A novel approach to the synthesis of cytotoxic C2-C3 unsaturated pyrrolo[2,1-c]benzodiazepines (PBDs) with conjugated acrylyl C2-substituents.
A concise synthesis of three novel C2-C3 unsaturated pyrrolo[2,1-c][1,4]benzodiazepine analogues (18-20) containing conjugated acrylyl C2-substituents is reported that utilises Heck coupling to install the C2-acrylyl side chains. These analogues possess significant cytotoxicity according to the NCI 60-cell line screen with 18 surpassing anthramycin (1) in potency.
Chen
Zhizhi
Z
Cancer Research UK Gene Targeted Drug Design Research Group, Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Gregson
Stephen J
SJ
Howard
Philip W
PW
Thurston
David E
DE
D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000633:toxicity*; D045744:Cell Line, Tumor; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis / Q000633:toxicity
D011758:Pyrroles; D001569:Benzodiazepines; C013231:pyrroline