Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation.
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.
Zhao
Hongyu
H
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. hongyu.zhao@abbott.com
Xin
Zhili
Z
Liu
Gang
G
Schaefer
Verlyn G
VG
Falls
H Douglas
HD
Kaszubska
Wiweka
W
Collins
Christine A
CA
Sham
Hing L
HL
D015195:Drug Design; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D054440:Receptors, Ghrelin; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013764:Tetrahydronaphthalenes; C095210:tetralin