Abstract: Formula-I where HX is succinic acid, l-hydroxy-2-naphthoic acid, L- (+)-tartaric acid, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, d, 1-lactic acid benzoic aicd, fumaric acid, and p-toluenesulphonic aicd.
INTRODCTION
The present invention relates to novel salts of Voriconazole, an anti-fungal drug. The present invention further relates to preparation of novel salts of Voriconazole with succinate, xinafoate, L- (+)-tartrate, 3-hydroxy-3-methylglutarate (meglutate), formate, acetate, propionate, d, 1-lactate, benzoate, fumarate, p-toluenesulphonate etc., useful in the preparation of the Voriconazole formulations. The structure of Voriconazole salt, shown in Formula-I is,
where HX is succinic acid, l-hydroxy-2-naphthoic acid, L- (+)-tartaric acid, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, (d, l)-lactic acid benzoic aicd, fumaric acid, p-toluenesulphonic aicd.
BACKGROUND OF THE INVENTION
Voriconazole is a triazole antifungal agent structurally related to fluconazole. Its antifungal activity and synthesis is reported in Bioorganic & Medicinal Chemistry Letters Vol.6. No. 16, 2011-2036,1996. Voriconazole acts principally by inhitibiting cytochrome P450 14a-demethylase (P45014DM). Thus the conversion of lanosterol to ergosterol is
1. Novel salts of Voriconazole, shown in Formula-I,
Formula-I where HX is succinic acid, 1-hydroxy-2-naphthoic acid, L- (+)-tartaric acid,, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, d,l-lactic acid, benzoic acid, fumaric acid, p-toluenesulphonic aicd.
2. Crystalline solid Voriconazole succinate of claim 1 further having peaks in the powder X-ray diffraction pattern at 12.697, 13.883, 16.000, 16.583, 17.470, 19.903, 21.270, 26.166, and 28.313.
3. Crystalline solid Voriconazole xinafoate of claim 1 further having peaks in the powder X-ray diffraction pattern at 10.347, 12.162, 12.640, 13.806, 14.788, 15.931, 16.525, 17.403, 19.765, 21.220, 26.150, 26.535, and 28.231
4. Crystalline solid Voriconazole L-(+)-tartrate of claim 1 further having peaks in the powder X-ray diffraction pattern at 5.078, 10.176, and 20.439.
5. Crystalline solid Voriconazole meglutate of claim 1 further having peaks in the powder X-ray diffraction pattern at 6.825, 13.759, 16.480,17.350, and 19.715.
6. A Process for the prearation of the salts of Voriconazole of claim 1 comprising:
a) dissolving the Voriconazole in a warm organic solvent such as methanol, ethanol, isopropyl alcohol, t-butanol, n-butanol, toluene, xylene, acetone, methyl ethyl
ketone, methyl isobutyl ketone, ethyl acetate, cyclohexane, methylene chloride, chloroform, etc.
b) then adding molar equivalent quantity of the respective organic acid
c) isolating the acid addition salt either by crystallization from the solvent used or by distilling of solvent used in the process
d) drying the wet salt to get the pharmaceutically useful salts of Voriconazole.
7. A pharmaceutical formulation using the Voriconazole salts according to claim 1. Dated this 14th day of July, 2006
| # | Name | Date |
|---|---|---|
| 1 | 1027-CHE-2005 CORRESPONDENCE OTHERS 31-03-2010.pdf | 2010-03-31 |
| 1 | 1027-CHE-2005_EXAMREPORT.pdf | 2016-07-02 |
| 2 | 1027-che-2005-abstract.pdf | 2011-09-03 |
| 2 | 1027-CHE-2005 AMANDED PAGES OF SPECIFICATION 31-03-2010.pdf | 2010-03-31 |
| 3 | 1027-che-2005-claims.pdf | 2011-09-03 |
| 3 | 1027-CHE-2005 AMANDED CLAIMS 31-03-2010.pdf | 2010-03-31 |
| 4 | 1027-CHE-2005 CORRESPONDENCE OTHERS 12-11-2010.pdf | 2010-11-12 |
| 4 | 1027-che-2005-correspondence others.pdf | 2011-09-03 |
| 5 | abs-1027.jpg | 2011-09-03 |
| 5 | 1027-che-2005-discription complete.pdf | 2011-09-03 |
| 6 | abs-1027-che-2005.jpg | 2011-09-03 |
| 6 | 1027-che-2005-form1.pdf | 2011-09-03 |
| 7 | 1027-che-2005-form5.pdf | 2011-09-03 |
| 8 | abs-1027-che-2005.jpg | 2011-09-03 |
| 8 | 1027-che-2005-form1.pdf | 2011-09-03 |
| 9 | abs-1027.jpg | 2011-09-03 |
| 9 | 1027-che-2005-discription complete.pdf | 2011-09-03 |
| 10 | 1027-CHE-2005 CORRESPONDENCE OTHERS 12-11-2010.pdf | 2010-11-12 |
| 10 | 1027-che-2005-correspondence others.pdf | 2011-09-03 |
| 11 | 1027-CHE-2005 AMANDED CLAIMS 31-03-2010.pdf | 2010-03-31 |
| 11 | 1027-che-2005-claims.pdf | 2011-09-03 |
| 12 | 1027-che-2005-abstract.pdf | 2011-09-03 |
| 12 | 1027-CHE-2005 AMANDED PAGES OF SPECIFICATION 31-03-2010.pdf | 2010-03-31 |
| 13 | 1027-CHE-2005_EXAMREPORT.pdf | 2016-07-02 |
| 13 | 1027-CHE-2005 CORRESPONDENCE OTHERS 31-03-2010.pdf | 2010-03-31 |