title: Structure-activity relationship studies of sphingosine-1-phosphate receptor agonists with N-cinnamyl-β-alanine moiety.
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.
authors.affiliation: Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd, Mishima, Osaka 618-8585, Japan. h.kurata@ono.co.jp
authors.forename: Haruto
authors.initials: H
authors.lastname: Kurata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Otsuki
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kusumi
authors.forename: Masakuni
authors.initials: M
authors.lastname: Kurono
authors.forename: Masahiko
authors.initials: M
authors.lastname: Terakado
authors.forename: Takuya
authors.initials: T
authors.lastname: Seko
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Mizuno
authors.forename: Takeji
authors.initials: T
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hagiya
authors.forename: Masashi
authors.initials: M
authors.lastname: Minami
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakade
authors.forename: Hiromu
authors.initials: H
authors.lastname: Habashita
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry; D000068876:Fingolimod Hydrochloride; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015091:beta-Alanine / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002934:Cinnamates; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D015091:beta-Alanine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine