title: Synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) C8 cyclic amine conjugates.
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.
authors.affiliation: Cancer Research UK Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1 1AX, UK.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Masterson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Croker
authors.forename: Terence C
authors.initials: TC
authors.lastname: Jenkins
authors.forename: Philip W
authors.initials: PW
authors.lastname: Howard
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D000588:Amines / Q000737:chemistry*; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003500:Cyclization; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000588:Amines; D011758:Pyrroles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D004247:DNA