Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core
Year: 2011
Type: article
Abstract: The optimization of a series of S1P1 agonists with limited activity against S1P3 is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml200252b
Authors: Paul E. Harrington, Michael D. Croghan, Christopher Fotsch, Mike Frohn, Brian A. Lanman, Lewis D. Pennington, Alexander J. Pickrell, Anthony B. Reed, Kelvin K. C. Sham, Andrew Tasker, Heather A. Arnett, Michael Fiorino, Matthew R. Lee, Michele McElvain, Henry G. Morrison, Han Xu, Yang Xu, Xuxia Zhang, Min Wong, Victor J. Cee
Institution: Amgen (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2038793320