89896-39-9Relevant articles and documents
Design, synthesis and antitumor evaluations of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors
Sun, Qinsheng,Dai, Qiuzi,Zhang, Cunlong,Chen, Yan,Zhao, Lei,Yuan, Zigao,Jiang, Yuyang
supporting information, p. 2479 - 2483 (2021/03/08)
DNA methyltransferase (DNMT) and histone deacetylase (HDAC) are well recognized epigenetic targets for discovery of antitumor agents. In this study, we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors. MTT assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels, inducing hypomethylation of p16 and hyperacetylation of histones H3K9 and H4K8. Besides, 204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle arrest. Molecular docking models explained the functional mechanism of 204 inhibiting DNMT1 and HDAC. Preliminary studies on metabolic profiles revealed that 204 showed desirable stability in liver microsomes. Our study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.
Schmidt Reaction of ω-Azido Valeryl Chlorides Followed by Intermolecular Trapping of the Rearrangement Ions: Synthesis of Assoanine and Related Pyrrolophenanthridine Alkaloids
DIng, Shao-Lei,Ji, Yang,Su, Yan,Li, Rui,Gu, Peiming
, p. 2012 - 2021 (2019/02/14)
The Schmidt reaction of ω-azido valeryl chlorides in the presence of an additional nucleophile was explored. The arenes, alcohols, and amines were demonstrated as the intermolecular trapping reagents for isocyanate ion and N-acyliminium ion from the Schmidt rearrangement, affording the corresponding products with moderate to excellent yields. Two 2-oxoindoles from the reaction were successfully converted into four natural alkaloids, namely, assoanine, anhydrolycorine, oxoassoanine, and anhydrolycorinone.
N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides
Shing, Ka-Pan,Liu, Yungen,Cao, Bei,Chang, Xiao-Yong,You, Tingjie,Che, Chi-Ming
supporting information, p. 11947 - 11951 (2018/09/11)
Metal-catalyzed intramolecular C?H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N-heterocyclic carbene ligands which catalyzes the intramolecular C(sp3)–H amination of a wide variety of alkyl azides under microwave-assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C?H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re-bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis-octahydroindole, and leelamine derivatives.
