Claims
- 1. A compound of the formula ##STR306## wherein n is zero, 1 or 2; X.sub.3 is H or Br, 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 H or the residue of an ester group readily hydrolyzable in vivo selected from 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, ##STR307## 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, R.sup.14 is ##STR308## 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; and R.sup.18 is H, (C.sub.2 -C.sub.5)alkanoyl, (C.sub.2 -C.sub.5)alkoxycarbonyl, pyrazinecarbonyl, benzoyl, CF.sub.3 CO or CONR.sup.8 R.sup.9 ; one of R.sup.12 and R.sup.13 is hydrogen and the other is vinyl, (C.sub.1 -C.sub.4)alkylsulfonyl, furyl, thienyl, N-methylpyrrolyl, N-acetylpyrrolyl, ##STR309## 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, hydroxy, carboxyl, (C.sub.2 -C.sub.5)alkoxycarbonyl, (C.sub.1 -C.sub.5)alkylcarbonyl, phenyl, benzyl, napthyl, 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.8 and R.sup.9 are each H, (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 H, (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.12 or R.sup.13 contains a basic nitrogen atom or a pharmaceutically acceptable cationic salt of said compound wherein R.sup.1 is H or R.sup.12 or R.sup.13 contains a carboxyl group.
- 2. A compound according to claim 1 wherein n is zero or 2, one of R.sup.12 and R.sup.13 is H and the other is vinyl, 2-furyl, 2-thienyl, N-methylpyrrol-2-yl, N-acetylpyrrol-2-yl, 4-pyrimidinyl, 2-pyrimidinyl, 2-pyrazinyl, ##STR310## and R.sup.18 is H or CH.sub.3 CO.
- 3. A compound according to claim 2 wherein one of R.sup.12 and R.sup.13 is H and the other is 2-thiazolyl, 3-isothiazolyl, 2-pyrimidinyl, 4-pyrimidinyl, 2-pyrazinyl or ##STR311## where X.sub.1 is S or NR.sup.11 and R.sup.11 is H, CH.sub.3, C.sub.2 H.sub.5 or C.sub.6 H.sub.5 CH.sub.2.
- 4. A compound according to claim 3 wherein X.sub.3 is H.
- 5. A compound according to claim 4 wherein one of R.sup.12 and R.sup.13 is H and the other is 2-thiazolyl.
- 6. A compound according to claim 5 wherein n is 2, R.sup.18 is CH.sub.3 CO and the 6-position substituent has (6 alpha, 8R) or (6 beta, 8R) stereochemistry.
- 7. A compound according to claim 4 wherein n is zero, one of R.sup.12 and R.sup.13 is H and the other is 2-benzothiazolyl or ##STR312## where R.sup.11 is H, CH.sub.3, C.sub.2 H.sub.5 or C.sub.6 H.sub.5 CH.sub.2 ; and R.sup.18 is H.
- 8. A compound according to claim 1 wherein R.sup.1 is R.sup.a.
- 9. A compound according to claim 8 wherein R.sup.a is allyl.
- 10. A compound according to claim 1 wherein R.sup.1 is R.sup.b.
- 11. A compound according to claim 10 wherein R.sup.b is H, a pharmaceutically acceptable cationic salt thereof, ##STR313##
- 12. A compound according to claim 11 wherein R.sup.b is H, a pharmaceutically acceptable cationic salt thereof, ##STR314##
- 13. A compound according to claim 11 wherein R.sup.b is H, a sodium or potassium salt thereof, pivaloyloxymethyl, 1-(ethoxycarbonyloxy)ethyl or CH.sub.2 OCOR.sup.14 where R.sup.14 is ##STR315## and R.sup.15 is D-2-amino-2-phenylacetamido or D-2-amino-2-(4-hydroxyphenyl)acetamido.
- 14. A compound according to claim 13 of the formula ##STR316## or a sodium or potassium salt thereof.
- 15. A compound according to claim 13 wherein n is zero.
- 16. A compound according to claim 15 wherein X.sub.3 and R.sup.18 are each H.
- 17. A compound according to claim 16 wherein one of R.sup.12 and R.sup.13 is H and the other is 2-thiazolyl, 2-benzothiazolyl, 1-methyl-2-benzimidazolyl or 1-ethyl-2-benzimidazolyl.
- 18. A compound according to claim 17 wherein one of R.sup.12 and R.sup.13 is H and the other is benzothiazol-2-yl.
- 19. The compound according to claim 18: (6 beta, 8S)-6-[2-benzothiazolyl) (hydroxy)]methylpenicillanic acid or a sodium or potassium salt thereof.
- 20. A compound according to claim 17 wherein one of R.sup.12 and R.sup.13 is H and the other is 1-methyl-2-benzimidazolyl or 1-ethyl-2-benzimidazolyl.
- 21. The compound according to claim 20: (6 beta, 8S)-6-[(1-methyl-2-benzimidazolyl) (hydroxy)]methylpenicillanic acid or a sodium or potassium salt thereof.
- 22. A pharmaceutical composition for treating bacterial infections which comprises in a weight ratio of 1:3 to 3:1 a compound of claim 12 and a beta-lactam antibiotic.
- 23. A pharmaceutical composition for treating bacterial infections which comprises a pharmaceutically acceptable carrier and a compound according to claim 11 wherein R.sup.b is --CH.sub.2 OCOR.sup.14.
- 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 22.
- 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 continuation-in-part of copending application Ser. No. 679,192 filed Dec. 11, 1984, which is a continuation-in-part of the abandoned parent application Ser. No. 575,354 filed Jan. 30, 19874, both now abandoned.
US Referenced Citations (5)
Foreign Referenced Citations (4)
Number |
Date |
Country |
0005889 |
Dec 1979 |
EPX |
0018305 |
Oct 1980 |
EPX |
0050805 |
May 1982 |
EPX |
2053220 |
Feb 1981 |
GBX |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
679192 |
Dec 1984 |
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Parent |
575354 |
Jan 1984 |
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