title: Discovery of S1P agonists with a dihydronaphthalene scaffold.
abstract: Structure-activity relationship of sphingosine-1-phosphate receptor agonists was examined. Cinnamyl derivative 1 was modified to improve S1P(1) agonistic activity as well as selectivity over S1P(3) agonistic activity. Dihydronaphthalene derivative 10d was identified as a potent S1P(1) receptor agonist with high selectivity against S1P(3) and enhanced efficacy in lowering peripheral lymphocyte counts in mice.
authors.affiliation: Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. h.kurata@ono.co.jp
authors.forename: Haruto
authors.initials: H
authors.lastname: Kurata
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kusumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Otsuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Masakuni
authors.initials: M
authors.lastname: Kurono
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shioya
authors.forename: Takaki
authors.initials: T
authors.lastname: Komiya
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: D000284:Administration, Oral; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D020005:Propanols / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
chemical_list: D009281:Naphthalenes; D020005:Propanols; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; C020722:cinnamyl alcohol