ChemMedChem p. 1687 - 1692 (2017)
Update date:2022-07-30
Topics:
Wagman, Allan S.
Cirz, Ryan
McEnroe, Glenn
Aggen, James
Linsell, Martin S.
Goldblum, Adam A.
Lopez, Sara
Gomez, Marcela
Miller, George
Simons, Lloyd J.
Belliotti, Thomas R.
Harris, Christina R.
Poel, Toni-Jo
Melnick, Michael J.
Gaston, Ricky D.
Moser, Heinz E.
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.
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