Application In Synthesis of 1,2,3-Trifluoro-4-methoxybenzeneOn November 2, 2006 ,《Discovery of [4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5-yl](2,3-difluoro-6- methoxyphenyl)methanone (R547), A Potent and Selective Cyclin-Dependent Kinase Inhibitor with Significant in Vivo Antitumor Activity》 appeared in Journal of Medicinal Chemistry. The author of the article were Chu, Xin-Jie; DePinto, Wanda; Bartkovitz, David; So, Sung-Sau; Vu, Binh T.; Packman, Kathryn; Lukacs, Christine; Ding, Qingjie; Jiang, Nan; Wang, Ka; Goelzer, Petra; Yin, Xuefeng; Smith, Melissa A.; Higgins, Brian X.; Chen, Yingsi; Xiang, Qing; Moliterni, John; Kaplan, Gerald; Graves, Bradford; Lovey, Allen; Fotouhi, Nader. The article conveys some information:
The cyclin-dependent kinases (CDKs) and their cyclin partners are key regulators of the cell cycle. Since deregulation of CDKs is found with high frequency in many human cancer cells, pharmacol. inhibition of CDKs with small mols. has the potential to provide an effective strategy for the treatment of cancer. The 2,4-diamino-5-ketopyrimidines 6 reported here represent a novel class of potent and ATP-competitive inhibitors that selectively target the cyclin-dependent kinase family. This diaminopyrimidine core with a substituted 4-piperidine moiety on the C2-amino position and 2-methoxybenzoyl at the C5 position has been identified as the critical structure responsible for the CDK inhibitory activity. Further optimization has led to a good number of analogs that show potent inhibitory activities against CDK1, CDK2, and CDK4 but are inactive against a large panel of serine/threonine and tyrosine kinases (Ki > 10 μM). As one of these representative analogs, compound 39 (I; R547) has the best CDK inhibitory activities (Ki = 0.001, 0.003, and 0.001 μM for CDK1, CDK2, and CDK4, resp.) and excellent in vitro cellular potency, inhibiting the growth of various human tumor cell lines including an HCT116 cell line (IC50 = 0.08 μM). An X-ray crystal structure of 39 bound to CDK2 has been determined in this study, revealing a binding mode that is consistent with our SAR. Compound 39 demonstrates significant in vivo efficacy in the HCT116 human colorectal tumor xenograft model in nude mice with up to 95% tumor growth inhibition. On the basis of its superior overall profile, 39 was chosen for further evaluation and has progressed into Phase I clin. trial for the treatment of cancer. In the experimental materials used by the author, we found 1,2,3-Trifluoro-4-methoxybenzene(cas: 203245-16-3Application In Synthesis of 1,2,3-Trifluoro-4-methoxybenzene)
1,2,3-Trifluoro-4-methoxybenzene(cas: 203245-16-3) is a member of aromaticfluorinated building blocks. Depending on which substituents are present, fluoroaromatic intermediates can be converted into fluorinated or fluorine-free commercial end products.Fluorine-containing aromatics have been incorporated into drugs (hypnotics, tranquilizers, antiinflammatory agents, analgesics, antibacterials).Application In Synthesis of 1,2,3-Trifluoro-4-methoxybenzene
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