Potent achiral agonists of the ghrelin (growth hormone secretagogue) receptor. Part I: Lead identification

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 23; pp. 6584 - 6587
• Main Authors: Heightman, Tom D., Scott, Jackie S., Longley, Mark, Bordas, Vincent, Dean, David K., Elliott, Richard, Hutley, Gail, Witherington, Jason, Abberley, Lee, Passingham, Barry, Berlanga, Manuela, de los Frailes, Maite, Wise, Alan, Powney, Ben, Muir, Alison, McKay, Fiona, Butler, Sharon, Winborn, Kim, Gardner, Christopher, Darton, Jill, Campbell, Colin, Sanger, Gareth
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Digestive system; Gastric Emptying - drug effects; Gastric Emptying - physiology; Ghrelin receptor agonist; Growth hormone secretagogue; Hormones. Endocrine system; Human Growth Hormone - agonists; Humans; Indoles - chemistry; Indoles - pharmacology; Medical sciences; Pharmacology. Drug treatments; Rats; Receptors, Ghrelin - agonists; Receptors, Ghrelin - physiology; Stereoisomerism; Growth hormone secretagogue; Ghrelin receptor agonist; Agonist; Rat; Dyspepsia; Peptide hormone; Pyridine derivatives; Thiophene derivatives; Ghrelin; Chemical synthesis; Biological receptor; Sulfonamide; Somatotropin releasing factor; Rodentia; Ghrelin receptor; Gastric emptying; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Animal; Digestive diseases; Piperazine derivatives; Indole derivatives; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.09.067

A series of indolines showing potent in vitro ghrelin receptor agonism and acceleration of gastric emptying in rats is described. High throughput screening combined with efficient datamining and parallel synthesis led to the discovery of a novel series of indolines showing potent in vitro ghrelin receptor agonist activity and acceleration of gastric emptying in rats.