Novel 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety as angiokinase inhibitors. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Qin, Mingze; Yan, Shuang; Wang, Lei; Zhang, Haotian; Tian, Ye; Zhao, Yanfang; Gong, Ping
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 6(2017)
• Page Start: 1778
• Page End: 1786
• Publication Date: 2017-03-15
• Subjects: 6-Methoxycarbonyl indolinones -- Conformational restriction strategy -- Angiokinase inhibitors -- Antitumor activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.01.039
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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. Compound8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis. Compound8a has emerged as a promising lead compound for development of angiokinase inhibitors targeting VEGFR and PDGFR.