Claims
- 1. A .beta.-lactam having the formula ##STR53## or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is an acyl group derived from a carboxylic acid;
- R.sub.2 is hydrogen or methoxy;
- R.sub.3 and R.sub.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.sub.3 and R.sub.4 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 --X.sub.1, --S--X.sub.2, --O--X.sub.2, ##STR54## R.sub.5 and R.sub.6 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, phenyl, subtituted phenyl, cycloalkyl or a 4, 5, 6 or 7-membered heterocycle, or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached are cycloalkyl or a 4, 5, 6 or 7-membered heterocycle, or one of R.sub.5 and R.sub.6 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 --X.sub.1, --S--X.sub.2, --O--X.sub.2 or ##STR55## X.sub.1 is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, cyano, --S--X.sub.2 or --O--X.sub.2 ;
- X.sub.2 is alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, alkanoyl, substituted alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl or heteroarylcarbonyl;
- 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;
- X.sub.5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)carbonyl, or cyano;
- A is --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --(CH.sub.2).sub.n --, --(CH.sub.2).sub.n' --O--, --(CH.sub.2).sub.n' --NH--, --(CH.sub.2).sub.n' --S--CH.sub.2 --;
- n is 0, 1, 2 or 3;
- n' is 1 or 2; and
- X.sub.6 and X.sub.7 are the same or different and each is hydrogen or alkyl, or X.sub.6 is hydrogen and X.sub.7 is amino, substituted amino, acylamino or alkoxy;
- wherein the terms "alkyl" and "alkoxy" refer to groups having 1 to 10 carbon atoms;
- the term "cycloalkyl" refers to cycloalkyl 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 alkanoyl" refers to a group having the formula (substituted alkyl) ##STR56## or phenylalkanoyl; 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) or carboxyl groups;
- the term "substituted amino" refers to a group having the formula --NY.sub.1 Y.sub.2 wherein Y.sub.1 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, and Y.sub.2 is alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, hydroxy, cyano, alkoxy, phenylalkoxy or amino;
- 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-furylmethyleneamino, phenylmethyleneamino, substituted alkyl, wherein the alkyl group has 1 to 4 carbon atoms, 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, azetinyl, 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-furylmethyleneamino, phenylmethyleneamino or substituted alkyl, wherein the alkyl group has 1 to 4 carbon atoms, groups.
- 2. A .beta.-lactam in accordance with claim 1, a salt of [3S-[3.alpha.(Z),4.alpha.]]-[[3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinyl]oxy]methanesulfonic acid.
- 3. A .beta.-lactam in accordance with claim 1, a salt of [3S-[3.alpha.,(Z)4.alpha.]]-2-[[[1-(2-amino-4-thiazolyl)-2-[[4-methyl-2-oxo-1-(sulfomethoxy)-3-azetidinyl]-amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid.
- 4. A .beta.-lactam in accordance with claim 1 wherein R.sub.2 is hydrogen.
- 5. A .beta.-lactam in accordance with claim 4 wherein R.sub.3 and R.sub.4 are each hydrogen.
- 6. A .beta.-lactam in accordance with claim 4 wherein R.sub.3 is hydrogen and R.sub.4 is methyl.
- 7. A .beta.-lactam in accordance with claim 4 wherein R.sub.3 is methyl and R.sub.4 is hydrogen.
- 8. A .beta.-lactam in accordance with claim 4 wherein R.sub.5 and R.sub.6 are each hydrogen.
- 9. A .beta.-lactam in accordance with claim 4 wherein R.sub.5 and R.sub.6 are each methyl.
- 10. A .beta.-lactam in accordance with claim 4 wherein R.sub.1 is (Z)-2-amino-.alpha.-[(1-carboxy-1-methylethoxy)imino]-4-thiazoleacetyl.
- 11. A .beta.-lactam in accordance with claim 1 wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are each hydrogen.
- 12. A .beta.-lactam in accordance with claim 1 wherein R.sub.2, R.sub.3, R.sub.5 and R.sub.6 are each hydrogen and R.sub.4 is methyl.
- 13. A .beta.-lactam in accordance with claim 1 wherein R.sub.2, R.sub.4, R.sub.5 and R.sub.6 are each hydrogen and R.sub.3 is methyl.
- 14. A .beta.-lactam having the formula ##STR57## or a salt thereof, wherein R.sub.3 and R.sub.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.sub.3 and R.sub.4 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 X.sub.1, --S--X.sub.2, --O--X.sub.2, ##STR58## R.sub.5 and R.sub.6 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, phenyl, subtituted phenyl, cycloalkyl or a 4, 5, 6 or 7-membered heterocycle, or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached are cycloalkyl or a 4, 5, 6 or 7-membered heterocycle, or one of R.sub.5 and R.sub.6 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 --X.sub.1, --S--X.sub.2, --O--X.sub.2 or ##STR59## X.sub.1 is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, cyano, --S--X.sub.2 or --O--X.sub.2 ;
- X.sub.2 is alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, alkanoyl, substituted alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl or heteroarylcarbonyl;
- 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;
- X.sub.5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)carbonyl, or cyano;
- A is --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --(CH.sub.2).sub.n --, --(CH.sub.2).sub.n '--O--, --(CH.sub.2).sub.n '--NH--, --(CH.sub.2).sub.n '--S--CH.sub.2 --;
- n is 0, 1, 2 or 3;
- n' is 1 or 2; and
- X.sub.6 and X.sub.7 are the same or different and each is hydrogen or alkyl, or X.sub.6 is hydrogen and X.sub.7 is amino, substituted amino, acylamino or alkoxy;
- wherein the terms "alkyl" and "alkoxy" refer to groups having 1 to 10 carbon atoms;
- the term "cycloalkyl" refers to cycloalkyl 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 alkanoyl" refers to a group having the formula (substituted alkyl) ##STR60## or phenylalkanoyl; 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) or carboxyl groups;
- the term "substituted amino" refers to a group having the formula --NY.sub.1 Y.sub.2 wherein Y.sub.1 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, and Y.sub.2 is alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl, hydroxy, cyano, alkoxy, phenylalkoxy or amino;
- 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-furylmethyleneamino, phenylmethyleneamino substituted alkyl, wherein the alkyl group has 1 to 4 carbon atoms, groups;
- the terms "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, teterazolyl, azetinyl, 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-furylmethyleneamino, phenylmethyleneamino or substituted alkyl, wherein the alkyl group has 1 to 4 carbon atoms, groups.
- 15. A .beta.-lactam in accordance with claim 1, a salt of [3S-[3.alpha.(Z),4.beta.]]-2-[[[1-(2-amino-4-thiazolyl)-2-[[4-methyl-2-oxo-1-(sulfomethoxy)-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid.
- 16. A .beta.-lactam in accordance with claim 14, [3S-(3.alpha.,4.beta.)]-1-sulfomethoxy-3-amino-4-methyl-2-oxo-1-azetidine.
- 17. A .beta.-lactam in accordance with claim 1, a salt of [3S-[3.alpha.(R), 4.beta.]]-[[3-[[[[(4-ethyl-2,3-dioxo-1-peperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinyl]oxy]methanesulfonic acid.
- 18. A .beta.-lactam in accordance with claim 1, a salt of [3S-[3.alpha.(Z),4.beta.]]-[[3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinyl]oxy]methanesulfonic acid.
- 19. A .beta.-lactam in accordance with claim 14, [3S-(3.alpha.,4.alpha.)]-1-sulfomethoxy-3-amino-4-methyl-2-oxo-1-azetidine.
Parent Case Info
This application is a continuation-in-part application of co-pending U.S. patent application Ser. No. 433,175, filed Oct. 6, 1982, and now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4337197 |
Gordon et al. |
Jun 1982 |
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Foreign Referenced Citations (2)
Number |
Date |
Country |
0051381 |
May 1982 |
EPX |
2071650 |
Sep 1981 |
GBX |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
433175 |
Oct 1982 |
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