title: Development of 3D-QSAR CoMSIA models for 5-(biphenyl-2-yl)-1H-tetrazole derivatives as angiotensin II receptor type 1 (AT1) antagonists.
abstract: As a development strategy for backups of Fimasartan (1), a comparative molecular similarity indices analysis (CoMSIA) of a set of sixty-five 5-(biphenyl-2-yl)-1H-tetrazole derivatives has been performed to find out the pharmacophore elements for angiotensin II receptor type 1 (AT1) blockade. The most potent compound containing pyrimidin-4(3H)-one ring, Fimasartan (1) was used to align the molecules. As a result, we obtained 3D-QSAR model which provided good predictivity for both the training set (q(2)=0.846, r(2)=0.975) and the external test set (rpred(2)=0.980). This model would guide the design of backups for Fimasartan (1), a launched oral antihypertensive agent.
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Gi Hyun
authors.initials: GH
authors.lastname: Kwon
authors.forename: Nam Seok
authors.initials: NS
authors.lastname: Han
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Yoo
authors.forename: Je Hak
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo Heui
authors.initials: SH
authors.lastname: Paik
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Chi
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
mesh_terms: D057912:Angiotensin II Type 2 Receptor Blockers / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D003198:Computer Simulation; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D011743:Pyrimidines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; C010574:biphenyl; C558933:fimasartan
keywords: 3D-QSAR; Angiotensin II receptor type 1 (AT(1)); Antagonist; Antihypertensive agent; CoMSIA; Pyrimidin-4(3H)-one