Claims for Patent: 5,164,402

Summary for Patent: 5,164,402

Title:	Azabicyclo quinolone and naphthyridinone carboxylic acids
Abstract:	Quinolone carboxylic acids 7-substituted by azabicyclo groups have antibacterial activity.
Inventor(s):	Katherine E. Brighty
Assignee:	Pfizer Inc
Application Number:	US07/650,835
Patent Claims:	1. A compound of the formula ##STR17## or a pharmaceutically acceptable acid addition salt thereof, wherein R1 is hydrogen, a pharmaceutically acceptable cation, or (C1 -C6) alkyl;Y is ethyl, vinyl, cyclopropyl, 2-fluoroethyl, p-fluorophenyl, or o,p-difluorophenyl; W is hydrogen, fluoro, chloro, bromo, C1 -C4 alkyl, C1 -C4 alkoxy, amino or aminomethyl; A is CH, CR, CCl, COCH3, C--CH3, C--CN or N; and R2 ##STR18## wherein R3, R6, R7, R9, R10, and R25 are each independently H, CH3, CH2 NH2, CH2 NHCH3 or CH2 NHC2 H5, and R6, R7, and R9 may also independently be NH2, NHCH3 or NHC2 H5, provided that not more than three of R3, R6, R7, R9, R10 and R25 are other than hydrogen and if three of these substituents are not hydrogen, at least one of them is methyl; and prodrugs of those compounds of formula I having free amino groups. 2. A compound according to claim 1 wherein R1 is hydrogen. 3. A compound according to claim 1 wherein Y is cyclopropyl or o,p-difluorophenyl. 4. A compound according to claim 1 wherein W is hydrogen, and A is CH or N. 5. A compound according to claim 1 wherein W is hydrogen and A is N. 6. A compound according to claim 1 wherein one or two of R3, R6, R7, R9, R10 and R25 are other than hydrogen. 7. A compound according to claim 6 wherein one of R3, R6, R7, R9, or R10 is CH2 NH2 or CH2 NHCH3, and another of R3, R6, R7, R9, R10 or R25 may be methyl. 8. A compound according to claim 6 wherein one of R6, R7, or R9 is NH2 or NHCH3 and another of R6, R7 or R9 or one of R3, R10 or R25 may be methyl. 9. A compound according to claim 8 wherein R6, R7 or R9 is amino and one of R3, R6, R7, R9, R10 or R25 may be methyl. 10. A compound according to claim 9 wherein R7 is amino and one of R3, R6, R9, R10 or R25 may be methyl. 11. A compound according to claim 6 wherein R7 is amino and R3, R6, R9, R10 or R25 are each hydrogen. 12. A compound according to claim 1, wherein said compound is7-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 7-([1α,2β,5α,6α]-6-amino-2-methyl-3-azabicyclo[3.1.0π-hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 7-([1α,6α,6α]-6-[(N-methyl)amino]-3-azabicyclo[3.1.0]hex-3-yl(-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, or 7-([1α,5α,6α]-6-aminomethyl-3-azabicyclo[3.1.0]-hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 13. A compound according to claim 1, wherein said compound is7-([1α,5α,6α]-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 7-([1α,5α,6α]-6-amino-3-azabicyclo[3.1.0]hex-3-yl(-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, p-toluenesulfonic acid salt, or 7-([1α,5α,6β]-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 14. A compound according to claim 1 wherein said compound is7-([1α,5α,6α]-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, or 7-([1α,5α,6α]-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, hydrate. 15. A compound according to claim 1 wherein said compound is7-([1α,5α,6α -6-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, hydrochloride salt, or 7-([1α,5α,6α]-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, methanesulfonic acid salt. 16. A compound according to claim 1 wherein R6, R7 or R9 contains an amino group which is covalently bonded through a peptide bond to one amino acid residue. 17. A compound according to claim 1 wherein R6, R7 or R9 contains an amino group which is covalently bonded through a peptide bond to a polypeptide of two or more amino acids. 18. A compound according to claim 1 wherein R6, R7 or R9 contains an amino group which is covalently bonded through a peptide bond to a polypeptide of two amino acids. 19. A compound according to claim 11 wherein the amino group of R7 is covalently bonded through a peptide bond to one amino acid residue. 20. A compound according to claim 11 wherein the amino group of R7 is covalently bonded rough a peptide bond to a polypeptide of two or more amino acids. 21. A compound according to claim 11 wherein the amino group of R7 is covalently bonded through a peptide bond to a polypeptide of two amino acids. 22. A compound according to claim 11 wherein said compound is7-([1α,5α,6α]-6-(L-Ala-amino)-3-azabicyclo[3.1.0]hex-3-yl-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid, hydrochloride salt. 23. A compound according to claim 21 wherein said compound is7-([1α,5α,6α]-6-(L-Ala-L-Leu-amino)-3-azabicyclo[3.1.0]-hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride salt. 24. A compound according to claim 21 wherein said compound is7-([1α,5α,6α]-6-(L-Ala-L-Ala-amino)-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, hydrochloride salt, or 7-([1α,5α,6α]-6-(L-Ala-L-Ala-amino)-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, methanesulfonic acid salt. 25. A compound according to claim 21 wherein said compound is7-([1α,5α,6α]-6(L-Ala-L-Ala-amino)-3-azabicyclo[3.1.0]hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. 26. An antibacterial composition comprising an antibacterially effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 27. A method for the treatment of a bacterial infection which comprises administering to a subject affected by a bacterial infection an antibacterially effective amount of a compound according to claim 1.