Synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) C8 cyclic amine conjugates

Luke A Masterson; Stephen J Croker; Terence C Jenkins; Philip W Howard; David E Thurston

doi:10.1016/j.bmcl.2003.12.017

Synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) C8 cyclic amine conjugates

Bioorg Med Chem Lett. 2004 Feb 23;14(4):901-4. doi: 10.1016/j.bmcl.2003.12.017.

Authors

Luke A Masterson¹, Stephen J Croker, Terence C Jenkins, Philip W Howard, David E Thurston

Affiliation

¹ Cancer Research UK Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1 1AX, UK.

PMID: 15012990
DOI: 10.1016/j.bmcl.2003.12.017

Abstract

We report examples of a series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogues 12-15 prepared from a common functionalized building block 11 that can be conveniently synthesized on a large scale and in optically pure form. Isoindoline analogue 15 is the most cytotoxic agent in this series, has the highest DNA-binding affinity, and shows significant activity in the in vivo hollow fibre assay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemistry*
Benzodiazepines* / chemical synthesis*
Benzodiazepines* / chemistry*
Benzodiazepines* / pharmacology*
Cell Division / drug effects
Cell Line, Tumor
Cyclization
DNA / drug effects
DNA / metabolism
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Pyrroles* / chemistry*
Pyrroles* / pharmacology*

Substances

Amines
Pyrroles
pyrrolo(2,1-c)(1,4)benzodiazepine
Benzodiazepines
DNA