2596-93-2Relevant articles and documents
Design, synthesis and anticancer evaluation of 3-methyl-1H-indazole derivatives as novel selective bromodomain-containing protein 4 inhibitors
Dong, Ru,Zhang, Cheng,Wang, Chao,Zhou, Xin,Li, Wen,Zhang, Jin-Yang,Wang, Min,Xu, Yong,Sun, Li-Ping
, (2022/01/11)
Bromodomain-containing Protein 4 (BRD4), an ‘epigenetic reader’, regulates chromatin structure and gene expression via recognizing and binding acetylated lysine in histones. BRD4 has become a therapeutic target for cancers because it promotes the expression of the tumor genes, such as c-Myc, NF-κB, and Bcl-2. In this study, a new series of 3-methyl-1H-indazole derivatives were designed via virtual screening and structure-based optimization. All compounds were synthesized and evaluated for their inhibitory activities to BRD4-BD1 and their antiproliferative effects in cancer cell lines. Among them, several compounds (such as 9d, 9u and 9w) exhibited strong BRD4-BD1 affinities and inhibition activities, and potently suppressed MV4;11 cancer cell line proliferation. Among them, compound 9d showed excellent selectivity for BRD4 and effectively suppressed c-Myc, the downstream protein of BRD4. This study provided new lead compounds for further biological evaluation on BRD4.
HCl-mediated transamidation of unactivated formamides using aromatic amines in aqueous media
Dhawan, Sanjeev,Girase, Pankaj Sanjay,Kumar, Vishal,Karpoormath, Rajshekhar
, p. 3729 - 3739 (2021/10/14)
We report transamidation protocol to synthesize a range of secondary and tertiary amides from weakly nucleophilic aromatic and hetero-aryl amines with low reactive formamide derivatives, utilizing hydrochloric acid as catalyst. This current acid mediated strategy is beneficial because it eliminates the need for a metal catalyst, promoter or additives in the reaction, simplifies isolation and purification. Notably, this approach conventionally used to synthesize molecules on gram scales with excellent yields and a high tolerance for functional groups.
A NHC-silyliumylidene cation for catalytic N?formylation of amines using carbon dioxide
Leong, Bi-Xiang,Teo, Yeow-Chuan,Condamines, Cloe,Yang, Ming-Chung,Su, Ming-Der,So, Cheuk-Wai
, p. 14824 - 14833 (2020/12/21)
This study describes the use of a silicon(II) complex, namely, the NHC-silyliumylidene cation complex [(IMe)2SiH]I (1, IMe =:C{N(Me)C(Me)}2), to catalyze the chemoselective N-formylation of primary and secondary amines using CO2 and PhSiH3 under mild conditions to afford the corresponding formamides as a sole product (average reaction time: 4.5 h; primary amines, average yield: 95%, average TOF: 8 h?1; secondary amines, average yield: 98%, average TOF: 17 h?1). The activity of 1 and product yields outperform the currently available non-transition-metal catalysts used for this catalysis. Mechanistic studies show that the silicon(II) center in complex 1 catalyzes the C?N bond formation via a different pathway in comparison with non-transition-metal catalysts. It sequentially activates CO2, PhSiH3, and amines, which proceeds via a dihydrogen elimination mechanism, to form formamides, siloxanes, and dihydrogen gas.
