Discovery of thiadiazole amides as potent, S1P₃-sparing agonists of sphingosine-1-phosphate 1 (S1P₁) receptor

Heng Xu; Haibo Zhang; Linbo Luan; Yan Xu; Chengyong Li; Yonghui Wang; Fangbin Han; Ting Yang; Feng Ren; Jia-Ning Xiang; John D Elliott; Yonggang Zhao; Taylor B Guo; Hongtao Lu; Wei Zhang; David Hirst; Matthew Lindon; Xichen Lin

doi:10.1016/j.bmcl.2012.02.016

Discovery of thiadiazole amides as potent, S1P₃-sparing agonists of sphingosine-1-phosphate 1 (S1P₁) receptor

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2456-9. doi: 10.1016/j.bmcl.2012.02.016. Epub 2012 Feb 15.

Authors

Heng Xu¹, Haibo Zhang, Linbo Luan, Yan Xu, Chengyong Li, Yonghui Wang, Fangbin Han, Ting Yang, Feng Ren, Jia-Ning Xiang, John D Elliott, Yonggang Zhao, Taylor B Guo, Hongtao Lu, Wei Zhang, David Hirst, Matthew Lindon, Xichen Lin

Affiliation

¹ GlaxoSmithKline Pharmaceuticals, R&D China, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201023, China.

PMID: 22386243
DOI: 10.1016/j.bmcl.2012.02.016

Abstract

High-throughput screening of GSK compound collection led to the discovery of a novel series of thiadiazole amides as potent and S1P(3)-sparing sphingosine-1-phosphate 1 (S1P(1)) receptor agonists. Synthesis, structure and activity relationship, selectivity, and some developability properties are described.

MeSH terms

Amides / chemistry*
Amides / pharmacology
Animals
Drug Discovery
High-Throughput Screening Assays
Humans
Immunologic Factors / chemistry*
Immunologic Factors / pharmacology
Lymphocytes / drug effects
Lymphocytes / immunology
Mice
Receptors, Lysosphingolipid / agonists*
Receptors, Lysosphingolipid / chemistry
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology
Structure-Activity Relationship
Thiadiazoles / chemistry*
Thiadiazoles / pharmacology

Substances

Amides
Immunologic Factors
Receptors, Lysosphingolipid
Small Molecule Libraries
Thiadiazoles