40137-12-0

Upstream product

• 31618-90-3 diethyl (p-toluenesulfonyloxymethane)phosphonate 
• 3084-40-0 diethyl (1-hydroxymethyl)phosphonate 
• 69770-58-7 diethyl<<(p-chlorophenyl)sulfide>methyl>phosphonate 

Downstream Products

• 40582-81-8 p-Chlorphenyl-2-methyl-1-heptenyl-sulfon 
• 40582-79-4 p-Chlorphenyl-2-methyl-1-propenyl-sulfon 
• 79328-75-9 1-Chloro-4-[((E)-tridec-1-ene)-1-sulfonyl]-benzene 
• 79328-77-1 (1R,4aS)-1-[(E)-2-(4-Chloro-benzenesulfonyl)-vinyl]-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-phenanthrene 
• 6178-26-3 (E)-4-chlorostyryl 4-chlorophenyl sulfone 
• 76859-78-4 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-3-chlorobenzene 
• 56267-73-3 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-4-fluorobenzene 
• 1554271-57-6 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-3-fluorobenzene 
• 1554271-53-2 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-4-trifluoromethylbenzene 
• 1554271-50-9 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-3-trifluoromethylbenzene 
• 1554271-49-6 (E)-1-(2-((4-chlorophenyl)sulfonyl)vinyl)-2-trifluoromethylbenzene 
• 40583-04-8 p-Chlorphenyl-2-(3-aethoxycarbonylcyclohexyl)-propyl-sulfon 

Relevant academic research and scientific papers

Conjugate Addition Reactions of α,β-Unsaturated Ketones with Higher Order, Mixed Organocuprate Reagents, R2Cu(CN)Li2

Conjugate reactions of mixed cuprates R2Cu(CN)Li2 with α,β-unsaturated ketones are reported.These reagents, in most cases, react extremely rapidly affording the corresponding alkylated ketones in high yields.Attempts at trapping the intermediate enolates appeared to be successful using MeI as electrophile; however, the method is not general and was, therefore, not pursued.The effects of solvent and ligand composition on R2Cu(CN)Li2 as well as on the more highly mixed species RTRRCu(CN)Li2 have been examined.The selectivity of ligand transfer in these latter,second generation organocuprates is also discussed.

Development and optimization of halogenated vinyl sulfones as Nrf2 activators for the treatment of Parkinson's disease

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.

NOVEL HALO-(3-(PHENYLSULFONYL)PROP-1-ENYL)PYRIDINE DERIVATIVE AND USE THEREOF

The present invention relates to a novel halo-(3-(phenylsulfonyl)prop-1-enyl)pyridine derivative or a pharmaceutically acceptable salt thereof; a preparation method thereof; and an Nrf2 activator and a pharmaceutical composition for preventing or treating diseases induced by a decrease in Nrf2 activity, both of which comprise the same as an active ingredient.

Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson's disease therapy

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.