Abstract: The following invention deals with the design, preparation, evaluation, and use of carbapenem antibiotics with improved activity, relative to current commercially available carbapenem antibiotics, against infections involving multidrug resistant, carbapenemase-producing Acinetobacter baumannii. The new carbapenem antibiotics are demonstrated to possess not only inherent antimicrobial activity, but also the ability to inhibit OXA-23, the most commonly produced serine carbapenemase in this species. This unusual carbapenemase-inhibitory activity also indicates that the compounds may be used synergistically, in combination with current commercial carbapenem antibiotics, to inhibit key class D carbapenemases, such as OXA-23. Additionally, one of the newly reported carbapenems is active against metallo-beta-lactamase producing A. baumannii. This is the first report of a metallo-beta-lactamase stable carbapenem antibiotic.

Abstract: Compounds of formula I: See Formula I in Figures Section wherein R1, R2, R3, R4 and n have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting simultaneously serine and metallo-?-lactamase enzymes, for enhancing the activity of ?-lactam antibiotics, and for treating ?-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula I, and novel intermediates useful for the synthesis of compounds of formula I.

Abstract: The invention provides compounds of formula (I): wherein: R1—R4 and A have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting ?-lactamase enzymes, for enhancing the activity of ?-lactam antibiotics, and for treating ?-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula (I), and intermediates useful for the synthesis of compounds of formula (I).