Claims
- 1. A compound of the formula ##STR303## wherein n is zero, 1 or 2; R.sup.1 is R.sup.a or R.sup.b where R.sup.a is the residue of a carboxy protecting group selected from tetrahydropyranyl, allyl, benzyl, 4-nitrobenzyl, benzhydryl, 2,2,2-trichloroethyl, t-butyl and phenacyl; and R.sup.b is hydrogen or the residue of an ester group readily hydrolyzable in vivo selected from 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, ##STR304## where R.sup.4 and R.sup.5 are each hydrogen or CH.sub.3, R.sup.6 is (C.sub.1 -C.sub.5)-alkyl, and R.sup.14 is ##STR305## where R.sup.15 is 2-phenylacetamido, 2-phenoxyacetamido, D-2-amino-2-phenylacetamido, D-2-amino-2-(4-hydroxyphenyl)acetamido, 2-carboxy-2-phenylacetamido, 2-carboxy-2-(2-thienyl)acetamido, 2-carboxy-2-(3-thienyl)-acetamido, D-2-(4-ethyl-2,3-dioxopiperazinocarbonylamino)-2-phenylacetamido or 2,2-dimethyl-4-phenyl-5-imidazolidinone-1-yl;
- one of R.sup.2 and R.sup.3 is hydrogen and the other is Cl, CH.sub.2 OH, vinyl, (C.sub.1 -C.sub.4)alkylthio, (C.sub.1 -C.sub.4)alkylsulfonyl, furyl, thienyl, N-methylpyrrolyl, N-acetylpyrrolyl, ##STR306## and m is 2 or 3, p is zero or 1, t is zero, 1 or 2, X.sub.1 is S, O or NR.sup.11, R.sup.7 is hydrogen, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, allyloxy, hydroxyl, carboxyl, (C.sub.2 -C.sub.5)-alkoxycarbonyl, (C.sub.1 -C.sub.5)alkylcarbonyl, phenyl, benzyl, naphthyl, pyridyl NR.sup.8 R.sup.9, CONR.sup.8 R.sup.9, NHCOR.sup.10, NO.sub.2, Cl, Br, CF.sub.3 or SR.sup.8 ; and R.sup.9 are each hydrogen, (C.sub.1 -C.sub.4)-alkyl, phenyl or benzyl; R.sup.10 is (C.sub.1 -C.sub.4)alkyl, CF.sub.3 or phenyl; and R.sup.11 is hydrogen, (C.sub.1 -C.sub.3) alkyl, C.sub.6 H.sub.5 CH.sub.2 or CH.sub.3 CO; R.sup.16 and R.sup.17 are each H, (C.sub.1 -C.sub.4)alkyl, (C.sub.2 -C.sub.4)-hydroxyalkyl, or taken together with the nitrogen atom to which they are attached R.sup.16 and R.sup.17 form a pyrrolidino, piperidino, morpholino, thiomorpholino or 4-methylpiperazino group; or a pharmaceutically acceptable acid addition salt of said compound where R.sup.2 or R.sup.3 contains a basic nitrogen atom, or a pharmaceutically acceptable cationic salt of said compound wherein R.sup.1 is hydrogen or R.sup.2 or R.sup.3 contains a carboxyl group.
- 2. A compound according to claim 1 wherein R.sup.1 is R.sup.a.
- 3. A compound according claim 1 wherein R.sup.1 is R.sup.b.
- 4. A compound according to claim 3 wherein R.sup.b is H, a pharmaceutically acceptable cationic salt thereof, ##STR307##
- 5. A compound according to claim 4 wherein R.sup.b is H, a pharmaceutically acceptable cationic salt thereof, ##STR308##
- 6. A compound according to claim 4 wherein R.sup.b is H, a sodium or potassium salt thereof, pivaloyloxymethyl or CH.sub.2 OCOR.sup.14 where R.sup.14 is ##STR309## and R.sup.15 is D-2-amino-2-phenylacetamido or D-2-amino-2-(4-hydroxyphenyl)acetamido.
- 7. A compound according to claim 6 wherein n is zero or 2, one of R.sup.2 and R.sup.3 is H and the other is CH.sub.2 OH, methylsulfonyl, 2-furyl, 2-thienyl, N-methylpyrrolyl, ##STR310##
- 8. A compound according to claim 7 wherein n is 2.
- 9. A compound according to claim 8 wherein one of R.sup.2 and R.sup.3 is H and the other is 2-pyridyl, N-oxo-2-pyridyl, 2-quinolyl, 3-allyloxy-2-pyridyl, 3-methoxy-2-pyridyl, 4-methoxy-2-pyridyl, 3-hydroxy-2-pyridyl, 6-methyl-2-pyridyl, 1-methyl-2-imidazolyl, 2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 4-methyl-2-thiazolyl, 3-isothiazolyl, 4-pyrimidinyl, 2-pyrimidinyl, 4,6-dimethyl-2-pyrimidinyl, 2-pyrazinyl, 2-methyl-1,2,4-triazol-3-yl or benzothiazol-2-yl.
