title: Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.
abstract: Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.
authors: Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. petr_vachal@merck.com
authors: Petr
authors: P
authors: Vachal
authors: Leslie M
authors: LM
authors: Toth
authors: Jeffrey J
authors: JJ
authors: Hale
authors: Lin
authors: L
authors: Yan
authors: Sander G
authors: SG
authors: Mills
authors: Gary L
authors: GL
authors: Chrebet
authors: Carol A
authors: CA
authors: Koehane
authors: Richard
authors: R
authors: Hajdu
authors: James A
authors: JA
authors: Milligan
authors: Mark J
authors: MJ
authors: Rosenbach
authors: Suzanne
authors: S
authors: Mandala