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

[Display omitted] •Derivatives of 1 as VGF inducers are disclosed, and their SAR is discussed.•VGF mRNA induction and cytoprotective activity shifted in a near-parallel manner.•Compounds such as 27 were obtained with enhanced efficacy and reduced risk of MBI. A series of compounds was discovered tha...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2018-08, Vol.28 (14), p.2528-2532
Main Authors: Toba, Tetsuya, Suzuki, Ryosuke, Futamura-Takahashi, Junko, Kawamoto, Yoshito, Tamura, Shigeki, Kuroda, Mariko, Shimmyo, Yoshiari, Kadokura, Michinori, Goto, Kazumichi, Inoue, Teruyoshi, Muto, Tsuyoshi, Annoura, Hirokazu
Format: Article
Language:English
Subjects:
Cytoprotection
SH-SY5Y
Structure-activity relationship
SUN N8075
VGF inducer
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Summary:[Display omitted] •Derivatives of 1 as VGF inducers are disclosed, and their SAR is discussed.•VGF mRNA induction and cytoprotective activity shifted in a near-parallel manner.•Compounds such as 27 were obtained with enhanced efficacy and reduced risk of MBI. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2018.05.047