COMPARATIVE QSAR STUDY ON ALKYL AND ALKOXY SUBSTITUTED 1, 4 DIHYDROQUINOXALINE-2, 3-DIONES AND 5-(N-OXYAZA)-7-SUBSTITUTED-1, 4-DIHYDROQUINOXALINE-2, 3-DIONES AS GLYCINE/NMDA SITE ANTAGONISTS

Dr. Neelam Khan* and Dr. Manish Sharma

ABSTRACT

In this article demonstrated for glycine site, the inhibition potency was found to be well correlated linearly with lipophilicity  and Hammett constant  parameters of substituent. The models were internally (Q2) and externally (Q2ext) validated and all the statistical parameters met with like leave-one-out cross-validation, an external test set and Y-randomization test. Applicability domain was verified by the standardization approach. Similarly it was also found that any substitution other than CH3 and Cl at R6 will prove to be unfruitful for receptor inhibition. It suggests that there exists a linear relationship with positive slope between  /m and enzyme inhibition, i.e., increasing the value of  and  will increase the potency of the compounds. The coefficient of  is 1.11, which is well between the optimum range of 0.4-1.4. A positive coefficient for  indicates that lipophilic substituents are favorable for inhibiting the receptor. Simultaneously, the substituents should be electron withdrawing also, which is indicated by the positive sign of  coefficient.

Keywords: QSAR, Glycine, NMDA.