29640-13-9Relevant articles and documents
Taub,Hino
, p. 106 (1964)
Discovery of N 1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7 H -pyrrolo[2,3- d] pyrimidin-2-yl)amino)phenyl)- N 8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer
Li, Yongtao,Luo, Xiaohe,Guo, Qingxiang,Nie, Yongwei,Wang, Tianqi,Zhang, Chao,Huang, Zhi,Wang, Xin,Liu, Yanhua,Chen, Yanan,Zheng, Jianyu,Yang, Shengyong,Fan, Yan,Xiang, Rong
, p. 3166 - 3192 (2018/04/23)
A series of novel, highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d] pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide (6e) was discovered. The lead compound 6e with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, respectively, can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound 6e showed excellent selectivity and specificity. Compound 6e induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with 6e showed significant antitumor efficacy. The insight into mechanisms of 6e indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. Our data demonstrated the novel compound 6e could be a promising drug candidate for cancer therapy.
Aminosaeuren, I. Darstellung von Aminosaeuren aus Halogencarbonsaeure-alkylestern mit Alkalimetallcyanaten
Effenberger, Franz,Drauz, Karlheinz,Foerster, Siegfried,Mueller, Wolfgang
, p. 173 - 189 (2007/10/02)
α- and ω-halo- as well as α,ω-dihalocarboxylic alkyl esters react with potassium cyanate in the presence of alcohol at 80 - 120 deg C in dipolar aprotic solvents to yield α- and ω-(alkoxycarbonylamino)- and α,ω-bis(alkoxycarbonylamino)carboxylic alkyl esters, respectively, in good yields.Hydrolytic cleavage of these mono- or diurethanes with an aqueous solution of hydrochloric acid/formic acid leads to the corresponding amino acid hydrochlorides in nearly quantitative yields.
