title: Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation.
abstract: A case study of rational design of an efficient, specific, and proprietary molecular scaffold based on the structure-activity relationship (SAR) information on a screening hit is described. Potent, selective, and orally bioavailable tetralin carboxamide growth hormone secretagogue receptor (GHS-R) antagonists were discovered. Union of rational design and high throughput synthesis provided a quick access to high quality chemical leads.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. hongyu.zhao@abbott.com
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
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: D015195:Drug Design; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D054440:Receptors, Ghrelin; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013764:Tetrahydronaphthalenes; C095210:tetralin