Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) alkylation subunit

  • Bioorg Med Chem. 2016 Oct 15;24(20):4779-4786. doi: 10.1016/j.bmc.2016.04.050.
Prem B Chanda  1 ,  Kristopher E Boyle  1 ,  Daniel M Brody  1 ,  Vyom Shukla  1 ,  Dale L Boger  2
Affiliations
  • 1. Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 2. Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: [email protected].
PMID: 27221071 DOI: 10.1016/j.bmc.2016.04.050
Abstract

The design, synthesis, and evaluation of methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) derivatives are detailed representing analogs of duocarmycin SA and yatakemycin containing an imidazole replacement for the fused pyrrole found in the DNA alkylation subunit.

Keywords
CC-1065; DNA alkylation; Duocarmycin; Yatakemycin.