Application of the Stille coupling reaction to the synthesis of C2-substituted endo-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs).
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.
Tiberghien
Arnaud C
AC
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.
Hagan
David
D
Howard
Philip W
PW
Thurston
David E
DE
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
D000480:Alkynes; D011758:Pyrroles; D014753:Vinyl Compounds; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines