Synthesis and evaluation of N-(4-benzylphenyl)piperazines as VGF inducers

Tetsuya Toba; Ryosuke Suzuki; Junko Futamura-Takahashi; Yoshito Kawamoto; Shigeki Tamura; Mariko Kuroda; Yoshiari Shimmyo; Michinori Kadokura; Kazumichi Goto; Teruyoshi Inoue; Tsuyoshi Muto; Hirokazu Annoura

doi:10.1016/j.bmcl.2018.05.047

Synthesis and evaluation of N-(4-benzylphenyl)piperazines as VGF inducers

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2528-2532. doi: 10.1016/j.bmcl.2018.05.047. Epub 2018 May 26.

Affiliations

¹ Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: toba.tetsuya.zh@daiichisankyo.co.jp.
² Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.

PMID: 29871846
DOI: 10.1016/j.bmcl.2018.05.047

Abstract

A series of compounds was discovered that induce the production of VGF mRNA in SH-SY5Y cells and exhibit cytoprotection under tunicamycin induced endoplasmic reticulum (ER) stress. The aminophenol ring and linker chain of the template SUN N8075 (1) was modified to yield compounds with higher efficacy and lower propensity for adverse effects.

Keywords: Cytoprotection; SH-SY5Y; SUN N8075; Structure-activity relationship; VGF inducer.

MeSH terms

Cell Line, Tumor
Cytoprotection
Dose-Response Relationship, Drug
Endoplasmic Reticulum Stress / drug effects
Humans
Molecular Structure
Nerve Growth Factors / biosynthesis*
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / pharmacology*
RNA, Messenger / biosynthesis
Structure-Activity Relationship
Tunicamycin / pharmacology

Substances

Nerve Growth Factors
Piperazines
RNA, Messenger
VGF protein, human
Tunicamycin