Claims
- 1. A compound of the formula ##STR61## and pharmaceutically acceptable salts thereof; wherein R is ##STR62## or R.sub.1 -[R.sub.5 N-acyl].sub.n ; x is an integer of from one to five; x' is zero, one or two, R.sub.1 is hydrogen, lower alkyl, benzyl or ##STR63## wherein R.sub.2 is hydrogen, amino, or lower alkyl group of from one to four carbon atoms, optionally substituted by from one to three chlorine or fluorine atoms, R.sub.5 is hydrogen or lower alkyl and N-acyl is an aminoacyl moiety derived from a carboxylic acid of from two to ten carbon atoms, optionally substituted by from one to three of the following groups, hydroxyl, carboxyl, ##STR64## amino, lower alkylamido, carbamido, carbonyl oxygen, lower alkoxy, lower alkylthio, or sulfonic acid, n is an integer of from one to four; R.sub.3 is phenyl, 4-hydroxyphenyl, 2-thienyl or cyclohexa-1,4-dien-1-yl and R.sub.4 is acetoxy, carbamoyloxy, or a heterocyclicthio group where the heterocyclic moiety is unsubstituted or substituted by a methyl group and the heterocycle is a thiadiazolyl, triazolyl or tetrazolyl group or the heterocyclicthio group has the formula ##STR65## wherein Z is ##STR66## or CH.sub.2 -OH and n' is an integer of from one to four.
- 2. The compounds of claim 1 wherein R-NH is in the para position.
- 3. The compounds of claim 2 wherein the optically active R.sub.1 aminoacyl fragment is in the D form.
- 4. The compounds of claim 2 wherein NH-acyl if D-alanyl, L-glutaminyl, D-glutaminyl, L-pyroglutamyl or L-lysyl.
- 5. The compounds of claim 4 wherein R.sub.2 is a carbon fragment of from one to two carbon atoms.
- 6. The compounds of claim 5 wherein R.sub.3 is phenyl or p-hydroxyphenyl.
- 7. The compounds of claim 6 wherein R.sub.4 is acetoxy.
- 8. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 9. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 10. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-DL-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 11. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 12. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-6-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 13. The compounds of claim 1 having the name N-[6-[4-(L-pyroglutamylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 14. The compounds of claim 1 having the name N-[6-[4-(L-pyroglutamylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 15. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 16. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1-H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 17. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-Dl-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino2-phenylacetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 18. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-alpha-aminoisobutyrylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 19. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-propylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 20. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-asparaginylamino)phenyl-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically-acceptable salts thereof.
- 21. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 22. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-phenylacetamido]-3-[([5-methyl-1,3,4-thiadiazoyl-2-yl]thio)methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 23. The compounds of claim 1 having the name N-[6-[4-(L-pyroglutamylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 24. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-DL-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 25. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-DL-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 26. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 27. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 28. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-L-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 29. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-DL-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[([4-methyl-1,3,4-thiadiazoyl-2-yl]thio)methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 30. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-asparaginylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 31. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 32. The compounds of claim 1 having the name N-[6-[4-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 33. The compounds of claim 1 having the name N-[6-[4-(N,N'-diacetyl-DL-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 34. The compounds of claim 1 having the name N-[6-[4-(N,N'-diacetyl-DL-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-(D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 35. The compounds of claim 1 having the name N-[6-[3-(N-acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamio]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 36. The compounds of claim 1 having the name N-[6-[4-(D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 37. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-4-hydroxy-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 38. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-4-hydroxy-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 39. A compound of claim 1 having the name N-[6-[4-[N-Acetyl-4-(acetyloxy)-L-prolylamino]phenyl]-1,2-dihydro-2-oxoniotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 40. A compound of claim 1 having the name N-[6-[4-[N-Acetyl-4-(formyloxy)-L-prolylamino]phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 41. A compound of claim 1 having the name N-[6-[4-[N-Methyl-5-oxo-L-prolylamino]phenyl]-1,2-dihydro-2-oxo-nicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 42. A compound of claim 1 having the name N-[6-[4-(N,N'-Diacetyl-L-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 43. A compound of claim 1 having the name N-[6-[4-[N-Acetyl-4-(1-oxopropoxy)-L-prolylamino]-phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1-H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 44. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-D-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxymethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 45. A compound of claim 1 having the name N-[6-[4-(L-Glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-carboxylmethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 46. A compound of claim 1 having the name N-[6-[4-[N-Acetyl-4-(1-oxopropoxy)-L-prolylamino]-phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 47. A compound of claim 1 having the name N-[6-[4-[N-Acetyl-4-(1-oxopropoxy)-L-prolylamino]phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 48. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-D-alanylamino)phenyl]-1,2-dihydro-2-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[[1-(2-carboxyethyl)-1H-tetrazol-5-yl]thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 49. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-L-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-[[(1-sulfomethyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 50. A compound of claim 1 having the name N-[6-[4-(N-Acetyl-L-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid and pharmaceutically acceptable salts thereof.
- 51. A pharmaceutical composition comprising from 30 mg to 1000 mg of a compound of claim 1 and a pharmaceutical carrier.
- 52. A method for treating infections which comprises administering the pharmaceutical composition of claim 51.
Parent Case Info
This is a continuation-in-part of copending U.S. application, Ser. No. 19,983, filed Mar. 12, 1979, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
3954734 |
Doub et al. |
May 1976 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
19983 |
Mar 1979 |
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