title: Design, synthesis, and bioactivity of pyrazole acid derivatives as endothelin receptor antagonists.
abstract: A series of novel pyrazole carboxylic acid derivatives was designed and synthesized, and their antagonism effect on endothelin (ET)-1-induced contraction in the rat thoracic aortic ring was screened. The radio receptor assay was used to examine the potency of the compounds on ET receptor. Some target compounds demonstrated significant inhibitory activity, especially 7m, which showed a potent inhibition percentage higher than the contrast compound BQ123. Further assays on the binding and selectivity for ET showed that 7m had highly potent binding activity on ETA at the nanomole level, and the ratio of ETA/ETB was 36. Therefore, we inferred that 7m was a non-selective antagonist of ETA and ETB and had potential for further development in cardiovascular diseases.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing 210009, Jiangsu, China. jimin@seu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.forename: Ligang
authors.initials: L
authors.lastname: Liu
authors.forename: Junqing
authors.initials: J
authors.lastname: Chen
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Ji
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011720:Pyrazoles; C031280:pyrazole