1421693-22-2Relevant articles and documents
A method for preparing such CDK inhibitors (by machine translation)
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, (2017/10/05)
The invention discloses a method for preparing such CDK inhibitors, will be single-methyl thiourea and 1 - N monochloride reaction, 4 - dimethylthiazole - 2 - amine, by bromo reaction to obtain 5 - bromo - N, 4 - dimethylthiazole - 2 - amine, under the action of the catalyst after the with the borate to obtain aromatic borate intermediates; aromatic borate ester intermediate with 2, 4 - dichloro - 5 fluoro uracil in the noble metal catalytic under suzuki coupling reaction to obtain the coupling product to continue after the Buchwald - Hartwig with the aromatic amine in the reaction, ultimately to obtain the target product. (by machine translation)
THERAPEUTIC COMPOUNDS
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Paragraph 0187; 0188, (2015/04/21)
The present invention relates to compounds of formula (I): wherein R1 is NH2 or NHMe; R2 is halo; and one of R3 or R4 is hydrogen and the other is selected from —SO2NH2, —SO2NHMe or —SO2NMe2, —SO2NHEt, or —SO2NEt2; or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula (I) are inhibitors of protein kinases, especially cyclic dependent kinases (CDKs) such as CDK9. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which protein kinase/CDK activity is implicated.
THERAPEUTIC COMPOUNDS
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Paragraph 00168, (2013/11/05)
The present invention relates to compounds of formula (I): wherein R1 is NH2 or NHMe; R2 is halo; and one of R3 or R4 is hydrogen and the other is selected from –SO2NH2, -SO2NHMe or –SO2NMe2, -SO2NHEt, or -SO2NEt2; or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula (I) are inhibitors of protein kinases, especially cyclic dependent kinases (CDKs) such as CDK9. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which protein kinase/CDK activity is implicated.
Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: Synthesis, X-ray crystal structures, structure-activity relationship, and anticancer activities
Shao, Hao,Shi, Shenhua,Huang, Shiliang,Hole, Alison J.,Abbas, Abdullahi Y.,Baumli, Sonja,Liu, Xiangrui,Lam, Frankie,Foley, David W.,Fischer, Peter M.,Noble, Martin,Endicott, Jane A.,Pepper, Chris,Wang, Shudong
, p. 640 - 659 (2013/03/28)
Cancer cells often have a high demand for antiapoptotic proteins in order to resist programmed cell death. CDK9 inhibition selectively targets survival proteins and reinstates apoptosis in cancer cells. We designed a series of 4-thiazol-2-anilinopyrimidine derivatives with functional groups attached to the C5-position of the pyrimidine or to the C4-thiazol moiety and investigated their effects on CDK9 potency and selectivity. One of the most selective compounds, 12u inhibits CDK9 with IC50 = 7 nM and shows over 80-fold selectivity for CDK9 versus CDK2. X-ray crystal structures of 12u bound to CDK9 and CDK2 provide insights into the binding modes. This work, together with crystal structures of selected inhibitors in complex with both enzymes described in a companion paper,(34) provides a rationale for the observed SAR. 12u demonstrates potent anticancer activity against primary chronic lymphocytic leukemia cells with a therapeutic window 31- and 107-fold over those of normal B- and T-cells.