Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy

Masterson, L.A., Spanswick, V.J., Hartley, J.A., Begent, R.H., Howard, P.W. and Thurston, D.E. (2006) Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy. Bioorganic and Medicinal Chemistry Letters, 16 (2). pp. 252-256. 10.1016/j.bmcl.2005.10.017.

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DOI: 10.1016/j.bmcl.2005.10.017

Abstract

The design, synthesis and evaluation of four novel pyrrolo[2,1-c][1,4] benzodiazepine (PBD) prodrugs (1a,b and 2a,b; Fig. 1) 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.

Item Type:Article
Uncontrolled Keywords:ADEPT; CPG2; PBD; Prodrug; Pyrrolo[2,1-c][1,4]benzodiazepines
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2904
Journal or Publication Title:Bioorganic and Medicinal Chemistry Letters
Deposited By:Library Staff
Deposited On:08 Mar 2012 10:27
Last Modified:08 Mar 2012 10:27

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