title: Exploring selectivity requirements for COX-2 versus COX-1 binding of 3,4-diaryloxazolones using E-state index.
abstract: Considering the importance of developing selective COX-2 inhibitors, the present paper explores selectivity requirements for COX-2 versus COX-1 binding of 3,4-diaryloxazolones using electrotopological state (E-state) index. The study also shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance: electron density distribution of different atoms of the oxazolone ring and attached two phenyl rings are important for the selective binding with COX-2 over COX-1. Moreover, the use of indicator variable shows that presence of ortho R(1) substituent (except fluoro) on the N(3)-phenyl ring decreases COX-2 selectivity. Further, an amino substituent at R(2) position (i.e., sulfonamide compound) is favorable for increasing COX-2 selectivity when the R(3) position is unsubstituted.
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India. kunalroy_in@yahoo.com
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
authors.forename: Santanu
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Achintya
authors.initials: A
authors.lastname: Saha
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007527:Isoenzymes / Q000737:chemistry / Q000187:drug effects*; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010081:Oxazolone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases