148546-99-0Relevant articles and documents
Discovery of novel 4-azaaryl-N-phenylpyrimidin-2-amine derivatives as potent and selective FLT3 inhibitors for acute myeloid leukaemia with FLT3 mutations
Long, Yi,Yu, Mingfeng,Ochnik, Aleksandra M.,Karanjia, Jasmine D.,Basnet, Sunita KC.,Kebede, Alemwork A.,Kou, Lianmeng,Wang, Shudong
, (2021/02/03)
Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) is one of the most pursued targets in the treatment of acute myeloid leukaemia (AML) as its gene amplification and mutations, particularly internal tandem duplication (ITD), contribute to the pa
PYRIMIDINE COMPOUND, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF
-
Paragraph 0359; 0813; 0814; 0853; 0855; 0867, (2021/04/10)
The present invention discloses a pyrimidine compound, a preparation method thereof and a medical use thereof. Specifically, the present invention discloses a pyrimidine compound represented by formula (I), pharmaceutically acceptable salts thereof, a preparation method thereof, and a use thereof as a cyclin-dependent kinase 9 (CDK9) inhibitor, particularly for the treatment of cancer. The definition of each group in formula (I) is the same as that in the specification.
SAR study on: N 2, N 4-disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents
Jing, Liandong,Tang, Yanbo,Goto, Masuo,Lee, Kuo-Hsiung,Xiao, Zhiyan
, p. 11871 - 11885 (2018/04/12)
Cyclin-dependent kinases (CDKs) are pivotal kinases in cell cycle transition and gene transcription. A series of N2,N4-diphenylpyrimidine-2,4-diamines were previously identified as potent CDK2/CDK9 inhibitors. To explore the SAR of this structural prototype, twenty-four novel N2,N4-disubstituted pyrimidine-2,4-diamines were designed and synthesized. Among them, twenty-one compounds exhibited potent inhibitory activities against both CDK2/cyclin A and CDK9/cyclin T1 systems, and the most potent CDK2 and CDK9 inhibitors, 3g and 3c, showed IC50 values of 83 nM and 65 nM respectively. Most of these compounds displayed significant inhibition against the tested tumor cell lines in the SRB assay, and in particular, remained active against the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometer analysis of compounds 2a, 2d and 3b in MDA-MB-231 cells indicated that these compounds induced cell cycle arrest in G2/M phase. Docking studies on compound 3g were performed, which provided conducive clues for further molecular optimization.