Quantitative Structure Activity Relationship between Diazabicyclo- (4.2.0)octanes Derivatives and Nicotinic Acetylcholine Receptor Agonists

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor (hα4β2 and hα3β4) agonists was studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models (q2=0.926 and 0.945, r2ncv=0.983 and 0.988). This study can be used to develop potent hα4β2 receptor agonists with low activity on hα3β4 subtype.