Nanomolar β-lactamase inhibitors

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S438000, C548S190000, C548S199000, C564S123000

Reexamination Certificate

active

10731738

ABSTRACT:
New carboxyphenyl-glycylboronic acid transition-state analog inhibitors, representative of a class of compounds effective against class C β-lactamase AmpC. The new compounds improve inhibition by over two-orders of magnitude compared to analogous glycylboronic acids, with Ki values as low as 1 nM.

REFERENCES:
patent: 4963655 (1990-10-01), Kinder et al.
Powers et al., “Structures of Ceftazidime and Its Transition-State Analogue in Complex with AmpC β-Lactamase: Implications for Resistance Mutations and Inhibitor Design,” Biochemistry, 40, 9207-9214, published on web Jul. 10, 2001.
Powers et al., “The complexed structure and antimicrobial activity of a non β-lactam inhibitor of AmpC β-lactamase,” Protein Science, 8, 2330-2337, published 1999.
Weston et al., “Structure-based enhancement of boronic acid-based inhibitors of AmpC β-lactamase,” J. Med. Chem., 41, 4577-4586, 1998.
Morandi et al., “Nanomolar Inhibitors of AmpC β-lactamase,” JACS, 125, 685-695, 2003.
Kinder, et al., “Acylamido boronic acids and difluoroborane analogs of amino acids,” J. Med. Chem., vol. 28, pp. 1917-1925, 1985.
Powers et al., “Structures of Ceftazidime and Its Transition-State Analogue in Complex with AmpC β-Lactamase: Implications for Resistance Mutations and Inhibitor Design,” Biochemistry, 40, 9207-9214, published on web Jul. 10, 2001.

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