Alkylsulfanyl analogs as potent α2δ ligands

Kousei Shimada; Yasuo Ohata; Jun Kobayashi; Yoshiyuki Onishi; Asuka Kawamura; Yuki Domon; Naohisa Arakawa; Tatsuya Inoue; Yutaka Kitano; Fumihiko Matsuda; Yuki Abe; Tsuneo Deguchi

doi:10.1016/j.bmcl.2018.05.006

Alkylsulfanyl analogs as potent α₂δ ligands

Bioorg Med Chem Lett. 2018 Jun 15;28(11):2000-2002. doi: 10.1016/j.bmcl.2018.05.006. Epub 2018 May 4.

Authors

Affiliations

¹ R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: shimada.kousei.ah@daiichisankyo.co.jp.
² Daiichi Sankyo RD Novare Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
³ R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

PMID: 29752183
DOI: 10.1016/j.bmcl.2018.05.006

Abstract

We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics.

Keywords: Alkylsulfanyl; Analgesic; Diabetes; α(2)δ; γ-Amino acid.

MeSH terms

Animals
Calcium Channels / metabolism*
Caproates / chemistry
Caproates / pharmacology
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / metabolism
Diabetes Mellitus, Type 1 / drug therapy*
Diabetes Mellitus, Type 1 / metabolism
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / metabolism
Disease Models, Animal
Ligands
Mice
Molecular Structure
Neuralgia / drug therapy*
Neuralgia / metabolism
Sulfhydryl Compounds / chemistry
Sulfhydryl Compounds / pharmacology*

Substances

Calcium Channels
Caproates
Ligands
Sulfhydryl Compounds
voltage gated calcium channel subunit Ca alpha2delta-1, human
hexanoic acid