1178566-52-3Relevant articles and documents
Heterocyclic Compound as CDK-HDAC Double-Channel Inhibitor
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Paragraph 0125; 0127, (2022/02/27)
The invention provides compounds of formula (I) as shown below, including their possible enantiomers and diastereomers, as well as pharmaceutically acceptable salts, hydrates or solvates thereof. The invention also provides pharmaceutical compositions of
Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia
Yuan, Kai,Ji, Minghui,Xie, Shengnan,Qiu, Zhixia,Chen, Weijiao,Min, Wenjian,Xia, Fei,Zheng, Mingming,Wang, Xiao,Li, Jiaxing,Hou, Yi,Kuang, Wenbin,Wang, Liping,Gu, Wanjian,Li, Zhiyu,Yang, Peng
, p. 857 - 875 (2022/01/12)
Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51, which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo. In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclinical studies.
CDK6 inhibitor of pyrimidine benzo six-membered ring mother nucleus as well as preparation method and application of CDK6 inhibitor
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Paragraph 0048; 0059-0061, (2021/08/19)
The invention discloses a CDK6 inhibitor of a pyrimidine benzo six-membered ring mother nucleus and a preparation method and application of the CDK6 inhibitor, the compound structure of the CDK6 inhibitor is shown as a formula (C), and A is selected from O, C (O) or-NR1; R1 is selected from hydrogen or C1-C8 alkyl; B is selected from O or C; X is selected from C, C (O) or-NR2; R2 is selected from hydrogen or C1-C8 alkyl; Y is selected from C (O) or (CH2) n; n is 0 or 1; and Z is selected from hydrogen, C1-C8 alkyl or-C (O) OC1-C3. The invention also discloses a preparation method and application of the compound.