ChemMedChem
ChemMedChem
5 years ago

Synthesis and Microbiological Evaluation of Novel Tetracyclic Fluoroquinolones

Synthesis and Microbiological Evaluation of Novel Tetracyclic Fluoroquinolones
Adam A. Goldblum, Glenn McEnroe, Allan S. Wagman, Heinz E. Moser, Thomas R. Belliotti, Lloyd J. Simons, Martin S. Linsell, Sara Lopez, Toni-Jo Poel, George Miller, Marcela Gomez, Michael J. Melnick, Christina R. Harris, Ricky D. Gaston, James Aggen, Ryan Cirz
Conformationally constrained tetracyclic fluoroquinolones (FQs) were synthesized and profiled for their microbiological spectrum. The installation of a seven-membered ring between the pyrrolidine substituents and the C8 position on the FQ core scaffold resulted in a remarkable enhancement of microbiological potency toward both Gram-positive and Gram-negative bacteria. Focused optimization of seven-membered ring composition, stereochemistry, and amine placement led to the discovery of the two lead compounds that were selected for further progression. Conformationally constrained tetracyclic fluoroquinolones (FQs) were synthesized and profiled for their microbiological spectrum. Installation of a seven-membered ring between the pyrrolidine substituents and the C8 position on the FQ scaffold resulted in a remarkable enhancement in potency on both Gram-positive and Gram-negative bacteria. Focused optimization of seven-membered ring composition, stereochemistry, and amine placement yielded the two lead compounds 36 and 40.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/cmdc.201700426

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.