QSAR studies of imidazo (1,5-<i style=""><img src='/image/spc_char/alpha.gif' border=0> </i>) quinoxalines amides, carbamates and ureas as potent GABA modulators

Abstract

Quantitative structure activity relationship (QSAR) studies have been performed on imidazo(1,5-<i style=""><img src='/image/spc_char/alpha.gif' border=0> </i>)quinoxalines amides, carbamates and ureas. The QSAR models have been developed by using multiple linear regression in order to identify descriptors, which are actually focusing towards the biological activity. Leave out-group of rows method, usually employed in cross validation analysis, are used to validate the developed model. The best predictive QSAR model derived, had r²cv of 0.81, non-cross validated r² of 0.87, predictive r²for test set 0.61 and standard error of estimate 0.23. The model reveals that multidimensional steric [verloop B₅ (subs 4)], hydrophobic [Log P (whole molecule)], electro topological [Ipso atom E state index (subs 2) and sum of E state indices (subs 4)] and hydrogen bond donor [ADME H bond donor (subs 4)] descriptors have significant impact on GABA modulator activity of the compounds. The results clearly indicate the soundness and predictive ability of the model. Using this model novel anxiolytics and anticonvulsants can be obtained with improved potency and pharmacokinetic profile.