959795-77-8Relevant academic research and scientific papers
DERIVATIVES OF 4-(IMIDAZO[L,2-A]PYRIDIN-3-YL)-N-(PYRIDINYL)PYRIMIDIN- 2-AMINE AS THERAPEUTIC AGENTS
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Paragraph 0083; 0089; 00137; 00140, (2021/01/29)
A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of FLT3 and its mutant forms and/or other protein kinases such as CDKs. The compounds have the general structure I:
Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin-dependent kinases 4 and 6 as anticancer agents
Tadesse, Solomon,Bantie, Laychiluh,Tomusange, Khamis,Yu, Mingfeng,Islam, Saiful,Bykovska, Nataliya,Noll, Benjamin,Zhu, Ge,Li, Peng,Lam, Frankie,Kumarasiri, Malika,Milne, Robert,Wang, Shudong
, p. 2399 - 2413 (2018/05/14)
Background and Purpose: Cyclin D-dependent kinases 4 and 6 (CDK4/6) are crucial regulators of the G1 to S phase transition of the cell cycle and are actively pursued as therapeutic targets in cancer. We sought to discover a novel series of orally bioavailable and highly selective small molecule inhibitors of CDK4/6. Experimental Approach: The discovery of pharmacological inhibitors and optimization for potency, selectivity and drug properties were achieved by iterative chemical synthesis, biochemical screening against a panel of kinases, cell-based assays measuring cellular viability, cell cycle distribution, induction of apoptosis and the level of retinoblastoma tumour suppressor protein (Rb) phosphorylation and E2 factor (E2F)-regulated gene expression and in vitro biopharmaceutical and in vivo pharmacokinetic profiling. Key Results: We discovered several lead compounds that displayed >1000-fold selectivity for CDK4/6 over other members of the CDK family. The lead compounds, 82, 91 and 95, potently inhibited the growth of cancer cells by inducing G1 arrest with a concomitant reduction in the phosphorylation of Rb at S780 and in E2F-regulated gene expression. With a remarkable selectivity for CDK4 over 369 human protein kinases, 91 was identified as a highly potent and orally bioavailable drug candidate. Conclusions and Implications: We have identified unique and new inhibitors of CDK4/6 as potential drug candidates. Compound 91 represents an ideal candidate for further development as targeted cancer therapy.
Pyrimidine and pyrimidine dione CDK4/6 kinase inhibitors and uses thereof
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Paragraph 0075; 0076; 0077; 0078; 0095; 0096; 0097; 0098, (2018/07/30)
The invention belongs to the field of chemical medicine, relates to pyrimidine and pyrimidine dione CDK4/6 kinase inhibitor and its application, the pyrimidine and pyrimidine dione CDK4/6 kinase inhibitors of formula I shown in the compound or its pharmaceutically acceptable salt, and pharmaceutical compositions containing these compounds and these compounds or compositions of the pharmaceutical preparation in the application, the present invention provides a pyrimidine and pyrimidine dione compounds to CDK4 and CDK6 kinase has better inhibition activity, to breast cancer cell has significant inhibition function, can effectively reduce the incidence of tumor, extension of the tumor to the lives of patients,
2,4-dibasic miazines compound
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, (2017/08/29)
The invention belongs to the field of medical chemistry, relates to a 2,4-dibasic miazines compound and specifically relates to a compound shown as formula (I) or a pharmaceutically acceptable salt thereof, a drug compound thereof and an application thereof in treating EGFR or/and ALK mediated diseases.
Highly Potent, Selective, and Orally Bioavailable 4-Thiazol-N-(pyridin-2-yl)pyrimidin-2-amine Cyclin-Dependent Kinases 4 and 6 Inhibitors as Anticancer Drug Candidates: Design, Synthesis, and Evaluation
Tadesse, Solomon,Yu, Mingfeng,Mekonnen, Laychiluh B.,Lam, Frankie,Islam, Saiful,Tomusange, Khamis,Rahaman, Muhammed H.,Noll, Benjamin,Basnet, Sunita K. C.,Teo, Theodosia,Albrecht, Hugo,Milne, Robert,Wang, Shudong
, p. 1892 - 1915 (2017/03/17)
Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle and are validated targets for anticancer drug discovery. Herein we detail the discovery of a novel series of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as highly potent and selective inhibitors of CDK4 and CDK6. Medicinal chemistry optimization resulted in 83, an orally bioavailable inhibitor molecule with remarkable selectivity. Repeated oral administration of 83 caused marked inhibition of tumor growth in MV4-11 acute myeloid leukemia mouse xenografts without having a negative effect on body weight and showing any sign of clinical toxicity. The data merit 83 as a clinical development candidate.
N-(PYRIDIN-2-YL)-4-(THIAZOL-5-YL)PYRIMIDIN-2-AMINE DERIVATIVES AS THERAPEUTIC COMPOUNDS
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Paragraph 0092, (2017/02/28)
A novel class of inhibitors of protein kinases that are useful in the treatment of cell proliferative diseases and conditions, and especially those characterised by over-expression of CDK4, CDK6 and/or cyclin D, including certain cancers of lung, breast,
N- (HETERO)ARYL, 2- (HETERO)ARYL-SUBSTITUTED ACETAMIDES FOR USE AS WNT SIGNALING MODULATORS
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Page/Page column 56; 57, (2010/09/18)
The present invention relates to compounds of formulae 1 and 2 and methods for modulating the Wnt signaling pathway using these compounds, wherein A1, A2, B, Y and Z all represent rings.
Pyrrolopyrimidine Compounds and Their Uses
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Page/Page column 47, (2009/12/28)
The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.
