Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1363684 | Bioorganic & Medicinal Chemistry Letters | 2009 | 4 Pages |
The synthesis and SAR of a series of 2,4-diamino-quinazoline derivatives as β-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 β-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 β-catenin/Tcf-4 pathway. Compound such as 16k exhibited good cellular potency, solubility, metabolic stability and oral bioavailability.
Graphical abstractThe synthesis and SAR of a series of 2,4-diamino-quinazoline derivatives as β-catenin/Tcf-4 inhibitors are described.Figure optionsDownload full-size imageDownload as PowerPoint slide