6287-83-8Relevant articles and documents
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study
Xu, Li-Li,Zhu, Jun-Feng,Xu, Xiao-Li,Zhu, Jie,Li,Xi, Mei-Yang,Jiang, Zheng-Yu,Zhang, Ming-Ye,Liu, Fang,Lu, Meng-Chen,Bao, Qi-Chao,Li, Qi,Zhang, Chao,Wei, Jin-Lian,Zhang, Xiao-Jin,Zhang, Lian-Shan,You, Qi-Dong,Sun, Hao-Peng
, p. 5419 - 5436 (2015)
Induction of phase II antioxidant enzymes by activation of Nrf2/ARE pathway has been recognized as a promising strategy for the regulation of oxidative stress-related diseases. Herein we report our effort on the discovery and optimization of Nrf2 activators with 1,2,4-oxadiazole core. Screening of an in-house collection containing 7500 compounds by ARE-luciferase reporter assay revealed a moderate Nrf2 activator, 1. Aimed at obtaining more derivatives efficiently, molecular similarity search by the combination of 2D fingerprint-based and 3D shape-based search was applied to virtually screening the Chemdiv collection. Three derivatives with the same core were identified to have better inductivity of Nrf2 than 1. The best hit 4 was selected as starting point for structurally optimization, leading to a much more potent derivative 32. It in vitro upregulated gene and protein level of Nrf2 as well as its downstream markers such as NQO1, GCLM, and HO-1. It remarkably suppressed inflammation in the in vivo LPS-challenged mouse model. Our results provide a new chemotype as Nrf2-ARE activators which deserve further optimization with the aim to obtain active anti-inflammatory agents through Nrf2-ARE pathway.
Visible-light-induced aerobic oxidative desulfurization of 2-mercaptobenzimidazolesviaa sulfinyl radical
Deng, Guo-Jun,Fu, Mei,Huang, Huawen,Ji, Xiaochen,Li, Yongtong
supporting information, p. 5594 - 5598 (2020/09/21)
A mild transition-metal-free non-toxic aerobic photoredox system was found to enable highly efficient desulfurization of 2-mercaptobenzimidazoles. This viable catalytic system includes Rose Bengal in a low catalyst loading as a photosensitizer and cheap, non-toxic NaCl in a catalytic amount as an additive, combined with an oxygen atmosphere. This protocol provides an important alternative access to a broad range of benzimidazole and deuterated benzimidazole products in generally high yields with good tolerance of various synthetically and pharmaceutically useful functionalities. The mechanistic studies reveal that both single electron transfer and energy transfer probably occur in the initial step and a sulfinyl radical intermediate is involved in the key desulfurization process.
Synthesis method of ammonium acetate mediated benzimidazole compound
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Paragraph 0048-0050, (2020/11/23)
The invention discloses a synthesis method of a benzimidazole compound mediated by ammonium acetate. The synthesis method comprises the following steps: adding an o-phenylenediamine compound, dimethylsulfoxide, an additive 1 and an additive 2 into a reaction tube, carrying out a stirring reaction at 130-150 DEG C, cooling the reaction product to room temperature after the reaction is finished, and carrying out separation and purification on the product to obtain the benzimidazole compound. The invention develops a method for synthesizing a benzimidazole compound under the mediation of ammonium acetate by taking DMSO as a carbon source and an oxidant and an o-phenylenediamine compound as a substrate under the condition of no metal catalyst. The synthesis method does not need a metal catalyst, and the required carbon source and oxidant have the characteristics of low toxicity, low price, easiness in obtaining, stable performance and the like. The method has the advantages of easiness inoperation, few steps, mild reaction conditions, better functional group tolerance and the like, and provides a new valuable way for synthesizing benzimidazole compounds.
Facile access to: N-formyl imide as an N-formylating agent for the direct synthesis of N-formamides, benzimidazoles and quinazolinones
Huang, Hsin-Yi,Liang, Chien-Fu,Lin, Xiu-Yi,Yen, Shih-Yao
supporting information, p. 5726 - 5733 (2020/08/21)
N-Formamide synthesis using N-formyl imide with primary and secondary amines with catalytic amounts of p-toluenesulfonic acid monohydrate (TsOH·H2O) is described. This reaction is performed in water without the use of surfactants. Moreover, N-formyl imide is efficiently synthesized using acylamidines with TsOH·H2O in water. In addition, N-formyl imide was successfully used as a carbonyl source in the synthesis of benzimidazole and quinazolinone derivatives. Notable features of N-formylation of amines by using N-formyl imide include operational simplicity, oxidant- A nd metal-free conditions, structurally diverse products, and easy applicability to gram-scale operation.
