67808-64-4Relevant articles and documents
Discovery of Novel and Potent N-Methyl- d -aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models
Li, Zhongtang,Cai, Guanxing,Fang, Fan,Li, Wenchao,Fan, Minghua,Lian, Jingjing,Qiu, Yinli,Xu, Xiangqing,Lv, Xuehui,Li, Yiyan,Zheng, Ruqiu,Wang, Yuxi,Li, Zhongjun,Zhang, Guisen,Liu, Zhenming,Huang, Zhuo,Zhang, Liangren
, p. 5551 - 5576 (2021/05/31)
N-Methyl-d-aspartate receptors (NMDARs) are glutamate-gated Na+ and Ca2+-permeable ion channels involved in excitatory synaptic transmission and synaptic plasticity. NMDAR hypofunction has long been implicated in the pathophysiology including major depressive disorders (MDDs). Herein, we report a series of furan-2-carboxamide analogues as novel NMDAR-positive allosteric modulators (PAMs). Through structure-based virtual screen and electrophysiological tests, FS2921 was identified as a novel NMDAR PAM with potential antidepressant effects. Further structure-activity relationship studies led to the discovery of novel analogues with increased potentiation. Compound 32h caused a significant increase in NMDAR excitability in vitro and impressive activity in the forced swimming test. Moreover, compound 32h showed no significant inhibition of hERG or cell viability and possessed a favorable PK/PD profile. Our study presented a series of novel NMDAR PAMs and provided potential opportunities for discovering of new antidepressants.
Chemical switching in reaction behavior of azine: Synthesis of a novel thienodiazepine derivative
Ohtake, Kaoru,Tsuda, Jyunpei,Takatori, Kazuhiko,Nagumo, Shinji,Yasui, Eiko
supporting information, (2021/04/15)
We previously have reported that an acid-promoted condensation of a hydrazonoester derived from phenylalanine afforded an azine which was converted to a pyrrole through 3 steps: isomerization to dienamine, [3,3]-sigmatropic rearrangement, and cyclization.
Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation
Saraswati, A. Prasanth,Relitti, Nicola,Brindisi, Margherita,Osko, Jeremy D.,Chemi, Giulia,Federico, Stefano,Grillo, Alessandro,Brogi, Simone,McCabe, Niamh H.,Turkington, Richard C.,Ibrahim, Ola,O'Sullivan, Jeffrey,Lamponi, Stefania,Ghanim, Magda,Kelly, Vincent P.,Zisterer, Daniela,Amet, Rebecca,Hannon Barroeta, Patricia,Vanni, Francesca,Ulivieri, Cristina,Herp, Daniel,Sarno, Federica,Di Costanzo, Antonella,Saccoccia, Fulvio,Ruberti, Giovina,Jung, Manfred,Altucci, Lucia,Gemma, Sandra,Butini, Stefania,Christianson, David W.,Campiani, Giuseppe
supporting information, p. 2268 - 2276 (2020/12/17)
Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit 6a. We identified compound 6j as the most potent and selective hHDAC6 inhibitor of the series. Biological investigation of compounds 6b, 6h, and 6j demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. 6j induced HDAC6-dependent pSTAT3 inhibition.
