Cl group in our lead compound 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (6b, EP128265, MPI-0441138) by other functional groups. This SAR study and lead optimization resulted in the identification of N-(4-methoxyphenyl)-N,2- dimethylquinazolin-4-amine (6h, EP128495, MPC-6827) as an anticancer clinical candidate. Compound 6h was found to be a potent apoptosis inducer with EC 50 of 2 nM in our cell-based apoptosis induction assay. It also has excellent blood brain barrier penetration, and is highly efficacious in human MX-1 breast and other mouse xenograft cancer models.
COMPOUNDS AND THERAPEUTICAL USE THEREOF
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Page/Page column 76, (2008/06/13)
Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
