Claims
- 1. A .beta.-lactam having a sulfonic acid salt substituent --SO.sub.3.sup..crclbar. M.sup..sym., wherein M.sup..sym. is hydrogen or a cation, in the 1-position and an amino substituent --NH.sub.2 in the 3-position.
- 2. A .beta.-lactam in accordance with claim 1 having a sulfonic acid salt substituent --SO.sub.3.sup..crclbar. M.sup..sym., wherein M.sup..sym. is hydrogen or a cation, in the 1-position, an amino substituent --NH.sub.2 in the 3-position and an alkoxy substituent having 1 to 4 carbon atoms in the 3-position.
- 3. A .beta.-lactam in accordance with claim 2 having a sulfonic acid salt substituent --SO.sub.3.sup..crclbar. M.sup..sym., wherein M.sup..sym. is hydrogen or a cation, in the 1-position, an amino substituent --NH.sub.2 in the 3-position and a methoxy substituent in the 3-position.
- 4. A .beta.-lactam in accordance with claim 1 having the formula ##STR82## wherein R.sub.2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl, or substituted phenyl, or one of R.sub.3 and R.sub.4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl, or 2-phenylethynyl; and M.sup..sym. is hydrogen or a cation.
- 5. A .beta.-lactam in accordance with claim 4 wherein R.sub.2 is hydrogen.
- 6. A .beta.-lactam in accordance with claim 4 wherein R.sub.2 is methoxy.
- 7. A .beta.-lactam in accordance with claim 5 wherein R.sub.3 and R.sub.4 are hydrogen.
- 8. A .beta.-lactam in accordance with claim 5 wherein R.sub.3 is hydrogen and R.sub.4 is methyl.
- 9. A .beta.-lactam in accordance with claim 5 wherein R.sub.3 is methyl and R.sub.4 is hydrogen.
- 10. A pharmaceutically acceptable salt, including inner salt, of a .beta.-lactam having a sulfonic acid substituent --SO.sub.3 H in the 1-position and an acylamino substituent other than N-(.gamma.-glutamylalanyl)amino in the 3-position, wherein the acyl portion of the group is derived from a carboxylic acid.
- 11. A pharmaceutically acceptable salt, including inner salt, or a .beta.-lactam in accordance with claim 10 having a sulfonic acid substituent --SO.sub.3 H in the 1-position, an acylamino substituent other than N-(.gamma.-glutamylalanyl)amino in the 3-position, wherein the acyl portion of the group is derived from a carboxylic acid, and an alkoxy substituent having 1 to 4 carbon atoms in the 3-position.
- 12. A pharmaceutically acceptable salt, including inner salt, or a .beta.-lactam in accordance with claim 10 having a sulfonic acid substituent --SO.sub.3 H in the 1-position, an acylamino substituent other than N-(.gamma.-glutamylalanyl)amino in the 3-position, wherein the acyl portion of the group is derived from a carboxylic acid, and a methoxy substituent in the 3-position.
- 13. A pharmaceutically acceptable salt, including inner salt of a .beta.-lactam in accordance with claim 10 having the formula ##STR83## wherein R.sub.1 --NH-- is acylamino, other than N-(.gamma.-glutamylalanyl)amino, wherein the acyl portion of the group is derived from a carboxylic acid; R.sub.2 is hydrogen or alkoxy of 1 to 4 carbon atoms; and R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl, or substituted phenyl or one of R.sub.3 and R.sub.4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl, or 2-phenylethynyl.
- 14. A .beta.-lactam in accordance with claim 13 wherein R.sub.2 is hydrogen.
- 15. A .beta.-lactam in accordance with claim 13 wherein R.sub.2 is methoxy.
- 16. A .beta.-lactam in accordance with claim 14 wherein R.sub.3 and R.sub.4 are hydrogen.
- 17. A .beta.-lactam in accordance with claim 14 wherein R.sub.3 is hydrogen and R.sub.4 is methyl.
- 18. A .beta.-lactam in accordance with claim 14 wherein R.sub.3 is methyl and R.sub.4 is hydrogen.
- 19. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is an aliphatic group having the formula ##STR84## wherein R.sub.5 is alkyl; cycloalkyl; alkoxy; alkenyl; cycloalkenyl; cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups.
- 20. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a carbocyclic aromatic group having the formula ##STR85## wherein n is 0, 1, 2 or 3; R.sub.6, R.sub.7, and R.sub.8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl; and R.sub.9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino, or [(alkylthio)thioxomethyl]thio.
- 21. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a heteroaromatic group having the formula ##STR86## wherein n is 0, 1, 2 or 3; R.sub.9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino or [(alkylthio)thioxomethyl]thio; and R.sub.10 is a substituted or unsubstituted 5-, 6-, or 7-membered heterocyclic aromatic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms.
- 22. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a group having the formula ##STR87## wherein R.sub.11 is (i) a group having the formula ##STR88## wherein R.sub.6, R.sub.7 and R.sub.8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6-, or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R.sub.12 is --N.dbd.CH--R.sub.11, ##STR89## alkylcarbonylamino, alkyl or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups.
- 23. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a group having the formula ##STR90## wherein R.sub.11 is (i) a group having the formula ##STR91## wherein R.sub.6, R.sub.7 and R.sub.8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy or 1 to 4 carbon atoms or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R.sub.13 is hydrogen, alkyl, cycloalkyl, alkylaminocarbonyl, ##STR92## or alkyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, R.sub.11, carboxyl, carboxyl salt, amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy(phenylmethoxy)phosphinyl, or dialkoxyphosphinyl substituents.
