Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors

Title
Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors
Authors
니아즈파샤M. Muddassar이소하심태보하정미조승주
Keywords
CoMFA; CoMSIA; drug design; pharmacophore; VEGFR; 3D-QSAR; 2E20060삭제후위계정추가요청('091019,Dr이소하)
Issue Date
2009-03
Publisher
Medicinal chemistry research
Citation
VOL 18, NO 2, 127-142
Abstract
The growth and metastasis of solid tumors are dependent on angiogenesis. The vascular endothelial growth factor (VEGF) is of particular interest since it is essential for angiogenesis. The development of novel inhibitors of VEGF receptor type 2 (VEGFR-2) is important. Quantitative structure–activity relationship (QSAR) studies were performed to understand the structural factors affecting inhibitory potency of 4-aryl-5-cyano-2-aminopyrimidines. Pharmacophore models indicate that the importance of steric and hydrogen bond acceptor groups. The bestfitted pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Both CoMFA (q2 = 0.62, r2 = 0.87, and r2 predictive = 0.7) and CoMSIA (q2 = 0.54, r2 = 0.86, and r2 predictive = 0.61) gave reasonable results. Factors such as steric bulkiness, electrostatic effect, and hydrogen bond acceptor were found to be important for the inhibitory activity. It is suggested that negatively charged, bulky H-bond accepting groups around the piperazine nitrogen would enhance inhibition against VEGFR-2.
URI
http://pubs.kist.re.kr/handle/201004/33539
ISSN
1054-2523
Appears in Collections:
KIST Publication > Article
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