Indole-propionic acid derivatives as potent, S1P3-sparing and EAE efficacious sphingosine-1-phosphate 1 (S1P1) receptor agonists

Qinghua Meng; Baowei Zhao; Qiongfeng Xu; Xuesong Xu; Guanghui Deng; Chengyong Li; Linbo Luan; Feng Ren; Hailong Wang; Heng Xu; Yan Xu; Haibo Zhang; Jia-Ning Xiang; John D Elliott; Taylor B Guo; Yonggang Zhao; Wei Zhang; Hongtao Lu; Xichen Lin

doi:10.1016/j.bmcl.2012.02.083

Indole-propionic acid derivatives as potent, S1P3-sparing and EAE efficacious sphingosine-1-phosphate 1 (S1P1) receptor agonists

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2794-7. doi: 10.1016/j.bmcl.2012.02.083. Epub 2012 Mar 3.

Affiliation

¹ Research and Development, GlaxoSmithKline Pharmaceuticals, Pudong, Shanghai, China.

PMID: 22429468
DOI: 10.1016/j.bmcl.2012.02.083

Abstract

Novel indole-propionic acid derivatives were developed as sphingosine-1-phosphate (S1P) receptor agonists through a systematic SAR study. The optimized and S1P(3) selective S1P(1) agonist 9f induced peripheral blood lymphocyte reduction in vivo and has an excellent efficacy in mouse experimental autoimmune encephalomyelitis (EAE).

MeSH terms

Animals
Down-Regulation / drug effects
Encephalomyelitis, Autoimmune, Experimental* / therapy
Indoles / chemistry*
Indoles / pharmacology
Lymphocytes / cytology
Lymphocytes / drug effects
Mice
Molecular Structure
Propionates / chemistry*
Propionates / pharmacology
Receptors, Lysosphingolipid / agonists*
Structure-Activity Relationship

Substances

Indoles
Propionates
Receptors, Lysosphingolipid
propionic acid