19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension. Issue 19 (1st October 2019)

• Record Type: Journal Article
• Authors: Dakarapu, Rambabu; Errabelli, Ramu; Manthati, Vijaya L.; Michael Adebesin, Adeniyi; Barma, Deb K.; Barma, Deepan; Garcia, Victor; Zhang, Fan; Laniado Schwartzman, Michal; Falck, John R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 19(2019)
• Publication Date: 2019-10-01
• Subjects: QDEGARKRKXEQDF-AAHZGTINSA-M; Antagonist -- Vascular sensitization -- Hypertension -- Eicosanoid -- Bioisosteric replacement; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.08.020
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 19-Hydroxyeicosatetraenoic acid (19-HETE, 1 ), a metabolically and chemically labile cytochrome P450 eicosanoid, has diverse biological activities including antagonism of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE, 2 ). A SAR study was conducted to develop robust analogs of 1 with improved in vitro and in vivo efficacy. Analogs were screened in vitro for inhibition of 20-HETE-induced sensitization of rat renal preglomerular microvessels toward phenylephrine and demonstrated to normalize the blood pressure of male Cyp4a14(-/-) mice that display androgen-driven, 20-HETE-dependent hypertension.