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

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...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 14; no. 4; pp. 901 - 904
Main Authors Masterson, Luke A., Croker, Stephen J., Jenkins, Terence C., Howard, Philip W., Thurston, David E.
Format Journal Article
LanguageEnglish
Published Oxford Elsevier 23.02.2004
Subjects
Amines - chemistry
Antineoplastic agents
Benzodiazepines - chemical synthesis
Benzodiazepines - chemistry
Benzodiazepines - pharmacology
Biological and medical sciences
Cell Division - drug effects
Cell Line, Tumor
Cyclization
DNA - drug effects
DNA - metabolism
Drug Screening Assays, Antitumor
General aspects
Humans
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Pyrroles - chemistry
Pyrroles - pharmacology
Antineoplastic agent
Human
Angular nitrogen heterocycle
Lactam
Cytotoxicity
Tricyclic compound
In vitro
Isoindole derivatives
In vivo
Ovary
Biological fixation
Cell line
Structure activity relation
DNA
Hollow fiber
Conjugated compound
Chemical synthesis
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2003.12.017