16732-70-0Relevant articles and documents
Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer
Wang, Lei,Fang, Kun,Cheng, Junfei,Li, Yu,Huang, Yahui,Chen, Shuqiang,Dong, Guoqiang,Wu, Shanchao,Sheng, Chunquan
, p. 696 - 713 (2020/02/04)
Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.
Carboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
Ren, Long,Nan, Guanglei,Wang, Yongcheng,Xiao, Zhiyan
, p. 14472 - 14488 (2018/11/23)
The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the density functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C-H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.
Substituted indole - 2 - formic acid (by machine translation)
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Paragraph 0050; 0052, (2017/10/28)
This invention relates to a substituted indole - 2 - carboxylic acid synthesis method, is to replace the phenyl hydrazine hydrochloride or arylhydrazines as raw materials, through with pyruvic acid ethyl ester cheng zong, Fischer indole synthesis by reaction of substituted indole - 2 - carboxylic acid ethyl ester, hydrolysis to obtain the substituted - 2 - carboxylic acid. Product purity is greater than 97%, the reaction yield is 64%. Synthesis method of the invention with non-harsh conditions, the operation is simple, and environmental friendliness, it has certain economic benefits. It is a kind of raw materials are easy, simple operation, three wastes, high yield of indole - 2 - carboxylic acid synthesis method. (by machine translation)