Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3

被引：92

作者：

Li, Z ^{[1
]}

Chen, WR

Hale, JJ

Lynch, CL

Mills, SG

Hajdu, R

Keohane, CA

Rosenbach, MJ

Milligan, JA

Shei, GJ

Chrebet, G

Parent, SA

Bergstrom, J

Card, D

Forrest, M

Quackenbush, EJ

Wickham, LA

Vargas, H

Evans, RM

Rosen, H

Mandala, S

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Rheumatol Res, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Preclin Safety Evaluat, West Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 20期

关键词：

D O I：

10.1021/jm0503244

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P(1)) receptor agonists with minimal affinity for the S1P(2) and S1P3 receptor subtypes. Analogue 26 (S1P(1) IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P(3) receptor agonism is not a component of inummosuppressive efficacy.

引用

页码：6169 / 6173

页数：5

共 28 条

[21] Sphingosine 1-phosphate and lysophosphatidic acid receptors: agonist and antagonist binding and progress toward development of receptor-specific ligands [J].