title: Discovery of novel oxazolidinedione derivatives as potent and selective mineralocorticoid receptor antagonists.
abstract: Novel oxazolidinedione analogs were discovered as potent and selective mineralocorticoid receptor (MR) antagonists. Structure-activity relationship (SAR) studies were focused on improving the potency and microsomal stability. Selected compounds demonstrated excellent MR activity, reasonable nuclear hormone receptor selectivity, and acceptable rat pharmacokinetics.
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. christine_yang@merck.com
authors.forename: Christine
authors.initials: C
authors.lastname: Yang
authors.forename: Hong C
authors.initials: HC
authors.lastname: Shen
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Wu
authors.forename: Hong D
authors.initials: HD
authors.lastname: Chu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cox
authors.forename: Jaume
authors.initials: J
authors.lastname: Balsells
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
authors.forename: Patricia
authors.initials: P
authors.lastname: Brown
authors.forename: Beata
authors.initials: B
authors.lastname: Zamlynny
authors.forename: Judyann
authors.initials: J
authors.lastname: Wiltsie
authors.forename: Joseph
authors.initials: J
authors.lastname: Clemas
authors.forename: Jack
authors.initials: J
authors.lastname: Gibson
authors.forename: Lisa
authors.initials: L
authors.lastname: Contino
authors.forename: Jeanmarie
authors.initials: J
authors.lastname: Lisnock
authors.forename: Gaochao
authors.initials: G
authors.lastname: Zhou
authors.forename: Margarita
authors.initials: M
authors.lastname: Garcia-Calvo
authors.forename: Tom
authors.initials: T
authors.lastname: Bateman
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Martin
authors.initials: M
authors.lastname: Crook
authors.forename: Peter
authors.initials: P
authors.lastname: Sinclair
mesh_terms: D000818:Animals; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D062105:Molecular Docking Simulation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D017434:Protein Structure, Tertiary; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010080:Oxazoles; D018161:Receptors, Mineralocorticoid; C064210:oxazolidine