Sj. Gregson et al., Synthesis of the first example of a C2-C3/C2 '-C3 '-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer, BIOORG MED, 11(21), 2001, pp. 2859-2862
We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1
-c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficie
nt route, thus establishing that C2-C3-endo unsaturation enhances both cyto
toxicity and DNA-binding affinity in A-Ring-linked PBD dimers but to a less
er extent than C2/C2'-exo-unsaturation. This new route has allowed the prep
aration of multi-gram quantities of the related clinical candidate 1 and sh
ould lead to more structurally diverse PBD dimer analogues. (C) 2001 Elsevi
er Science Ltd. All rights reserved.