2. Academic Validation
  3. Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer

Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer

  • Bioorg Med Chem Lett. 2001 Nov 5;11(21):2859-62. doi: 10.1016/s0960-894x(01)00560-1.
S J Gregson 1,  P W Howard,  K E Corcoran,  T C Jenkins,  L R Kelland,  D E Thurston
Affiliations

Affiliation

  • 1 CRC Gene Targeted Drug Design Research Group, Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
PMID: 11597416 DOI: 10.1016/s0960-894x(01)00560-1
Abstract

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 efficient route, thus establishing that C2-C3-endo unsaturation enhances both cytotoxicity and DNA-binding affinity in A-Ring-linked PBD dimers but to a lesser extent than C2/C2'-exo-unsaturation. This new route has allowed the preparation of multi-gram quantities of the related clinical candidate 1 and should lead to more structurally diverse PBD dimer analogues.

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