Wang, Le; Sullivan, Gerard M.; Hexamer, Laura A.; Hasvold, Lisa A.; Thalji, Reema; Przytulinska, Magdalena; Tao, Zhi-Fu; Li, Gaoquan; Chen, Zehan; Xiao, Zhan; Gu, Wen-Zhen; Xue, John; Bui, Mai-Ha; Merta, Philip; Kovar, Peter; Bouska, Jennifer J.; Zhang, Haiying; Park, Chang; Stewart, Kent D.; Sham, Hing L.; Sowin, Thomas J.; Rosenberg, Saul H.; Lin, Nan-Horng published the artcile< Design, Synthesis, and Biological Activity of 5,10-Dihydro-dibenzo[b,e][1,4]diazepin-11-one-Based Potent and Selective Chk-1 Inhibitors>, Application In Synthesis of 22717-55-1, the main research area is benzodiazepinone preparation heterocyclization Suzuki coupling; check point kinase Chk1 inhibitor human; cancer anticancer structure activity pharmacokinetics.
A novel series of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones have been synthesized as potent and selective checkpoint kinase 1 (Chk1) inhibitors via structure-based design. Aided by protein X-ray crystallog., medicinal chem. efforts led to the identification of I, with potent enzymic activity against Chk1 kinase. While maintaining a low cytotoxicity of its own, I exhibited a strong ability to abrogate G2 arrest and increased the cytotoxicity of camptothecin by 19-fold against SW620 cells. Pharmacokinetic studies revealed that it had a moderate bioavailability of 20% in mice. Two important binding interactions between II and Chk1 kinase, revealed by X-ray cocrystal structure, were hydrogen bonds between the hinge region and the amide bond of the core structure and a hydrogen bond between the methoxy group and Lys38 of the protein.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 22717-55-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Application In Synthesis of 22717-55-1.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics