Quantitative Structure Activity Relationship between Diazabicyclo4.2.0octanes Derivatives and Nicotinic Acetylcholine Receptor Agonists

ABSTRACT

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor (h alpha4beta2 and h alpha3beta4) 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, r2(ncv)=0.983 and 0.988). This study can be used to develop potent h alpha4beta2 receptor agonists with low activity on h alpha3beta4 subtype.