title: CoMFA and CoMSIA analyses on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine derivatives as selective CB2 receptor agonists.
abstract: Novel classes of CB2 agonists based on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine scaffolds have shown high binding affinity toward CB2 receptor and good selectivity over CB1. A computational study of comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed, in order to identify the key structural features impacting their binding affinity. The final CoMSIA model resulted to be the more predictive, showing r(2)ncv=0.84, r(2)cv=0.619, SEE = 0.369, and r(2)pred=0.75. The study provides useful suggestions for the synthesis of new selective analogues with improved affinity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, 16132, Genova, Italy. cichero@unige.it
authors.forename: Elena
authors.initials: E
authors.lastname: Cichero
authors.forename: Sara
authors.initials: S
authors.lastname: Cesarini
authors.forename: Luisa
authors.initials: L
authors.lastname: Mosti
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
mesh_terms: D006801:Humans; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*
chemical_list: D009287:Naphthyridines; D011804:Quinolines; D043885:Receptor, Cannabinoid, CB2