Abstract:
:The tyrosine kinase inhibitory action of the derivatives of N-Phenyl-N'-{4-(4-quinolyloxy)phenyl}urea is quantitatively analyzed using multiple regression analysis. The analysis has helped to ascertain the role of different substituents in explaining the observed inhibitory actions of these compounds for two receptors, namely vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor receptor alpha (PDGFRalpha). From a derived significant correlation equation for inhibition of VEGFR-2, it was concluded that a less hydrophobic molecule with ortho-substituent(s), exerting less steric hindrance and para-substituent devoid of hydrogen-bond acceptor property augment the inhibition action. Besides, a 3-substituent transmitting a higher negative field effect is advantageous to improve the pIC(50) value of a compound. The correlation equation, derived for the inhibition of PDGFRalpha, has revealed that a less hydrophobic molecule, having a 3-substituent which transmits a more negative resonance effect, is helpful in raising its activity. Likewise, in the middle phenyl ring, absence of a fluoro substituent augments the inhibitory activity. Based on derived QSAR equations pertaining to VEGF-2 and PDGFalpha receptors, the drawn guidelines for selection of substituents, may be used to synthesize potent compounds in future.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Sharma BK,Sharma SK,Singh P,Sharma Sdoi
10.1080/14756360701450301subject
Has Abstractpub_date
2008-04-01 00:00:00pages
168-73issue
2eissn
1475-6366issn
1475-6374pii
779687351journal_volume
23pub_type
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