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Synthesis and Microbiological Evaluation of Novel Tetracyclic Fluoroquinolones
Author(s) -
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 ToniJo,
Melnick Michael J.,
Gaston Ricky D.,
Moser Heinz E.
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700426
Subject(s) - pyrrolidine , ring (chemistry) , chemistry , amine gas treating , stereochemistry , combinatorial chemistry , potency , gram , bacteria , organic chemistry , biochemistry , in vitro , biology , genetics
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.