Structure-activity relationship studies of sphingosine-1-phosphate receptor agonists with N-cinnamyl-β-alanine moiety

Haruto Kurata; Kazuhiro Otsuki; Kensuke Kusumi; Masakuni Kurono; Masahiko Terakado; Takuya Seko; Hirotaka Mizuno; Takeji Ono; Hiroshi Hagiya; Masashi Minami; Shinji Nakade; Hiromu Habashita

doi:10.1016/j.bmcl.2011.01.029

Structure-activity relationship studies of sphingosine-1-phosphate receptor agonists with N-cinnamyl-β-alanine moiety

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1390-3. doi: 10.1016/j.bmcl.2011.01.029. Epub 2011 Jan 11.

Authors

Haruto Kurata¹, Kazuhiro Otsuki, Kensuke Kusumi, Masakuni Kurono, Masahiko Terakado, Takuya Seko, Hirotaka Mizuno, Takeji Ono, Hiroshi Hagiya, Masashi Minami, Shinji Nakade, Hiromu Habashita

Affiliation

¹ Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd, Mishima, Osaka 618-8585, Japan. h.kurata@ono.co.jp

PMID: 21295477
DOI: 10.1016/j.bmcl.2011.01.029

Abstract

Structure-activity relationship of sphingosine-1-phosphate receptor agonist was examined. In terms of reducing the flexibility of molecule, hit compound 1 was modified to improve S1P(1) agonistic activity as well as selectivity over S1P(3) agonistic activity. Novel S1P agonists with cinnamyl scaffold or 1,2,5,6-tetrahydropyridine scaffold were identified.

MeSH terms

Animals
Cinnamates / chemical synthesis*
Cinnamates / chemistry
Fingolimod Hydrochloride
Propylene Glycols / chemistry
Propylene Glycols / pharmacology
Rats
Receptors, Lysosphingolipid / agonists*
Sphingosine / analogs & derivatives
Sphingosine / chemistry
Sphingosine / pharmacology
Structure-Activity Relationship
beta-Alanine / chemical synthesis*
beta-Alanine / chemistry

Substances

Cinnamates
Propylene Glycols
Receptors, Lysosphingolipid
beta-Alanine
Fingolimod Hydrochloride
Sphingosine