Discovery of S1P agonists with a dihydronaphthalene scaffold

Haruto Kurata; Kensuke Kusumi; Kazuhiro Otsuki; Ryo Suzuki; Masakuni Kurono; Yuka Takada; Hiroki Shioya; Takaki Komiya; Hirotaka Mizuno; Takeji Ono; Hiroshi Hagiya; Masashi Minami; Shinji Nakade; Hiromu Habashita

doi:10.1016/j.bmcl.2011.05.029

Discovery of S1P agonists with a dihydronaphthalene scaffold

Bioorg Med Chem Lett. 2011 Jul 1;21(13):3885-9. doi: 10.1016/j.bmcl.2011.05.029. Epub 2011 May 15.

Authors

Haruto Kurata¹, Kensuke Kusumi, Kazuhiro Otsuki, Ryo Suzuki, Masakuni Kurono, Yuka Takada, Hiroki Shioya, Takaki Komiya, Hirotaka Mizuno, Takeji Ono, Hiroshi Hagiya, Masashi Minami, Shinji Nakade, Hiromu Habashita

Affiliation

¹ Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. h.kurata@ono.co.jp

PMID: 21641216
DOI: 10.1016/j.bmcl.2011.05.029

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.

MeSH terms

Administration, Oral
Animals
CHO Cells
Cricetinae
Cricetulus
Fingolimod Hydrochloride
Humans
Lymphocytes / drug effects
Mice
Molecular Structure
Naphthalenes / administration & dosage
Naphthalenes / chemical synthesis*
Naphthalenes / pharmacology
Propanols / administration & dosage
Propanols / chemistry*
Propanols / pharmacology
Propylene Glycols
Receptors, Lysosphingolipid / agonists*
Sphingosine / analogs & derivatives
Structure-Activity Relationship

Substances

Naphthalenes
Propanols
Propylene Glycols
Receptors, Lysosphingolipid
Fingolimod Hydrochloride
Sphingosine
cinnamyl alcohol