Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones

  • Bioorg Med Chem Lett. 2011 Aug 1;21(15):4585-8. doi: 10.1016/j.bmcl.2011.05.112.
Kevin R Marks  1 ,  Muhammad Malik ,  Arkady Mustaev ,  Hiroshi Hiasa ,  Karl Drlica ,  Robert J Kerns
Affiliations
  • 1. Division of Medicinal and Natural Products Chemistry, University of Iowa College of Pharmacy, Iowa City, IA 52242, USA.
PMID: 21705218 DOI: 10.1016/j.bmcl.2011.05.112
Abstract

Novel fluoroquinolone derivatives substituted with a 2-thioalkyl moiety, with and without a concomitant 3-carboxylate group, were synthesized to evaluate the effect of C-2 thioalkyl substituents on gyrase binding and inhibition. The presence of a 2-thioalkyl group universally decreased activity as compared to parent fluoroquinolones. However, with derivatives of moxifloxacin the presence of either a 2-thioalkyl group or a 3-carboxylate moiety increased activity over the 2,3-unsubstituted derivative. Energy minimization of structures provides an explanation for relative activities of fluoroquinolones having a C-2 thio moiety.

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