title: Discovery of novel non-steroidal reverse indole mineralocorticoid receptor antagonists.
abstract: 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.
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Ogawa
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Ellen Vande
authors.initials: EV
authors.lastname: Bunte
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Rudrajit
authors.initials: R
authors.lastname: Mal
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Judyann
authors.initials: J
authors.lastname: Wiltsie
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Clemas
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Contino
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: JeanMarie
authors.initials: J
authors.lastname: Lisnock
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Garcia-Calvo
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Jochnowitz
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Ma
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brown
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Zamlynny
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bateman
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Leung
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Crook
authors.affiliation: Early Development and Discovery Sciences, Merck and Co., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sinclair
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid
keywords: Eplerenone; Hypertension; Mineralocorticoid receptor antagonist; Spironolactone