US Patent:
20120149710, Jun 14, 2012
Inventors:
Michael E. Jung - Los Angeles CA, US
Robert T. Clubb - Culver City CA, US
Sung Wook Yi - Los Angeles CA, US
Nutee Suree - Lampang, TH
Jeremy Justin Clemens - San Diego CA, US
International Classification:
A61K 31/50
C07D 401/12
C07D 403/12
C07D 417/06
A61P 31/04
C07D 231/18
A61K 31/501
A61K 31/427
A61K 31/426
A61K 31/415
C07D 237/18
C07D 277/36
US Classification:
51425202, 544240, 544238, 548200, 548183, 5483701, 514247, 51425203, 514365, 514369, 514404
Abstract:
Bacterial infections, including Methicillin resistant (MRSA) infections are a major health problem that has created a pressing need for new antibiotics. Pyridazinone, rhodanine, and pyrazolethione compounds effective inhibit the enzymatic activity of sortase A (srtA) found in gram positive bacteria are disclosed. A structure activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with ICvalues in the sub-micromolar range. Compounds that inhibit the SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Many of these molecules also inhibit the sortase enzyme from suggesting that they may be generalized sortase inhibitors.The novel compounds, compositions, uses, formulations, medicaments, articles of manufacture provide improved materials, uses, and treatments useful in combating infectious disorders.
