Marugan Juan Jose, Leonard Kristi, Raboisson Pierre, Gushue Joan M, Calvo Raul, Koblish Holly K, Lattanze Jennifer, Zhao Shuyuan, Cummings Maxwell D, Player Mark R, Schubert Carsten, Maroney Anna C, Lu Tianbao
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 665 Stockton Drive, Exton, PA 19341, USA.
Bioorg Med Chem Lett. 2006 Jun 15;16(12):3115-20. doi: 10.1016/j.bmcl.2006.03.067. Epub 2006 Apr 21.
The 1,4-benzodiazepine-2,5-dione is a suitable template to disrupt the interaction between p53 and Hdm2. The development of an enantioselective synthesis disclosed the stereochemistry of the active enantiomer. An in vitro p53 peptide displacement assay identified active compounds. These activities were confirmed in several cell-based assays including induction of the p53 regulated gene (PIG-3) and caspase activity.
1,4-苯并二氮杂卓-2,5-二酮是破坏p53与Hdm2之间相互作用的合适模板。对映选择性合成的发展揭示了活性对映体的立体化学。体外p53肽置换试验鉴定出了活性化合物。这些活性在包括诱导p53调控基因（PIG-3）和半胱天冬酶活性在内的几种基于细胞的试验中得到了证实。
