title: Application of the Stille coupling reaction to the synthesis of C2-substituted endo-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs).
abstract: The Stille coupling reaction has been used to introduce novel vinyl, alkynyl and heterocyclic substituents to the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine dilactams. Sodium borohydride reduction followed by N10-SEM deprotection has provided five analogues (6b, 8a-d) that contain C2-endo/exo-unsaturation and novel C2-substituents. These analogues have significant multilog cytotoxicity profiles in the NCI 60-Cell Line screen, and provide new SAR data for the PBD family.
authors.affiliation: Cancer Research UK Gene Targeted Drug Design Research Group, Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Arnaud C
authors.initials: AC
authors.lastname: Tiberghien
authors.forename: David
authors.initials: D
authors.lastname: Hagan
authors.forename: Philip W
authors.initials: PW
authors.lastname: Howard
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000480:Alkynes; D011758:Pyrroles; D014753:Vinyl Compounds; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines