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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025730 | PMC |
| http://dx.doi.org/10.1021/ml200252b | DOI Listing |
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