Ago-allosteric modulators of human glucagon-like peptide 2 receptor

Kazuto Yamazaki; Hiroki Terauchi; Daisuke Iida; Hironori Fukumoto; Shuichi Suzuki; Takaki Kagaya; Mika Aoki; Koichiro Koyama; Takashi Seiki; Kazuma Takase; Misako Watanabe; Tohru Arai; Kappei Tsukahara; Junichi Nagakawa

doi:10.1016/j.bmcl.2012.08.026

Ago-allosteric modulators of human glucagon-like peptide 2 receptor

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6126-35. doi: 10.1016/j.bmcl.2012.08.026. Epub 2012 Aug 14.

Authors

Kazuto Yamazaki¹, Hiroki Terauchi, Daisuke Iida, Hironori Fukumoto, Shuichi Suzuki, Takaki Kagaya, Mika Aoki, Koichiro Koyama, Takashi Seiki, Kazuma Takase, Misako Watanabe, Tohru Arai, Kappei Tsukahara, Junichi Nagakawa

Affiliation

¹ Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. k5-yamazaki@hhc.eisai.co.jp

PMID: 22944117
DOI: 10.1016/j.bmcl.2012.08.026

Abstract

Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor (GPCR). Few synthetic agonists have been reported so far for class-B GPCRs. Here, we report the first scaffold compounds of ago-allosteric modulators for human GLP-2R, derived from methyl 2-{[(2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1).

MeSH terms

Benzoates / chemical synthesis
Benzoates / chemistry
Benzoates / pharmacology*
Dose-Response Relationship, Drug
Glucagon-Like Peptide-2 Receptor
Humans
Molecular Structure
Receptors, Glucagon / agonists*
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry
Thiophenes / pharmacology*

Substances

Benzoates
Glucagon-Like Peptide-2 Receptor
Receptors, Glucagon
Thiophenes
methyl 2-(((2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino)ethyl)sulfanyl)benzoate