Novel isoxazole carboxamides as growth hormone secretagogue receptor (GHS-R) antagonists.
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.
Liu
Bo
B
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA.
Liu
Gang
G
Xin
Zhili
Z
Serby
Micheal D
MD
Zhao
Hongyu
H
Schaefer
Verlyn G
VG
Falls
H Douglas
HD
Kaszubska
Wiweka
W
Collins
Christine A
CA
Sham
Hing L
HL
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
D000577:Amides; D007555:Isoxazoles; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D014867:Water