216955-76-9Relevant articles and documents
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator
Choi, Ji Won,Shin, Su Jeong,Kim, Hyeon Ji,Park, Jong-Hyun,Kim, Hyeon Jeong,Lee, Elijah Hwejin,Pae, Ae Nim,Bahn, Yong Sun,Park, Ki Duk
supporting information, p. 1061 - 1067 (2019/06/24)
The main pathway responsible for cellular regulation against oxidative stress is nuclear factor E2-related factor-2 (Nrf2) signaling. We previously synthesized and reported a novel vinyl sulfone (1) as an Nrf2 activator with therapeutic potential for Parkinson's disease (PD). In this study, we changed the vinyl sulfone to vinyl sulfonamide or vinyl sulfonate to improve Nrf2 activating efficacy. We observed that the introduction of vinyl sulfonamide led to a reduction of the effects on Nrf2 activation, whereas vinyl sulfonate compounds exhibited superior activity compared to the vinyl sulfone compounds. Among the vinyl sulfonates, 3c exhibited 6.9- and 83.5-fold higher effects on Nrf2 activation than the corresponding vinyl sulfone (1) and vinyl sulfonamide (2c), respectively. Compound 3c was confirmed to induce expression of the Nrf2-dependent antioxidant enzymes at the protein level in cells. In addition, 3c mitigated PD-associated behavioral deficits by protecting DAergic neurons in the MPTP-induced mouse model of PD.
Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases
Siles, Rogelio,Kawasaki, Yuko,Ross, Patrick,Freire, Ernesto
supporting information; experimental part, p. 5305 - 5309 (2011/10/03)
A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (Ki = 880 nM) and significant selectivity against other human related serine proteases like trypsin (Ki = 729 μM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.
Synthesis and structure-activity relationships in a series of ethenesulfonamide derivatives, a novel class of endothelin receptor antagonists
Harada, Hironori,Kazami, Jun-Ichi,Watanuki, Susumu,Tsuzuki, Ryuji,Sudoh, Katsumi,Fujimori, Akira,Tokunaga, Tatsuhiro,Tanaka, Akihiro,Tsukamoto, Shin-Ichi,Yanagisawa, Isao
, p. 1593 - 1603 (2007/10/03)
In the previous paper, we described a series of the 2-arylethenesulfonamide derivatives, a novel class of ETA-selective endothelin (ET) receptor antagonists, including the compounds 1a, b. Compound 1a showed excellent oral antagonistic activities and pharmacokinetic profiles, and the monopotassium salt of 1 (YM-598 monopotassium) is in clinical trials. In this paper, we wish to report the investigation of the further details of structure-activity relationships (SARs) of the 2-phenylethenesulfonamide region in 1a. It was found that methyl substitutions at the 2-, 4- and 6-positions of the phenyl group in 1a led to the discovery of the ETA/ETB mixed antagonist (6s) with an IC50 of 2.2 nM for the ETA receptor. We also found that introduction of an ethyl group to the 1-position of the ethenyl group in 1a gave the ETA selective antagonist (6u) with an oral endothelin antagonistic activity in rats.
