945895-34-1Relevant academic research and scientific papers
Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2
Yu, Yu,Ran, Dongzhi,Jiang, Junhao,Pan, Tao,Dan, Yanrong,Tang,Li, Wei,Zhang, Lin,Gan, LinLing,Gan, Zongjie
, p. 2136 - 2140 (2019/07/03)
HDAC and CDK inhibitors have been demonstrated to be synergistically in suppressing cancer cell proliferation and inducing apoptosis. In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one molecule to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. The lead compound 6d, showing good HDAC1 and CDK2 inhibitory activity with IC50 values of 5.8 and 56 nM, respectively, exhibited attractive potency against several cancer cell lines in vitro. This work may lead to the discovery of a novel scaffold and potential dual HDAC/CDK inhibitors.
Discovery of N2-(4-Amino-cyclohexyl)-9-cyclopentyl- N6-(4-morpholin-4-ylmethyl-phenyl)- 9H-purine-2,6-diamine as a Potent FLT3 Kinase Inhibitor for Acute Myeloid Leukemia with FLT3 Mutations
Gucky, Tomá?,?ezní?ková, Eva,Rado?ová Muchová, Tereza,Jorda, Radek,Klejová, Zuzana,Malínková, Veronika,Berka, Karel,Bazgier, Václav,Ajani, Haresh,Lep?ík, Martin,Divoky, Vladimír,Kry?tof, Vladimír
, p. 3855 - 3869 (2018/05/14)
FLT3 tyrosine kinase is a potential drug target in acute myeloid leukemia (AML) because patients with FLT3-ITD mutations respond poorly to standard cytotoxic agents and there is a clear link between the disease and the oncogenic properties of FLT3. We present novel 2,6,9-trisubstituted purine derivatives with potent FLT3 inhibitory activity. The lead compound 7d displays nanomolar activity in biochemical assays and selectively blocks proliferation of AML cell lines harboring FLT3-ITD mutations, whereas other transformed and normal human cells are several orders of magnitude less sensitive. The MV4-11 cells treated with 7d suppressed the phosphorylation of FLT3 and its downstream signaling pathways, with subsequent G1 cell cycle arrest and apoptosis. Additionally, a single dose of 7d in mice with subcutaneous MV4-11 xenografts caused sustained inhibition of FLT3 and STAT5 phosphorylation over 48 h, in contrast to the shorter effect observed after administration of the reference FLT3 inhibitor quizartinib.
Synthesis and activity of 2,6,9-trisubstituted purines
Schow, Steven R.,Mackman, Richard L.,Blum, Cheri L.,Brooks, Eric,Horsma, Amy G.,Joly, Alison,Kerwar, Suresh S.,Lee, Gavin,Shiffman, Dov,Nelson, Marek G.,Wang, Xingbo,Wick, Michael M.,Zhang, Xiaoming,Lum, Robert T.
, p. 2697 - 2702 (2007/10/03)
The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented.
