Salt of naphthyridine carboxylic acid derivative

Abstract

7-(3-Aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof, processes for their preparation, pharmaceutical compositions comprising them, and their use in antibacterial therapy.

1 . 7-(3-Aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate. 
     
     
         2 . 7-(3-Aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate.nH 2 O, wherein n is in the range of from 1 to 4. 
     
     
         3 . A compound according to  claim 2  wherein n is 1.5. 
     
     
         4 . A compound according to  claim 2  having peaks at 2θ=8.0, 12.2 and 14.7° in its X-ray diffraction pattern. 
     
     
         5 . A compound according to  claim 2  having an X-ray diffraction pattern substantially as shown in  FIG. 7 . 
     
     
         6 . A compound according to  claim 2  where n is 3. 
     
     
         7 . A compound according to  claim 2  having peaks at 2θ=7.7, and 11.8° in its X-ray diffraction pattern. 
     
     
         8 . A compound according to  claim 2  having an X-ray diffraction pattern substantially as shown in  FIG. 6 . 
     
     
         9 . A compound according to  claim 2  which has a moisture content of from 4 to 6%. 
     
     
         10 . A compound according to  claim 2  which has a moisture content of from 9 to 11%. 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1 , together with a pharmaceutically acceptable carrier or excipient. 
     
     
         12 . A compound according to  claim 1 , for use as a pharmaceutical. 
     
     
         13 . A method of treating bacterial infections in humans and animals which comprises administering a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         14 . (canceled) 
     
     
         15 . A process for the preparation of a compound according to  claim 1 , which comprises reacting 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid with methanesulfonic acid and crystallizing the resulting compound from solution, and where desired or necessary, adjusting the hydration of the compound. 
     
     
         16 . A process for the preparation of a compound according to  claim 2 , comprising exposing 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate anhydrate or a solvate thereof to a relative humidity of at least 75%. 
     
     
         17 . A process according to  claim 16 , wherein the solvate is a solvate with one or more organic solvents selected from C 1 -C 4  haloalkanes and C 1 -C 8  alcohols. 
     
     
         18 . A solvate of 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate with one or more organic solvents.