Discovery of Potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P1) Receptor Agonists with Exceptional Selectivity against S1P2 and S1P3

Autor:	Bergstrom James D, Carol Ann Keohane, Suzanne M. Mandala, Stephen A. Parent, Sander G. Mills, Elizabeth J. Quackenbush, L. Alexandra Wickham, Mark Rosenbach, Hugh Rosen, Weirong Chen, Christopher L. Lynch, Rose M. Evans, Hugo M. Vargas, Jeffrey J. Hale, Deborah Card, Gan-Ju Shei, Michael J. Forrest, Gary L. Chrebet, Zhen Li, Richard Hajdu, James A. Milligan
Rok vydání:	2005
Předmět:	Agonist medicine.drug_class Oxadiazole CHO Cells Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Cricetulus Dogs In vivo Cricetinae Drug Discovery medicine Animals Structure–activity relationship Lymphocyte Count Sphingosine-1-phosphate Receptor IC50 Oxadiazoles Graft Survival Skin Transplantation In vitro Rats Receptors Lysosphingolipid chemistry Biochemistry Rats Inbred Lew Molecular Medicine Immunosuppressive Agents
Zdroj:	Journal of Medicinal Chemistry. 48:6169-6173
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm0503244
Popis:	A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 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 S1P3 receptor agonism is not a component of immunosuppressive efficacy.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6d306a8abcaf4018d008bb39f3c5027 https://doi.org/10.1021/jm0503244 Zobrazit plný text záznamu