title: Molecular modeling studies on 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1 receptor.
abstract: A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed on a series of the 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1 receptor. The CoMFA and CoMSIA models resulting from a 21 molecule training set gave r²(cv) values of 0.631 and 0.542 and r² values of 0.986 and 0.981, respectively. The statistically significant models were validated by a test set of five compounds with predictive r²(pred). values of 0.967 and 0.981 for CoMFA and CoMSIA, respectively. A systemic external validation was also performed on the established models. The information obtained from 3D counter maps could facilitate the design of more potent human TRPA1 receptor agonists.
authors.affiliation: College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ai
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Song
authors.forename: Shao-Teng
authors.initials: ST
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
mesh_terms: D001381:Azepines / Q000737:chemistry*; D015220:Calcium Channels / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000737:chemistry*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000737:chemistry*
chemical_list: D001381:Azepines; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels