3-Acylamino-1-carboxymethylaminocarbonyl-2-azetidinones

Claim 1

A compound having the formula ##STR58## or a pharmaceutically acceptable ester or salt thereof, wherein Z 1 is oxygen or sulfur; R 1 is an acyl group derived from a carboxylic acid; R 2 is hydrogen or methoxy; R 3 and R 4 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 3 and R 4 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxy, --CH 2 X 1 , --S--X 2 , --O--X 2 , ##STR59## wherein X 1 is azido, amino, hydroxy, carboxy, alkoxycarbonyl, alkanoylamino, phenylcarbonylamino, (substituted phenyl)carbonylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, cyano, --S--X 2 or --O--X 2 ; X 2 is alkyl, phenyl, or substituted phenyl; one of X 3 and X 4 is hydrogen and the other is hydrogen or alkyl, or X 3 and X 4 when taken together with the carbon atom to which they are attached form a cycloalkyl group; X 5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxy, alkoxycarbonyl, aminocarbonyl, (substituted amino)carbonyl, or cyano; A is --CH═CH--, --(CH 2 ) n --, --CH 2 --O--, --CH 2 --NH--, --CH 2 --S--CH 2 -- or --CH 2 --O--CH 2 --; n is 0, 1 or 2; and X 6 and X 7 are the same or different and each is hydrogen, alkyl, phenyl or substituted phenyl, or X 6 is hydrogen and X 7 is amino, substituted amino, alkanoylamino or alkoxy, or X 6 and X 7 when taken together with the nitrogen atom to which they are attached form a 4, 5, or 6-membered nitrogen containing heterocycle; R 5 and R 6 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, phenyl, substituted phenyl, cycloalkyl or a 4, 5, 6 or 7-membered heterocycle, or R 5 and R 6 together with the carbon atom to which they are attached are cycloalkyl, or one of R 5 and R 6 is hydrogen and the other is halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, alkenyl, alkynyl, 2-phenylethenyl, 2-phenylethynyl, carboxy, --CH 2 --X 1 , or ##STR60## or R 6 is hydrogen and R 5 together with R 7 and the atoms to which they are attached form a 4, 5, or 6-membered nitrogen containing heterocycle; and R 7 is hydrogen, alkyl, phenyl, substituted phenyl, cycloalkyl, a 4, 5, 6 or 7-membered heterocycle, ##STR61## or --(CH 2 ) n --Z 3 wherein n is 2, 3 or 4 and Z 3 is azido, --NZ 5 Z 6 , halogen, hydroxy, ##STR62## alkanoyloxy, alkoxy, phenyloxy, (substituted phenyl)oxy, (a 4, 5, 6 or 7-membered heterocycle)--O--, mercapto, alkylthio, phenylthio, (substituted phenyl)thio, alkylsulfinyl, alkylsulfonyl, ##STR63## wherein Z 4 is oxygen, sulfur or ##STR64## Z 5 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, Z 6 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, alkanoyl, phenylcarbonyl, or (substituted phenyl)carbonyl, and Z 7 is hydrogen, alkyl, phenyl or substituted phenyl; wherein the terms "alkyl" and "alkoxy" refer to groups having 1 to 10 carbon atoms; the term "cycloalkyl" refers to groups having 3, 4, 5, 6 or 7 carbon atoms; the term "substituted alkyl" refers to alkyl groups substituted with one, or more, azido, amino, halogen, hydroxy, carboxy, cyano, alkoxycarbonyl, aminocarbonyl, alkanoyloxy, alkoxy, phenyloxy, (substituted phenyl)oxy, mercapto, alkylthio, phenylthio, (substituted phenyl)thio, alkylsulfinyl or alkylsulfonyl groups; the terms "alkanoyl", "alkenyl", and "alkynyl" refer to groups having 2 to 10 carbon atoms; 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, 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, groups; the term "heteroaryl" refers to pyridinyl, furanyl, pyrrolyl, thienyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, thiazolyl, thiadiazolyl, pyrimidinyl, oxazolyl, triazinyl, tetrazolyl or one of the above groups substituted with one, or more, 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, groups; the term "substituted amino" refers to a group having the formula --NZ 8 Z 9 wherein Z 8 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and Z 9 is alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, hydroxy, cyano, alkoxy, phenylalkoxy, or amino; the expression "a 4, 5, or 6-membered nitrogen containing heterocycle" refers to 1-pyrrolidinyl, Δ 3 -pyrrolin-1-yl, 1-azetidinyl, 1-piperidinyl, Δ 3 -piperidein-1-yl, Δ 4 -piperidein-1-yl, 3-oxazolidinyl, 3-thiazolidinyl, 1-imidazolidinyl, 4-thiomorpholinyl, 4-morpholinyl, 1-piperazinyl, 1-hexahydroopyrimidinyl, tetrahydro-2H-1,3-thiazin-3-yl, tetrahydro-2H-1,3-oxazin-3-yl, 3-thiazolidinyl,-1-oxide, 3-thiazolidinyl,1,1-dioxide, 4-thiomorpholinyl,1-oxide, 4-thiomorpholinyl,1,1-dioxide, tetrahydro-2H-1,3-thiazin-3-yl,1-oxide, tetrahydro-2H-1,3-thiazin-3-yl,1,1-dioxide, or one of the above groups substituted with one, or more, oxo, halogen, hydroxy, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylsulfonyl, phenyl, substituted phenyl, azido, carboxy, aminocarbonyl, OZ 10 , NHZ 10 , or SZ 10 groups where Z 10 is alkanoyl, aminocarbonyl, aminosulfonyl, phenylcarbonyl, (substituted phenyl)carbonyl, alkyl, substituted alkyl, phenyl or substituted phenyl.