69034-08-8Relevant articles and documents
Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile
Du, Wenxin,Hu, Xiaobei,Jin, Tingting,Kan, Weijuan,Li, Jia,Li, Kun,Liu, Tao,Wang, Chang,Wang, Peipei,Wu, Zhiqi,Xu, Lei,Zhang, Runyuan,Zhou, Yubo
supporting information, p. 15069 - 15090 (2021/11/13)
Checkpoint kinase 1 (CHK1) plays an important role in the DNA damage response pathway, being a potential anti-cancer drug target. In this study, we used a strategy for trifluoromethyl substitution to obtain orally bioavailable CHK1 inhibitors to overcome the limitations of lead compound 1, which can only be administered intravenously. After detailed investigation, we identified compound 6c as an oral CHK1 inhibitor, which demonstrated a considerably higher plasma exposure in mice. Compound 6c also showed good kinase selectivity. Moreover, it exhibited a significant antiproliferative effect in MV-4-11 cells singly and a synergistic effect in combination with gemcitabine in HT-29, A549, and RPMI-8226 cells. Additionally, compound 6c could inhibit tumor growth in the MV-4-11 xenograft mouse model. The combination of 6c and gemcitabine exhibited synergistic effect in the HT-29 xenograft mouse model. Thus, compound 6c was found to be a selective and oral potential anticancer CHK1 inhibitor.
2-polysubstituted aromatic ring-pyrimidine derivative and preparation and medical application
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Paragraph 0363; 0364; 0365; 0366, (2017/05/20)
The invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative, an optical isomer of the derivative or a medically acceptable salt or solvate of the derivative, and application of the compound, the optical isomer of the derivative or the medically acceptable salt or solvate of the derivative in preparing antineoplastic medicine. According to the 2-polysubstituted aromatic ring-pyrimidine derivative, by adopting N-substituted pyridine-2-minopyrimidine as a lead compound obtained based on virtual screening of a structure, a series of brand new small molecule Chk1 inhibitors are designed and synthesized, and a Chk1 kinase inhibitory activity test of a molecular level is conducted on the compound. Experiments prove that the compound is a Chk1 inhibitor with a strong antitumous effect, Chk1 kinase inhibitory activity and a prospect, and new cancer treating medicine, and can be used for treating solid tumor or leukemia related with human or animal cell proliferation. The 2-polysubstituted aromatic ring-pyrimidine derivative has a structure shown in the general formula I.
Trifluoromethylation of various aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide
Kino, Tatsuhito,Nagase, Yu,Ohtsuka, Yuhki,Yamamoto, Kyoko,Uraguchi, Daisuke,Tokuhisa, Kenji,Yamakawa, Tetsu
experimental part, p. 98 - 105 (2010/03/03)
Trifluoromethylation of aromatic and hetero-aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide was investigated. Various trifluoromethylated benzene derivatives, six-membered nitrogen-containing aromatic compounds and five-membered hetero-aromatic compounds were obtained under mild conditions. General orientation of electrophilic substitution of aromatic compounds was observed similarly as reported in other radical trifluoromethylation previously.
