title: Novel isoxazole carboxamides as growth hormone secretagogue receptor (GHS-R) antagonists.
abstract: Novel isoxazole carboxamides have been identified as growth hormone secretagogue receptor (GHS-R) antagonists. Substituent modification off the 5-position of the isoxazole ring led to analogues with potent binding affinity and functional antagonism of GHS-R. A potent analogue (32) with high aqueous solubility and good GPCR selectivity was also identified as a potential pharmacological tool for in vivo studies.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Micheal D
authors.initials: MD
authors.lastname: Serby
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Verlyn G
authors.initials: VG
authors.lastname: Schaefer
authors.forename: H Douglas
authors.initials: HD
authors.lastname: Falls
authors.forename: Wiweka
authors.initials: W
authors.lastname: Kaszubska
authors.forename: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011869:Radioligand Assay; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D054440:Receptors, Ghrelin; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D000577:Amides; D007555:Isoxazoles; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D014867:Water