In:
Chinese Journal of Chemistry, Wiley, Vol. 40, No. 22 ( 2022-11-15), p. 2625-2632
Abstract:
The binding of Sphingosine‐1‐phosphate (S1P) with the S1PR1‐5 plays a fundamental physiological role in a number of processes including vascular development and stabilization, lymphocyte migration and distribution. S1P‐S1PR1 signal axis established roles in immune cell trafficking thus playing a therapeutic role in multiple sclerosis and inflammatory bowel disease. In this study, a series of oxadiazole derivatives were designed and synthesized as S1PR1 agonists based on rational drug design. Among them, compound 9i was identified as a potent and selective S1PR1 agonist with activities on β ‐arrestin recruitment (EC 50 = 0.36 nmol/L) and receptor internalization (EC 50 = 8.09 nmol/L). Meanwhile, compound 9i displayed an oral bioavailability up to 93.6%. Based on its excellent activity to S1PR1 and pharmacokinetic properties, compound 9i effectively alleviated dextran sulfate sodium (DSS)‐induced ulcerative colitis in mice at a dose of 0.1 mg/kg.
Type of Medium:
Online Resource
ISSN:
1001-604X
,
1614-7065
DOI:
10.1002/cjoc.202200392
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2144352-X
SSG:
6,25
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