Heteroaryl derivatives of monocyclic beta-lactam antibiotics

Compounds having the formula ##STR35## wherein R.sub.1 and R.sub.2 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, substituted phenyl or a 4, 5, 6 or 7-membered heterocycle, or one of R.sub.1 and R.sub.2 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, phenylethyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 X.sub.1 ;

• wherein X.sub.1 is azido, amino, hydroxy, carboxyl, alkoxycarbonyl, alkanoylamino, phenylcarbonylamino, (substituted phenyl)carbonylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, cyano, ##STR36## --S--X.sub.2, or --O--X.sub.2 wherein A, X.sub.2, X.sub.6 and X.sub.7 are as hereinafter defined;
• --S--X.sub.2 or --O--X.sub.2 ;
• wherein X.sub.2 is alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, formyl, alkanoyl, substituted alkanoyl, phenylalkanoyl, substituted phenylalkanoyl, phenylcarbonyl, substituted phenylcarbonyl, heteroaryl, heteroarylalkyl, heteroarylalkanoyl or heteroarylcarbonyl, and in the case of when X.sub.1 is --O--X.sub.2 then X.sub.2 can also be alkylideneamino, alkanoylamino, carboxyalkylideneamino, alkylsulphinylamino, alkoxycarbonyl or alkylsulphonylamino;
• and R.sub.1 and R.sub.2 can also be ##STR37## wherein one of X.sub.3 and X.sub.4 is hydrogen and the other is hydrogen or alkyl, or X.sub.3 and X.sub.4 when taken together with the carbon atom to which they are attached form a cycloalkyl group;
• and X.sub.5 is formyl, alkanoyl, phenylcarbonyl, substituted phenylcarbonyl, phenylalkylcarbonyl, substituted phenylalkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, substituted aminocarbonyl, or cyano;
• or ##STR38## wherein A is --CH.dbd.CH--, --(CH.sub.2).sub.m --, --(CH.sub.2).sub.m --O--, --(CH.sub.2).sub.m --NH--, or --CH.sub.2 --S--CH.sub.2 --, where m is 0, 1 or 2, and X.sub.6 and X.sub.7 are the same or different and each is hydrogen, alkyl, phenyl or substituted phenyl, or X.sub.6 is hydrogen an X.sub.7 is amino, substituted amino, alkanoylamino or alkoxy, or X.sub.6 and X.sub.7 when taken together with the nitrogen atom to which they are attached form a 4, 5, 6 or 7-membered heterocycle;
• X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring;
• M is hydrogen or a cation capable of forming a pharmaceutically acceptable salt;
• the term "substituted phenyl" refers to a phenyl group substituted with 1, 2 or 3 amino, halogen, hydroxyl, trifluoromethyl, alkyl (of 1 to 4 carbon atoms), alkoxy (of 1 to 4 carbon atoms), alkanoyloxy, aminocarbonyl, or carboxy groups;
• the term "a 4, 5, 6 or 7-membered heterocycle" refers to pyridinyl, furanyl, pyrrolyl, thienyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, thiazolyl, thiadiazolyl, pyrimidinyl, oxazolyl, triazinyl, tetrazolyl, azetidinyl, oxetanyl, thietanyl, piperidinyl, piperazinyl, imidazolidinyl, oxazolidinyl, pyrrolidinyl, tetrahydropyrimidinyl, dihydrothiazolyl or hexahydroazepinyl or one of the above groups substituted with one or more oxo, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylsulfonyl, phenyl, substituted phenyl, 2-furfurylideneamino, benzylideneamino, or substituted alkyl wherein the alkyl group has 1 to 4 carbon atoms;
• the term "substituted amino" refers to a group having the formula --NX.sub.8 X.sub.9 wherein X.sub.8 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, and X.sub.9 is alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, hydroxy, cyano, alkoxy, phenylalkoxy or amino.