Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity. Issue 4 (15th February 2015)

• Record Type: Journal Article
• Authors: Cai, Jin; Liu, Ligang; Hong, Kwon Ho; Wang, Peng; Li, Lushen; Cao, Meng; Sun, Chunlong; Wu, Xiaoqing; Zong, Xi; Chen, Junqing; Ji, Min
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 4(2015)
• Page Start: 657
• Page End: 667
• Publication Date: 2015-02-15
• Subjects: Endothelin -- Phenoxybutanoic acid -- PAH -- SAR -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.01.003
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that6e and6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compoundBQ123 . The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that6e was a selective ETA antagonist with a nanomolar IC50 . Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases.