1356962-87-2Relevant academic research and scientific papers
AMINOPYRIMIDINE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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Paragraph 187; 224, (2021/12/12)
Provided herein are novel compounds, for example, compounds having a Formula (I) or Formula (II), or a pharmaceutically acceptable salt thereof. Also provided herein are methods of preparing the compounds and methods of using the compounds, for example, for treating various cancer described herein, such as lung cancer (e.g., non-small cell lung cancer).
Selective Covalent Targeting of Mutated EGFR(T790M) with Chlorofluoroacetamide-Pyrimidines
Fuchida, Hirokazu,Hosokawa, Keitaro,Inamori, Ryo,Koyanagi, Satoru,Kuwata, Keiko,Matsunaga, Naoya,Ohdo, Shigehiro,Ojida, Akio,Ono, Mayumi,Sato, Mami,Shibata, Tomohiro,Shindo, Naoya,Tokunaga, Keisuke,Watari, Kosuke,Xiao-Lin, Guo
supporting information, p. 1137 - 1144 (2020/07/04)
Covalent modification of disease-associated proteins with small molecules is a powerful approach for achieving an increased and sustained pharmacological effect. To reduce the potential risk of nonselective covalent modification, molecular design of covalent inhibitors is critically important. We report herein the development of a targeted covalent inhibitor for mutated epidermal growth factor receptor (EGFR) (L858R/T790M) using α-chlorofluoroacetamide (CFA) as the reactive group. The chemically tuned weak reactivity of CFA was suitable for the design of third-generation EGFR inhibitors that possess the pyrimidine scaffold. The structure-activity relationship study revealed that CFA inhibitor 18 (NSP-037) possessed higher inhibition selectivity to the mutated EGFR over wild-type EGFR when compared to clinically approved osimertinib. Mass-based chemical proteomics analyses further revealed that 18 displayed high covalent modification selectivity for the mutated EGFR in living cells. These findings highlight the utility of CFA as a warhead of targeted covalent inhibitors and the potential application of the CFA-pyrimidines for treatment of non-small-cell lung cancer.
INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7)
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Paragraph 169, (2018/02/28)
The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
CHEMICAL COMPOUNDS
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Page/Page column 24; 25, (2012/02/06)
The present invention relates to compounds of Formula (I) and/or Formula (Ia): and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds inhibit ALK kinase activity, and thus may be used for the tr
