Exploratory study of oxatomide derivatives with high P2X7 receptor inhibitory activity

Noriyuki Yamagiwa; Mika Komine; Fumi Hanaoka; Tomoya Nobuta; Kazuki Yoshida; Masaaki Ito; Isao Matsuoka

doi:10.1016/j.bmcl.2022.129035

Exploratory study of oxatomide derivatives with high P2X₇ receptor inhibitory activity

Bioorg Med Chem Lett. 2022 Dec 1:77:129035. doi: 10.1016/j.bmcl.2022.129035. Epub 2022 Oct 22.

Authors

Noriyuki Yamagiwa¹, Mika Komine², Fumi Hanaoka², Tomoya Nobuta², Kazuki Yoshida², Masaaki Ito², Isao Matsuoka³

Affiliations

¹ Takasaki University of Health and Welfare, 60, Nakaorui, Takasaki-city, Gunma 370-0033, Japan. Electronic address: yamagiwa@takasaki-u.ac.jp.
² Takasaki University of Health and Welfare, 60, Nakaorui, Takasaki-city, Gunma 370-0033, Japan.
³ Takasaki University of Health and Welfare, 60, Nakaorui, Takasaki-city, Gunma 370-0033, Japan. Electronic address: isao@takasaki-u.ac.jp.

PMID: 36283612
DOI: 10.1016/j.bmcl.2022.129035

Abstract

Various oxatomide derivatives were designed and synthesized to develop novel P2X₇ receptor (P2X₇R) antagonists. Evaluation for in-vitro P2X₇R antagonist assay showed that DPM-piperazine moiety of oxatomide was required to maintain an inhibitory activity. The structure of both alkyl chains and aromatic head groups strongly affected P2X₇R inhibitory activity, and the analogue, with C4-type saturated alkyl chain and a non-substituted or fluorine-substituted indole, was 7.3 to 6.4 times more potent as a P2X₇R antagonist than oxatomide.

Keywords: Diphenylmethyl; Oxatomide; P2X(7)R.

MeSH terms

Piperazines* / pharmacology
Purinergic P2X Receptor Antagonists / chemistry
Purinergic P2X Receptor Antagonists / pharmacology
Receptors, Purinergic P2X7*

Substances

oxatomide
Piperazines
Receptors, Purinergic P2X7
Purinergic P2X Receptor Antagonists