69770-58-7Relevant articles and documents
Electrochemical partial fluorination of organic compounds. 80. Synthesis of cyclic α-arylthio-α-monofluorophosphonate esters
Cao, Yi,Hidaka, Asami,Tajima, Toshiki,Fuchigami, Toshio
, p. 9614 - 9617 (2005)
Seven-membered cyclic α-monofluorophosphonate esters such as 2-allyloxy-3-fluoro-3-phenylthio-4,7-dihydro-[1, 2]-oxaphosphinine-2-oxide were successfully synthesized in moderate total yield as 41% from open-chain allyl phosphonates having an α-arylthio group as an electroauxiliary using an alternative sequence of anodic fluorination and ring-closing olefin metathesis (RCM). On the other hand, in an attempt to synthesize an eight-membered analogue, a different type of seven-membered fluorinated cyclic product was formed predominantly by the RCM reaction between the allyloxy groups.
Development and optimization of halogenated vinyl sulfones as Nrf2 activators for the treatment of Parkinson's disease
Choi, Ji Won,Kim, Siwon,Yoo, Jong Seok,Kim, Hyeon Jeong,Kim, Hyeon Ji,Kim, Byung Eun,Lee, Elijah Hwejin,Lee, Yong Sup,Park, Jong-Hyun,Park, Ki Duk
supporting information, (2021/01/06)
The Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a pivotal role in the cellular defense system against oxidative stress by inducing antioxidant and anti-inflammatory effects. We previously developed Nrf2 activators that potentially protect the death of dopaminergic (DAergic) neuronal cells against oxidative stress in Parkinson's disease (PD). In this study, we designed and synthesized a class of halogenated vinyl sulfones by inserting halogens and pyridine to maximize Nrf2 activation efficacy. Among the synthesized compounds, (E)-3-chloro-2-(2-((2-chlorophenyl)sulfonyl)vinyl)pyridine (9d) significantly exhibited potent Nrf2 activating efficacy (9d: EC50 = 26 nM) at least 10-fold compared with the previous developed compounds (1 and 2). Furthermore, treating with 9d remarkably increased Nrf2 nuclear translocation and Nrf2 protein levels in microglial BV-2 cells. 9d was shown to induce the expression of antioxidant response genes HO-1, GCLC, GCLM, and SOD-1 at both the mRNA and protein levels and suppress proinflammatory cytokines and enzymes. Also, 9d remarkably protected DAergic neurons and restored the PD-associated motor dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model.
Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson's disease therapy
Woo, Seo Yeon,Kim, Ji Hyun,Moon, Mi Kyeong,Han, Se-Hee,Yeon, Seul Ki,Choi, Ji Won,Jang, Bo Ko,Song, Hyo Jung,Kang, Yong Gu,Kim, Jin Woo,Lee, Jaeick,Kim, Dong Jin,Hwang, Onyou,Park, Ki Duk
supporting information, p. 1473 - 1487 (2014/03/21)
Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2 signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.
