1. Academic Validation
  2. Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 1

Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 1

  • Bioorg Med Chem. 2013 Jun 1;21(11):2879-85. doi: 10.1016/j.bmc.2013.03.061.
Weisi Wang 1 Shihao Shangguan Ni Qiu Chunqi Hu Lei Zhang Yongzhou Hu
Affiliations

Affiliation

  • 1 ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Abstract

A series of 3,4,5-trisubstituted aminothiophenes were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory potency and anti-proliferation activities against A549 and PC3 tumor cell lines. Fourteen compounds had appreciably improved MDM2 binding affinities than lead compound MCL0527 (3) and a few compounds showed comparable activities to that of Nutlin-3. Meanwhile, most of the 3,4,5-trisubstituted aminothiophenes displayed better or equivalent anti-proliferation activities against wild-type p53 cell line A549 compared to that of Nutlin-3. Over ten compounds exhibited desirable selective profiles of p53 status. Particularly, compounds 9, 16 and 18 displayed 22-, 6- and 22-fold selectivity of p53 status, respectively, much better than that of Nutlin-3 (fourfold).

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