2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1-phosphate (S1P) receptor agonists

Vincent J Colandrea; Irene E Legiec; Pei Huo; Lin Yan; Jeffrey J Hale; Sander G Mills; James Bergstrom; Deborah Card; Gary Chebret; Richard Hajdu; Carol Ann Keohane; James A Milligan; Mark J Rosenbach; Gan-Ju Shei; Suzanne M Mandala

doi:10.1016/j.bmcl.2006.03.038

2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1-phosphate (S1P) receptor agonists

Bioorg Med Chem Lett. 2006 Jun 1;16(11):2905-8. doi: 10.1016/j.bmcl.2006.03.038. Epub 2006 Mar 31.

Authors

Vincent J Colandrea¹, Irene E Legiec, Pei Huo, Lin Yan, Jeffrey J Hale, Sander G Mills, James Bergstrom, Deborah Card, Gary Chebret, Richard Hajdu, Carol Ann Keohane, James A Milligan, Mark J Rosenbach, Gan-Ju Shei, Suzanne M Mandala

Affiliation

¹ Department of Medical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. vince_colandrea@merck.com

PMID: 16580205
DOI: 10.1016/j.bmcl.2006.03.038

Abstract

A series of 2,5-cis-disubstituted pyrrolidines were synthesized and evaluated as S1P receptor agonists. Compounds 15-21 were identified with good selectivity over S1P3 which lowered circulating lymphocytes after oral administration in mice.

MeSH terms

Administration, Oral
Animals
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry*
Carboxylic Acids / pharmacology*
Molecular Structure
Pyrrolidines / chemistry*
Rats
Receptors, Lysosphingolipid / agonists*
Receptors, Lysosphingolipid / metabolism
Structure-Activity Relationship

Substances

Carboxylic Acids
Pyrrolidines
Receptors, Lysosphingolipid
pyrrolidine