2. Academic Validation
  3. Novel 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety as angiokinase inhibitors

Novel 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety as angiokinase inhibitors

  • Bioorg Med Chem. 2017 Mar 15;25(6):1778-1786. doi: 10.1016/j.bmc.2017.01.039.
Mingze Qin 1,  Shuang Yan 2,  Lei Wang 2,  Haotian Zhang 3,  Ye Tian 2,  Yanfang Zhao 2,  Ping Gong 4
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. Electronic address: qinmingze001@126.com.
  • 2 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China.
  • 3 Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
  • 4 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: 28190652 DOI: 10.1016/j.bmc.2017.01.039
Abstract

Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing Apoptosis. Compound 8a has emerged as a promising lead compound for development of angiokinase inhibitors targeting VEGFR and PDGFR.

Keywords

6-Methoxycarbonyl indolinones; Angiokinase inhibitors; Antitumor activity; Conformational restriction strategy.

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