title: Mineralocorticoid receptor antagonists: identification of heterocyclic amide replacements in the oxazolidinedione series.
abstract: Novel potent and selective mineralocorticoid receptor antagonists were identified, utilizing heterocyclic amide replacements in the oxazolidinedione series. Structure-activity relationship (SAR) efforts focused on improving lipophilic ligand efficiency (LLE) while maintaining nuclear hormone receptor selectivity and reasonable pharmacokinetic profiles.
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: jason_cox@merck.com.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cox
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Hong D
authors.initials: HD
authors.lastname: Chu
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Hong C
authors.initials: HC
authors.lastname: Shen
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Jaume
authors.initials: J
authors.lastname: Balsells
authors.affiliation: Department of Chemistry Modeling & Informatics, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
authors.affiliation: Department of Cardiovascular Diseases, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brown
authors.affiliation: Department of Cardiovascular Diseases, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Zamlynny
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Judyann
authors.initials: J
authors.lastname: Wiltsie
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Clemas
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Contino
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: JeanMarie
authors.initials: J
authors.lastname: Lisnock
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Garcia-Calvo
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bateman
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.affiliation: Department of Cardiovascular Diseases, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Crook
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sinclair
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008862:Microsomes, Liver; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D006571:Heterocyclic Compounds; D000451:Mineralocorticoid Receptor Antagonists; D010080:Oxazoles; D018161:Receptors, Mineralocorticoid
keywords: Hypertension; Lipophilic ligand efficiency; Mineralocorticoid receptor antagonist; Oxazolidinedione