19-Hydroxyeicosatetraenoic Acid Analogs: Antagonism of 20-Hydroxyeicosatetraenoic Acid-Induced Vascular Sensitization and Hypertension
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.
Dakarapu, R., Errabelli, R., Manthati, V., Michael Adebesin, A., Barma, D., Barma, D., Garcia, V., Zhang, F., Laniado Schwartzman, M., & Falck, J. (2019). 19-Hydroxyeicosatetraenoic Acid Analogs: Antagonism of 20-Hydroxyeicosatetraenoic Acid-Induced Vascular Sensitization and Hypertension. Bioorganic & Medicinal Chemistry Letters, 29 (19), 126616. https://doi.org/10.1016/j.bmcl.2019.08.020