title: Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates.
abstract: A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50=0.4 nM) and 15e (IC50=5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Organic Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Shengtao
authors.initials: S
authors.lastname: Xu
authors.forename: Hengyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Renren
authors.initials: R
authors.lastname: Bai
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Jieyun
authors.initials: J
authors.lastname: Jiang
authors.forename: Mingqin
authors.initials: M
authors.lastname: Shen
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D044139:Receptor, Angiotensin, Type 2; D013449:Sulfonamides; D014230:Triazoles; C045575:1,2,4-triazole
keywords: AT(2) receptor; Agonists; Antihypertensive activity; Biphenyl-2-sulfonamide derivatives; Structure–activity relationships