- 10. A compound according to claim 9 wherein one of R.sup.2 and R.sup.3 is H and the other is 2-pyridyl, 3-allyl-oxy-2-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 3-hydroxy-2-pyridyl, 4-methoxy-2-pyridyl, 2-thiazolyl or 3-isothiazolyl.
- 11. A compound according to claim 10 wherein one of R.sup.2 and R.sup.3 is H and the other is 2-pyridyl or a sodium or potassium salt thereof.
- 12. A compound according to claim 10 wherein one of R.sup.2 and R.sup.3 is H and the other is 3-hydroxy-2-pyridyl or a sodium or potassium salt thereof.
- 13. A compound according to claim 10 wherein one of R.sup.2 and R.sup.3 is H and the other is 2-pyrazinyl or a sodium or potassium salt thereof.
- 14. A compound according to claim 10 wherein one of R.sup.2 and R.sup.3 is H and the other is 2-thiazolyl or a sodium or potassium salt thereof.
- 15. A compound according to claim 10 wherein one of R.sup.2 and R.sup.3 is H and the other is 3-isothiazolyl or a sodium or potassium salt thereof.
- 16. The compound according to claim 11:
- 1,1-dioxo-6(E)-(2-pyridyl)methylenepenicillanic acid.
- 17. The compound according to claim 14:
- 1,1-dioxo-6(E)-(2-thiazolyl)methylenepenicillanic acid.
- 18. The compound according to claim 15:
- 1,1-dioxo-6(E)-(3-isothiazolyl)methylenepenicillanic acid.
- 19. A compound according to claim 2 wherein R.sup.a is allyl.
- 20. A pharmaceutical composition for treating bacterial infections which comprises in a weight ratio of 1:3 to 3:1 a compound of claim 5 and a beta-lactam antibiotic.
- 21. A pharmaceutical composition of claim 20 wherein the beta-lactam antibiotic is
- amoxicillin,
- ampicillin,
- apalcillin,
- azlocillin,
- azthreonam,
- bacampicillin,
- carbenicillin,
- carbenicillin indanyl,
- carbenicillin phenyl,
- cefaclor,
- cefadroxil,
- cefaloram,
- cefamandole,
- cefamandole nafate,
- cefaparole,
- cefatrizine,
- cefazolin,
- cefbuperazone
- cefmenoxime,
- cefonicid,
- cefodizime,
- cefoperazone,
- ceforanide,
- cefotaxime,
- cefoxitin,
- cefotiam,
- cefpiramide,
- cefpirome,
- cefsulodin,
- ceftazidime
- ceftizoxime,
- ceftriaxone,
- cefuroxime,
- cephacetrile,
- cephalexin,
- cephaloglycin,
- cephaloridine,
- cephalothin,
- cephapirin,
- cephradine,
- cyclacillin,
- epicillin
- furazlocillin,
- hetacillin,
- lenampicillin
- levopropylcillin,
- mecillinam,
- mezlocillin,
- penicillin G,
- penicillin V,
- phenethicillin,
- piperacillin,
- pirbenicillin,
- pivampicillin,
- sarmoxicillin,
- sarpicillin,
- suncillin,
- talampicillin,
- ticarcillin, 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(N-methylpyrrolidinium)methyl-3-cephem-4-carboxylate, or 7-[D-(2-[4-carboxy-5-imidazolcarboxamido])-2-phenylacetamido]-3-[4-(2-sulfonatoethyl)pyridinium]-3-cephem-4-carboxylic acid; or a pharmaceutically acceptable salt thereof.
- 22. A pharmaceutical composition according to claim 21 wherein the beta-lactam antibiotic is ampicillin, hetacillin, pivampicillin, bacampicillin, talampicillin, amoxicillin or lenampicillin.
- 23. A pharmaceutical composition for treating bacterial infections which comprises a pharmaceutically acceptable carrier and a compound according to claim 4 wherein R.sup.b is ##STR311##
- 24. A method of treating a bacterial infection in a mammalian subject, which comprises administering to a mammal in need of such treatment an antibacterially effective amount of a pharmaceutical composition according to claim 20.
- 25. A method of treating a bacterial infection in a mammalian subject, which comprises administering to a mammal in need of such treatment an antibacterially effective amount of a pharmaceutical composition according to claim 23.
CROSS REFERENCE TO RELATED APPLICATION
This application is a division of copending application Ser. No. 892,001, filed July 30, 1986, now U.S. Pat. No. 4,826,833 which is a continuation-in-part of application Ser. No. 679,192 filed Dec. 11, 1984, now abandoned which is a continuation-in-part of the abandoned parent application Ser. No. 575,354 filed Jan. 30, 1984.
US Referenced Citations (5)
Foreign Referenced Citations (5)
Number |
Date |
Country |
5889 |
Dec 1979 |
EPX |
18305 |
Oct 1980 |
EPX |
50805 |
May 1982 |
EPX |
0069373 |
Jan 1983 |
EPX |
2053220 |
Feb 1981 |
GBX |
Divisions (1)
|
Number |
Date |
Country |
Parent |
892001 |
Jul 1986 |
|
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
679192 |
Dec 1984 |
|
Parent |
575354 |
Jan 1984 |
|