Design and synthesis of novel diaminoquinazolines with in vivo efficacy for β-catenin/T-cell transcriptional factor 4 pathway inhibition

…, S Ayral-Kaloustian, O Dos Santos…

文献索引：Dehnhardt, Christoph M.; Venkatesan, Aranapakam M.; Chen, Zecheng; Ayral-Kaloustian, Semiramis; Dos Santos, Osvaldo Dos; Delos Santos, Efren; Curran, Kevin; Follettie, Max T.; Diesl, Veronica; Lucas, Judy; Geng, Yi; DeJoy, Susan Quinn; Petersen, Rosanne; Chaudhary, Inder; Brooijmans, Natasja; Mansour, Tarek S.; Arndt, Kim; Chen, Lei Journal of Medicinal Chemistry, 2010 , vol. 53, # 2 p. 897 - 910

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被引用次数: 22

摘要

We are introducing a novel series of 2, 4-diaminoquinazolines as β-catenin/Tcf4 inhibitors which were identified by ligand-based design. Here we elucidate the SAR of this series and explain how we were able to improve key molecular properties such as solubility and cLogP leading to compound 9. Analogue 9 exhibited better biological activity and improved physical and pharmacological properties relative to the HTS hit 49. Furthermore, 9 ...