Zwitterionic forms of trovafloxacin

Details Zwitterionic forms of trovafloxacin Zwitterionic forms of trovafloxacin

1998-01-29

2000-05-23

Huang, Evelyn Mei

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546123, A61K 314375, C07D47104

Patent

active

060666471

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

This invention relates to the naphthyridone antibiotic trovafloxacin. More particularly, it relates to polymorphs and the pentahydrate of the zwitterionic form of thereof having the formula I, below, and methods for their preparation. The invention further relates to methods of using, and pharmaceutical compositions comprising, the compounds of the invention for treatment of bacterial infections in mammals. The antibacterial activity of the aforementioned naphthyridone antiliotic is described in U.S. Pat. Nos. 5,164,402 [the '402 patent] and 5,229,396 issued Nov. 17, 1992 and Jul. 20, 1993, respectively, the disclosures of which are hereby incorporated herein by reference in their entirety. The foregoing patents are assigned in common with the present application.
The zwitterionic forms of trovafloxacin are useful for the administration of the drug as a suspension.


SUMMARY OF THE INVENTION

According to a first embodiment of the invention there is provided a trovafloxacin zwitterionic crystal form having the formula ##STR2## which is selected from the group consisting of a) a non hygroscopic first polymorph PI exhibiting the following characteristic X-ray powder diffraction pattern


______________________________________ Peak no. 12 3 4 5 6 7 8 9 ______________________________________ 2.sub.-- .theta..sub.-- (.degree.) 6.9 9.8 11.3 12.0 13.9 16.1 16.6 17.1 17.4 Cu d space 12.7 9.0 7.9 7.4 6.4 5.5 5.4 5.2 5.1 ______________________________________ Peak no. 10 11 12 13 14 15 16 17 ______________________________________ 2.sub.-- .theta..sub.-- (.degree.) 19.7 22.9 23.6 24.9 25.4 25.9 27.7 29.5 Cu d space 4.5 3.9 3.8 3.6 3.5 3.4 3.2 3.0 ______________________________________ powder diffraction pattern


______________________________________ Peak no. 1 2 3 4 5 6 7 8 ______________________________________ 2.sub.-- .theta..sub.-- (.degree.) Cu 8.4 9.5 10.2 14.7 16.8 17.9 22.6 26.1 d space 10.6 9.3 8.7 6.0 5.3 5.0 3.9 3.4 ______________________________________ characteristic X-ray powder diffraction pattern


______________________________________ Peak no. 1 2 3 4 5 6 7 8 9 ______________________________________ 2.sub.-- .theta..sub.-- (.degree.) 6.6 8.6 12.7 13.3 15.9 18.6 19.2 20.1 21.0 Cu d space 13.3 10.3 7.0 6.6 5.5 4.8 4.6 4.4 ______________________________________ 4.2 Peak no. 10 11 12 13 14 15 16 17 ______________________________________ 2.sub.-- .theta..sub.-- (.degree.) 22.5 22.9 23.6 24.9 25.4 25.9 27.7 29.5 Cu d space 4.0 3.9 3.8 3.6 3.5 3.4 3.2 3.0 ______________________________________
A second embodiment of the invention relates to a process for preparing a zwitterion, of trovafloxacin, of the formula I which is selected from the group consisting of a non hygroscopic polymorph PI, a hygroscopic polymorph PII and a pentahydrate thereof, as described above, comprising compound of the formula I and vacuum drying to form said hygroscopic polymorph PII which exhibits the characteristic X-ray powder diffraction pattern described in claim 1; and vacuum drying; or removing the mother liquor and air drying the residue at room temperature to constant weight to form the pentahydrate; or solvent to form the non-hygroscopic first polymorph PI.
According to a third embodiment of the invention there is provided a process for preparing the metastable form of the zwitterion, of trovafloxacin, of the formula I, by the mixture to between 7.5 and 8.5 at an elevated temperature, removal of the mother liquor, washing the crystals with water and drying the crystals under vacuum at about 35 to about 40.degree. C.; or ##STR3## wherein A is hydrogen or an amine protecting group such as t-butyloxycarbonyl, benzyloxycarbonyl, (C.sub.1 -C.sub.6)alkylcarbonyl and benzyl; and t-butyl and (C.sub.1 -C.sub.6)alkyl; with an amine and/or carboxylic acid deprotecting agent, respectively.
A fourth embodiment of the invention provides a method of treating bacterial infections in a mammal which

REFERENCES:
patent: 4234578 (1980-11-01), Muller
patent: 4616002 (1986-10-01), Kamber
patent: 4965260 (1990-10-01), Lang
patent: 5164402 (1992-11-01), Brighty
patent: 5206256 (1993-04-01), Lang
patent: 5229396 (1993-07-01), Brighty

Affiliated with

Also associated with

Rating

Zwitterionic forms of trovafloxacin does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Zwitterionic forms of trovafloxacin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Zwitterionic forms of trovafloxacin will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1837309