title: Synthesis and in vitro evaluation of ambrisentan analogues as potential endothelin receptor antagonists.
abstract: A series of novel 2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3,3-diphenyl butyric acid derivatives were synthesized and evaluated for their antagonistic activity for endothelin-1-induced contraction in rabbit aorta. Within this series of compounds, 2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-cyano-3,3-diphenylpropionic acid (4) displays comparable potency with ambrisentan (1), and warrants further investigation.
authors.affiliation: Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Jianfei
authors.initials: J
authors.lastname: Song
authors.forename: Le
authors.initials: L
authors.lastname: Zhen
authors.forename: Xiuling
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiantao
authors.initials: X
authors.lastname: Lei
authors.forename: Lina
authors.initials: L
authors.lastname: Zheng
authors.forename: Qiujuan
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D015394:Molecular Structure; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: C562360:2-((4,6-dimethylpyrimidin-2-yl)oxy)-3-cyano-3,3-diphenylpropionic acid; D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D011743:Pyrimidines; C467894:ambrisentan