- 24. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a group having the formula ##STR93## wherein R.sub.11 is (i) a group having the formula ##STR94## wherein R.sub.6, R.sub.7 and R.sub.8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R.sub.14 is ##STR95## wherein n is 0, 1, 2, or 3, amino, alkylamino, (cyanoalkyl)amino, amido, alkylamido, (cyanoalkyl)amido, ##STR96##
- 25. A .beta.-lactam in accordance with claim 13 wherein R.sub.1 is a group having the formula ##STR97## wherein R.sub.11 is (i) a group having the formula ##STR98## wherein R.sub.6, R.sub.7 and R.sub.8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6-, or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R.sub.15 is hydrogen, alkylsulfonyl, --N.dbd.CH--R.sub.11, ##STR99## wherein R.sub.16 is hydrogen, alkyl, or halogen substituted alkyl, R.sub.11, alkyl, or alkyl substituted with one more more halogen, cyano, nitro, amino or mercapto groups.
- 26. A .beta.-lactam in accordance with claim 23 wherein R.sub.11 is 2-amino-4-thiazolyl.
- 27. A .beta.-lactam in accordance with claim 26: a salt of [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-2-oxo-1-azetidinesulfonic acid.
- 28. A .beta.-lactam in accordance with claim 26: a salt of [3S(Z)]-3-[[(2-amino-4-thiazolyl)[(carboxymethoxy)imino]acetyl]amino]-2-oxo-1-azetidinesulfonic acid.
- 29. A .beta.-lactam in accordance with claim 26: a salt of [3S(Z)]-3-[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-oxo-1-azetidinesulfonic acid.
- 30. A .beta.-lactam in accordance with claim 26: a salt of [3S-[3.alpha.(Z),4.beta.]]-3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 31. A .beta.-lactam in accordance with claim 26: a salt of [3S-[3.alpha.(Z),4.beta.]]-3-[[[(carboxymethoxy)imino](2-amino-4-thiazolyl)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 32. A .beta.-lactam in accordance with claim 26: a salt of [3S-[3.alpha.(Z),4.beta.]]-3-[[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 33. A .beta.-lactam in accordance with claim 32: [3S-[3.alpha.(Z),4.beta.]]-3-[[(2-amino-4-thiazolyl[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, dipotassium salt.
- 34. A .beta.-lactam in accordance with claim 26: a salt of [3S-[3.alpha.(Z),4.alpha.]]-3-[[2-amino-4-thiazolyl)methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 35. A .beta.-lactam in accordance with claim 26: a salt of [3S-[3.alpha.(Z),4.alpha.]]-3-[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 36. A .beta.-lactam in accordance with claim 25 wherein R.sub.1 is a group having the formula ##STR100##
- 37. A .beta.-lactam in accordance with claim 36 wherein R.sub.1 is a group having the formula ##STR101##
- 38. A .beta.-lactam in accordance with claim 37: a salt of [3S(R*)]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]amino]phenylacetyl]amino]-2-oxo-1-azetidinesulfonic acid.
- 39. A .beta.-lactam in accordance with claim 37: a salt of [3S-[3.alpha.(R*),4.beta.]]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 40. A .beta.-lactam in accordance with claim 37: a salt of [3S-[3.alpha.(R*),4.alpha.]]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 41. A .beta.-lactam in accordance with claim 22 wherein R.sub.1 is a group having the formula ##STR102##
- 42. A .beta.-lactam in accordance with claim 41: a salt of [3S(R*)]-3-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-2-oxo-1-azetidinesulfonic acid.
- 43. A .beta.-lactam in accordance with claim 41: a salt of [3S-[3.alpha.(R*),4.beta.]]-3-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 44. A .beta.-lactam in accordance with claim 41: a salt of [3S-[3.alpha.(R*),4.alpha.]]-3-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
- 45. A method of treating bacterial infections in mammals which comprises administering to a mammal in need thereof an effective amount of a pharmaceutically acceptable salt, including inner salt, of a .beta.-lactam having the formula ##STR103## wherein R.sub.1 is acyl, other than N-(.gamma.-glutamylalanyl), derived from a carboxylic acid; R.sub.2 is hydrogen or alkoxy of 1 to 4 carbon atoms; and R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R.sub.3 and R.sub.4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl.
- 46. An antibacterial composition comprising an effective amount of a pharmaceutically acceptable salt, including inner salt, of a .beta.-lactam having the formula ##STR104## wherein R.sub.1 is acyl, other than N-(.gamma.-glutamylalanyl), derived from a carboxylic acid; R.sub.2 is hydrogen or alkoxy of 1 to 4 carbon atoms; and R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R.sub.3 and R.sub.4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl, and a pharmaceutically acceptable carrier therefor.
- 47. A .beta.-lactam having the formula ##STR105## wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R.sub.3 and R.sub.4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M.sup..sym. is a cation.
- 48. A .beta.-lactam in accordance with claim 13: [3S-[3.alpha.(Z),4.beta.]]-3-[[(2-amino-4-thiazolyl)-[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.
Parent Case Info
This application is a continuation-in-part of copending U.S. patent application Ser. No. 188,893, filed Sept. 29, 1980, and now abandoned, which is a continuation-in-part of copending U.S. patent application Ser. No. 119,276, filed Feb. 7, 1980, and now abandoned.
US Referenced Citations (13)
Foreign Referenced Citations (2)
Number |
Date |
Country |
21678 |
Jan 1981 |
EPX |
7972813 |
Dec 1980 |
JPX |
Non-Patent Literature Citations (1)
Entry |
Imada, III et al. Nature 289, 590-1. |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
188893 |
Sep 1980 |
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Parent |
119276 |
Feb 1980 |
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