Park, Sun Jun Yeon, Seul Ki Yoowon Kim Kim, Hyeon Jeong KIm Si Won KIM, JU SHIN Choi, Ji Won Byung, Eun Kim Elijah, Hwejin Lee Kim Ri-um SEO, SEON HEE Lee, Jae Ick Jun Woo Kim Ha-Yeon Lee Hayoung Hwang Yong-Sun Bahn Eunji Cheong Park, Jong Hyun Park, Ki Duk 2024-01-12T03:32:29Z 2024-01-12T03:32:29Z 2022-03-16 2022-02 0022-2623 https://pubs.kist.re.kr/handle/201004/76794 The sphingosine-1-phosphate-1 (S1P1) receptor agonists have great potential for the treatment of multiple sclerosis (MS) because they can inhibit lymphocyte egress through receptor internalization. We designed and synthesized triazole and isoxazoline derivatives to discover a novel S1P1agonist for MS treatment. Of the two scaffolds, the isoxazoline derivative was determined to have excellent in vitro efficacy and drug-like properties. Among them, compound 21l was found to have superior drug-like properties as well as excellent in vitro efficacies (EC50= 7.03 nM in β-arrestin recruitment and EC50= 11.8 nM in internalization). We also confirmed that 21l effectively inhibited lymphocyte egress in the peripheral lymphocyte count test and significantly improved the clinical score in the experimental autoimmune encephalitis MS mouse model. ？ 2022 American Chemical Society. All rights reserved. English American Chemical Society Discovery of Novel Sphingosine-1-Phosphate-1 Receptor Agonists for the Treatment of Multiple Sclerosis Article 10.1021/acs.jmedchem.1c01979 1 Journal of Medicinal Chemistry, v.65, no.4, pp.3539 - 3562 Journal of Medicinal Chemistry 65 4 3539 3562 N scie scopus 000797940600048 2-s2.0-85124131577 Chemistry, Medicinal Pharmacology & Pharmacy Article LYMPHOCYTE EGRESS S1P(1) POTENT MODULATOR OZANIMOD IDENTIFICATION OPTIMIZATION DISEASE FTY720 ASSAY