362656-25-5Relevant articles and documents
PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES AS CDK INHIBITORS
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, (2021/09/17)
The pyrido[2,3-d]pyrimidin-7(8H)-ones of Formula (1) and pharmaceutical compositions containing compounds of Formula (1) as CDK inhibitors are disclosed herein. Methods and use of a compound of Formula 1 in the treatment of cancer and manufacture are also disclosed.
ANTI-PROLIFERATIVE AGENTS FOR TREATING PAH
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Page/Page column 104-105, (2020/10/28)
This invention relates to compounds of general Formula I in which A, R1, R2, R3 and R4 are as defined herein, and the pharmaceutically acceptable salts thereof; to pharmaceutical compositions comprising such compounds and salts; to methods of using such compounds, salts and compositions for treating pulmonary hypertension and related diseases, like pulmonary arterial hypertension; to methods of using such compounds, salts and compositions for treating abnormal cell growth, such as cancer; and to processes to make such compounds, salts and compositions.
Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4
VanderWel, Scott N.,Harvey, Patricia J.,McNamara, Dennis J.,Repine, Joseph T.,Keller, Paul R.,Quin III, John,Booth, R. John,Elliott, William L.,Dobrusin, Ellen M.,Fry, David W.,Toogood, Peter L.
, p. 2371 - 2387 (2007/10/03)
Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]-pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, and good potency against Cdks has been reported for representative examples. Obtaining selectivity for individual Cdk enzymes, particularly Cdk4, has been challenging. Here, we report that the introduction of a methyl substituent at the C-5 position of the pyrido[2,3-d]pvrimidin-7-one template is sufficient to confer excellent selectivity for Cdk4 vs other Cdks and representative tyrosine kinases. Further optimization led to the identification of highly potent and selective inhibitors of Cdk4 that exhibit potent antiproliferative activity against human tumor cells in vitro. The most selective Cdk4 inhibitors were evaluated for antitumor activity against MDA-MB-435 human breast carcinoma xenografts in mice.
