Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors
- Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors
- 니아즈; 파샤; M. Muddassar; 이소하; 심태보; 하정미; 조승주
- CoMFA; CoMSIA; drug design; pharmacophore; VEGFR; 3D-QSAR; 2E20060삭제후위계정추가요청('091019,Dr이소하)
- Issue Date
- Medicinal chemistry research
- VOL 18, NO 2, 127-142
- 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.
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