47 0

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

Title
Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors
Author
하정미
Keywords
CoMFA; CoMSIA; Drug design; Pharmacophore; VEGFR; 3D-QSAR
Issue Date
2009-08
Publisher
BIRKHAUSER BOSTON INC
Citation
MEDICINAL CHEMISTRY RESEARCH, v. 18, No. 2, Page. 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 best-fitted pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Both CoMFA (q(2) = 0.62, r(2) = 0.87, and r(predictive)(2) = 0.7) and CoMSIA (q(2) = 0.54, r(2) = 0.86, and r(predictive)(2) = 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
https://link.springer.com/article/10.1007/s00044-008-9113-4http://repository.hanyang.ac.kr/handle/20.500.11754/76239
ISSN
1054-2523
DOI
10.1007/s00044-008-9113-4
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE