571188-59-5Relevant articles and documents
Copper-catalyzed selective C-N bond formation with 2-amino, 2-hydroxy and 2-bromo-5-halopyridine
Roy, Swarnali,Paul, Barnali,Mukherjee, Ayan,Kundu, Biswajit,Talukdar, Arindam
, p. 44366 - 44370 (2017)
A copper-catalyzed 1,2-diol amination at the electron-rich C-5 position of unprotected 2-amino/2-hydroxy-5-halopyridine provided excellent yields. Selective amination preferably at C-5 in 2-bromo-5-iodopyridine was achieved under the same conditions. The selective, generally mild and economical coupling reaction at C-5 position described herein could be achieved with amines, heterocycles and amides.
Selective and novel cyclin-dependent kinases 4 inhibitor: synthesis and biological evaluation
Guo, Qingxiang,Li, Yongtao,Zhang, Chao,Huang, Zhi,Wang, Xin,Nie, Yongwei,Li, Yao,Liu, Yanhua,Yang, Shengyong,Xiang, Rong,Fan, Yan
, p. 1666 - 1678 (2018)
A series of novel LEE011 derivatives containing pyridine N-oxide were designed, synthesized and evaluated. Systematic study of the structure-activity relationship (SAR) improves the selectivity for CDK4 and led to the identification of compound 9a. The compound showed comparable CDK4 kinase activity with ribociclib and greater selectivity over the closely related CDK6 kinase. The selective CDK4 inhibitor 9a has been demonstrated the antitumor activity via G1 phase cell cycle arrest, as well as dual CDK4/CDK6 inhibitor ribociclib and significantly down-regulated the activity of CDK4-cyclinD-Rb pathway of tumor cells. Taken together, this compound may act as promising lead compound for further development of new CDK4 inhibitors.
Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma
Yuan, Kai,Kuang, Wenbin,Chen, Weijiao,Ji, Minghui,Min, Wenjian,Zhu, Yasheng,Hou, Yi,Wang, Xiao,Li, Jiaxing,Wang, Liping,Yang, Peng
, (2021/12/09)
Multiple myeloma (MM) ranks second in malignant hematopoietic cancers, and the most common anti-MM drugs easily generate resistance. CDK4/6 have been validated to play determinant roles in MM, but no remarkable progress has been obtained from clinical trials of CDK4/6 inhibitors for MM. To discover novel CDK6 inhibitors with better potency and high druggability, structure-based virtual screening was conducted to identify compound 10. Further chemical optimization afforded a better derivative, compound 32, which exhibited strong inhibition of CDK4/6 and showed high selectivity over 360+ kinases, including homologous CDKs. The in vivo evaluation demonstrated that compound 32 possessed low toxicity (LD50 > 10,000 mg/kg), favorable bioavailability (F% = 51%), high metabolic stability (t1/2 > 24 h) and strong anti-MM potency. In summary, we discovered a novel CDK4/6 inhibitor bearing favorable drug-like properties and offered a great candidate for MM preclinical studies.
CDK6/DYRK2 Double-target inhibitor as well as preparation method and application thereof
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, (2021/02/24)
The present invention discloses a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. The invention also discloses a preparation method of the compound and application of the compound in prevention and/or treatment of cancers or tumor-related diseases, especially breast cancer, prostate cancer, lung cancer, multiple myeloma, leukemia, gastric cancer, ovarian cancer, colon cancer, liver cancer, pancreatic cancer, human glioma and other diseases. The compound provided by the invention is expected to be developed into a new generation of anti-cancer drugs.
Intermediate compound as well as preparation method and application thereof
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, (2021/07/24)
The invention discloses an intermediate compound as well as a preparation method and application thereof. The synthesized intermediate compound is used for preparing targeted anti-cancer drugs, such as CDK4, CDK6, DYRK2 and other inhibitors, and is used for preventing and/or treating cancers or tumor related diseases including breast cancer, prostate cancer, lung cancer, multiple myeloma, leukemia, gastric cancer, ovarian cancer, colon cancer, liver cancer, pancreatic cancer and human glioma. The intermediate compound is simple in preparation condition, high in reaction yield and stable in performance.
Anti-cancer quinoxaline pyrimidinamine heterocyclic compound as well as preparation method and application thereof
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, (2021/07/21)
The invention discloses an anti-cancer quinoxaline pyrimidinamine heterocyclic compound and a preparation method and application thereof, the structure of the compound is shown as a formula (S), and X is selected from C (O) or (CH2) n; n is 0 or 1; R1 is selected from hydrogen and C1-C8 alkyl; R2 is selected from hydrogen, C1-C8 alkyl, morpholine ring or-NR5R6, and R5 and R6 are selected from hydrogen and C1-C8 alkyl; R3 is selected from hydrogen, methoxyl and halogen; and R4 is selected from hydrogen, C1-C8 alkyl,-S (O) 2Me and-C (O) OC1-C3. The invention also discloses a preparation method and application of the compound.
Method for preparing 4 - (6 -aminopyridine -3 -yl) piperazine -1 - carboxylic acid tert-butyl ester
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Paragraph 0042; 0050-0054; 0062-0066; 0073-0076, (2021/09/26)
The invention discloses a method for preparing 4 - (6 - aminopyrid -3 -yl) piperazine -1 - carboxylic acid tert-butyl ester, which comprises the following steps of: reacting 2 - aminopyridine with iodine to generate 2 - amino -5 -iodopyridine. Step II: 2 - amino -5 -iodopyridine was subjected to a coupling reaction to obtain 4 - (6 - aminopyrid -3 -yl) piperazine -1 -carboxylic acid tert-butyl ester. The method has the advantages of short synthetic route, high target product yield and low cost.
HPK1 ANTAGONISTS AND USES THEREOF
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, (2021/03/19)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.
Azaindole pyrimidinamine heterocyclic compound as well as preparation method and application thereof
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, (2021/08/14)
The invention discloses an azaindole pyrimidinamine heterocyclic compound as well as a preparation method and application thereof. The compound is shown as a formula (S). The compound provided by the invention can inhibit malignant proliferation of cancers, has good treatment effect, low toxicity and good drug metabolism characteristics, is not easy to generate drug resistance, and can be used for preparing drugs for treating cancers or tumor-related diseases. The cancers or tumor-related diseases include multiple myeloma, leukemia, breast cancer, prostate cancer, lung cancer, liver cancer, gastric cancer, bone cancer, brain cancer, head and neck cancer, intestinal cancer, pancreatic cancer, bladder cancer, testicular cancer, ovarian cancer and endometrial cancer.
Discovery and in Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor
Chen, Xing,Yan, Yaoyao,Zhang, Zhaoyan,Zhang, Faming,Liu, Mingming,Du, Leran,Zhang, Haixia,Shen, Xiaobao,Zhao, Dahai,Shi, Jing Bo,Liu, Xinhua
, p. 11857 - 11885 (2021/09/02)
Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent "non-peptidyl non-covalent cathepsin C inhibitor"was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.
