Discovery of novel non-steroidal reverse indole mineralocorticoid receptor antagonists.

Autor: Ogawa AK; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Bunte EV; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Mal R; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Lan P; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Sun Z; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Crespo A; Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA., Wiltsie J; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Clemas J; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Gibson J; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Contino L; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Lisnock J; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Zhou G; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Garcia-Calvo M; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Jochnowitz N; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Ma X; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Pan Y; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Brown P; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Zamlynny B; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Bateman T; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Leung D; Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA., Xu L; Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA., Tong X; Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA., Liu K; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Crook M; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA., Sinclair P; Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Jun 15; Vol. 26 (12), pp. 2866-2869. Date of Electronic Publication: 2016 Apr 20.
DOI: 10.1016/j.bmcl.2016.04.052
Abstrakt: Reported herein are a series of reverse indoles that represent novel non-steroidal mineralocorticoid receptor (MR) antagonists. The key structure-activity relationships (SAR) are presented below. This reverse indole series is exemplified by a compound that demonstrated efficacy in an acute natriuresis rodent model comparable to marketed MR antagonists, spironolactone and eplerenone.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: