30335-72-9Relevant articles and documents
Synthesis and Anti-neuroinflammatory Activity of Lactone Benzoyl Hydrazine and 2-nitro-1-phenyl-1H-Indole Derivatives as p38α MAPK Inhibitors
Cheng, Bao,Lin, Yongsheng,Kuang, Ming,Fang, Sai,Gu, Qiong,Xu, Jun,Wang, Laiyou
, p. 1121 - 1130 (2015)
Inhibition of p38 mitogen-activated protein kinases (MAPKs) would allow significant modulation of the neuroinflammation condition associated with Alzheimer's disease (AD). Inspired from the pharmacophore of natural NF-κB and p38α MAPK inhibitor 5,6-dehydrokawain and p38α MAPK inhibitors 1a, 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas, and 1b, a class of indole-pyrimidinyl compounds which were patented respectively, we designed, de novo synthesized, and evaluated two kinds of novel series of lactone benzoyl hydrazine derivatives and 2-nitro-1-phenyl-1H-indole derivatives in an effort to develop pharmacologically tractable agents to alleviate the progression of AD. Fourteen of the seventeen synthesized compounds exhibit significant inhibitory effect on the nitric oxide (NO) production induced by lipopolysaccharide (LPS)-induced microglia activation with IC50 less than the control 5,6-dehydrokawain. Notably, compound 27, 6-methoxy-2-nitro-1-(1H-1, 2, 3-triazol-1-yl)-1H-indole, with IC50 values of 1.6 μm can markedly inhibit p38α MAPK and NO release in BV-2 microglial cells. The molecular dynamic (MD) simulations demonstrate that compound 27 inhibits p38α MAPK through binding to the Glu71 and Asp168 residues. Moreover, in vitro study shows that all compounds can easily cross the blood-brain barrier (BBB) and did not exhibit any acute cellular toxicity checked by MTT assay. These investigations provide promising chemical lead candidate as anti-neuroinflammatory agents for AD. We designed, synthesized and evaluated two series lactone benzoyl hydrazine and 2-nitro-1-phenyl-1H-Indole derivatives for novel promising chemical lead p38α MAPK inhibitors as anti-neuroinflammatory agents in fighting against Alzheimer's diseases.
Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2?+?2?+?2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi
Wood, James M.,Satam, Nishikant S.,Almeida, Renata G.,Cristani, Vinicius S.,de Lima, Dênis P.,Dantas-Pereira, Luiza,Salom?o, Kelly,Menna-Barreto, Rubem F.S.,Namboothiri, Irishi N.N.,Bower, John F.,da Silva Júnior, Eufranio N.
, (2020/06/23)
Rhodium-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulations and nitroalkene reactions have been employed for the synthesis of 56 quinone-based compounds. These were evaluated against Trypanosoma cruzi, the parasite that causes Chagas disease. The reactions described here are part of a program that aims to utilize modern, versatile and efficient synthetic methods for the one or two step preparation of trypanocidal compounds. We have identified 9 compounds with potent activity against the parasite; 3 of these were 30-fold more potent than benznidazole (Bz), a drug used for the treatment of Chagas disease. This article provides a comprehensive outline of reactions involving over 120 compounds aimed at the discovery of new quinone-based frameworks with activity against T. cruzi.
Phosphine-Catalyzed Enantioselective Dearomative [3+2]-Cycloaddition of 3-Nitroindoles and 2-Nitrobenzofurans
Wang, Huamin,Zhang, Junyou,Tu, Youshao,Zhang, Junliang
, p. 5422 - 5426 (2019/03/17)
Over the past years, the metal-catalyzed dearomative cycloaddition of 3-nitroindoles and 2-nitrobenzofurans have emerged as a powerful protocol to construct chiral fused heterocyclic rings. However, organocatalytic dearomative reaction of these two classe