2- beta -SUBSTITUTED-6-ALKYLIDENE PENICILLANIC ACID DERIVATIVES AS beta -LACTAMASE INHIBITORS

摘要

Compounds of formula (I), wherein R<1> and R<2> are each independently hydrogen, (C1-C10)alkyl, (C3-C8)cycloalkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, -COORa, -CONRbRc, cyano, -C(=O)Rd, -ORe, aryl, heteroaryl, oxazolidinyl, isoxazolidinyl, morpholinyl, -S(O)mRf, -NRgRh, azido, or halo; R<3> is (C3-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C1-C10)alkanoyl, (C3-C8)cycloalkyl, aryl, heteroaryl, aryl(C1-C10)alkyl, heteroaryl(C1-C10)alkyl, or -CH2Ri, wherein Ri is halo, cyano, cyanato, -ORj, -NRkRl, azido, -SRm, or (C3-C8)cycloalkyl; R<4> is hydrogen, (C1-C10)alkyl, (C3-C8)cycloalkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, aryl, or heteroaryl; m and n are each independently 0, 1, or 2; and their pharmaceutically acceptable salts, are useful for inhibiting beta -lactamase enzymes, for enhancing the activity of beta -lactam antibiotics, and for treating beta -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).