Synthesis and Microbiological Evaluation of Novel Tetracyclic Fluoroquinolones
2017
Conformationally-constrained tetracyclic fluoroquinolones (FQs) were synthesized and profiled for their microbiological spectrum. The installation of a 7-membered ring between the pyrrolidine substituents and the C8-position on the FQ core scaffold resulted in a remarkable enhancement of microbiological potency on both Gram-positive and Gram-negative bacteria. Focused optimization of 7-membered ring composition, stereochemistry, and amine placement led to the discovery of the two lead compounds that were selected for further progression.
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