Tetrahydroquinoline glucocorticoid receptor agonists: Discovery of a 3-hydroxyl for improving receptor selectivity

✍ Scribed by Steven L. Roach; Robert I. Higuchi; Andrew R. Hudson; Mark E. Adams; Peter M. Syka; Dale E. Mais; Jeffrey N. Miner; Keith B. Marschke; Lin Zhi

• Book ID: 104005121
• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 1020 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.11.047

✦ Synopsis

We have previously disclosed a series of glucocorticoid receptor (GR) ligands derived from 6-indole-1,2,3,4-tetrahydroquinolines through structure-activity relationship (SAR) of the pendent C6-indole ring. In parallel with this effort, we now report SAR of the tetrahydroquinoline A-ring that identified the importance of a C3 hydroxyl in improving GR selectivity within a series of non-steroidal GR agonists.