Masterson Luke A, Spanswick Victoria J, Hartley John A, Begent Richard H, Howard Philip W, Thurston David E
CR-UK Gene Targeting Drug Design Research Group, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1 1AX, UK.
Bioorg Med Chem Lett. 2006 Jan 15;16(2):252-6. doi: 10.1016/j.bmcl.2005.10.017. Epub 2005 Nov 15.
The design, synthesis and evaluation of four novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) prodrugs (1a,b and 2a,b; ) for potential use in carboxypeptidase G2 (CPG2)-based antibody-directed enzyme prodrug therapy (ADEPT) is reported. Although all four prodrugs were shown to be less cytotoxic than the released parent PBDs 3 and 4, the urea prodrugs 1b and 2b were found to be too unstable for use in ADEPT, whereas carbamates 1a and 2a are both stable in an aqueous environment and are good substrates for CPG2.
报道了四种新型吡咯并[2,1 - c][1,4]苯并二氮杂卓（PBD）前药（1a、b和2a、b）的设计、合成及评估，其有望用于基于羧肽酶G2（CPG2）的抗体导向酶前药疗法（ADEPT）。尽管所有四种前药的细胞毒性均低于释放出的母体PBDs 3和4，但发现脲前药1b和2b在ADEPT中使用时稳定性太差，而氨基甲酸酯1a和2a在水性环境中均稳定，且是CPG2的良好底物。
