2. Academic Validation
  3. Discovery of novel diaryl urea derivatives bearing a triazole moiety as potential antitumor agents

Discovery of novel diaryl urea derivatives bearing a triazole moiety as potential antitumor agents

  • Eur J Med Chem. 2016 Jun 10:115:1-13. doi: 10.1016/j.ejmech.2016.02.071.
Mingze Qin 1,  Shuang Yan 1,  Lei Wang 1,  Haotian Zhang 2,  Yanfang Zhao 1,  Shasha Wu 1,  Di Wu 1,  Ping Gong 3
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: gongpinggp@126.com.
PMID: 26991938 DOI: 10.1016/j.ejmech.2016.02.071
Abstract

Herein, we report a novel series of diaryl urea derivatives bearing a triazole moiety, from which potent antitumor agents have been identified. With a modified triazole, most compounds showed high level activity in both cellular and enzymatic assays, accompanied with a suitable ClogD7.4 value. The most active compound, 13i, effectively suppressed proliferation of HT-29, H460 and MDA-MB-231 Cancer cells, with IC50 values of 0.90, 0.85 and 1.54 μM, respectively. Compound 13i also exhibited significant inhibition of tyrosine kinases including c-Kit, RET and FLT3. Furthermore, compound 13i could obviously induce Apoptosis of HT-29 cells in a concentration-dependent manner. The study of structure-activity relationships also revealed that a hydrophilic tail at the 4-position of the triazole was crucial for high activity of the compound.

Keywords

Antitumor activity; Diaryl ureas; Organic synthesis; Structure-activity relationship.

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