| 19640711 |
Chen Z, Venkatesan AM, Dehnhardt CM, Dos Santos O, Delos Santos E, Ayral-Kaloustian S, Chen L, Geng Y, Arndt KT, Lucas J, Chaudhary I, Mansour TS: 2,4-Diamino-quinazolines as inhibitors of beta-catenin/Tcf-4 pathway: Potential treatment for colorectal cancer. Bioorg Med Chem Lett. 2009 Sep 1;19(17):4980-3. Epub 2009 Jul 17.
The synthesis and SAR of a series of 2,4-diamino-quinazoline derivatives as beta-catenin/Tcf-4 inhibitors are described. This series was developed by modifying the initial lead 1, which was identified by screening of our compound library and found to inhibit the beta-catenin/Tcf-4 pathway. Replacement of the biphenyl moiety in compound 1 with the N-phenylpiperidine-4-carboxamide chain as in 2, resulted in a number of new analogues, which are potent inhibitors of the beta-catenin/Tcf-4 pathway. Compound such as 16k exhibited good cellular potency, solubility, metabolic stability and oral bioavailability. |
84(1,1,1,4) |