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Phenyl and Diaryl Ureas with Thiazolo[5,4‐ d ]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation
Author(s) -
Xue WenJun,
Deng YaHui,
Yan ZhongHui,
Liu JiPing,
Liu Yu,
Sun LiPing
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201800493
Subject(s) - angiogenesis , umbilical vein , chemistry , in vitro , pyrimidine , angiogenesis inhibitor , pharmacology , stereochemistry , cancer research , biochemistry , biology
Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor‐2 (VEGFR‐2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4‐ d ]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1‐(4‐Fluorophenyl)‐3‐{4‐[(5‐methyl‐2‐phenyl[1,3]thiazolo[5,4‐ d ]pyrimidin‐7‐yl)amino]phenyl}urea ( 19b ) and 1‐(3‐Fluorophenyl)‐3‐{4‐[(5‐methyl‐2‐phenyl[1,3]thiazolo[5,4‐ d ]pyrimidin‐7‐yl)amino]phenyl}urea ( 19g ) exhibited the most potent inhibitory effect on HUVEC proliferation (IC 50 =12.8 and 5.3 μ m , respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.