2. Academic Validation
  3. Synthesis of a novel C2/C2'-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate

Synthesis of a novel C2/C2'-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate

  • Bioorg Med Chem Lett. 2009 Nov 15;19(22):6463-6. doi: 10.1016/j.bmcl.2009.09.012.
Philip W Howard 1,  Zhizhi Chen,  Stephen J Gregson,  Luke A Masterson,  Arnaud C Tiberghien,  Nectaroula Cooper,  Min Fang,  Marissa J Coffils,  Sarah Klee,  John A Hartley,  David E Thurston
Affiliations

Affiliation

  • 1 Spirogen Ltd, The School of Pharmacy, 29-39 Brunswick Square, London WC1N1AX, UK. philip.howard@spirogen.com
PMID: 19811912 DOI: 10.1016/j.bmcl.2009.09.012
Abstract

A prodrug form (17) of a novel C2/C2'-aryl-substituted pyrrolobenzodiazepine (PBD) dimer (16) has been synthesized by introducing sodium bisulfite groups to the C11/C11'-positions of the parent bis-imine. The prodrug form is highly water soluble, stable in aqueous conditions, and the rate of DNA cross-link formation is much slower compared to the parent bis-imine.

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