title: Probing the structural and topological requirements for CCR2 antagonism: holographic QSAR for indolopiperidine derivatives.
abstract: CCR2 is the major family of chemokine receptors which involve in the pathophysiology of the acute or chronic inflammatory conditions such as rheumatoid arthritis, atherosclerosis, asthma, obesity, and type-2 diabetes. Herein, we report the results of HQSAR model, developed for CCR2 antagonistic activity of indolopiperidine derivatives. The best HQSAR model with r(2)=0.916, q(2)=0.562 with atom count=4-7 was used to predict the activity of the test set molecules. The predicted values are in good agreement with experimental results and show the potential of the model for untested compounds. Analysis of molecular fragments throws light on essential structural and topological features of indolopiperidine derivatives for antagonist activity. The analysis shows that the presence of tertiary hydrogen bond acceptor groups is important for CCR2 antagonism. Fragments containing benzene ring substituted with one or more chlorine atoms show the positive effect of electron withdrawing group for favorable activity.
authors.affiliation: Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: K
authors.initials: K
authors.lastname: Srikanth
authors.forename: Pramod C
authors.initials: PC
authors.lastname: Nair
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
mesh_terms: D006696:Holography / Q000379:methods; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D007211:Indoles; D010880:Piperidines; D054390:Receptors, CCR2; C435666:indolopiperidine