Polymorph of zopolrestat monohydrate (3,4-dihydro-4-oxo-3-((5-trifluoromethyl)-2-benzothiazolyl)methyl)-1-phthalazineacetic acid monohydrate

• Main Authors: LAMBERT, JOHN FRANCIS, NORRIS, TIMOTHY
• Format: Patent
• Language: English
• Published: 26.01.2001
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The polymorph of the monohydrate form of zopolrestat (3,4-dihydro-4-oxo-3-((5-trifluoromethyl)-2-benzothiazolyl)methyl)-1-phthalazineacetic acid) has the characteristic x-ray powder diffraction pattern represented in the table above. The polymorph is prepared by reacting 3,4-dihydro-4-oxo-3-((5-trifluoromethyl)-2-benzothiazolyl)methyl)-1-phthalazineacetic ethyl ester with NaOH in an inert polar solvent, to form sodium 3,4-dihydro-4-oxo-3-((5-trifluoromethyl)-2-benzothiazolyl)methyl)-1-phthalazineacetate. This is adjusted to pH 7.5-8.5 to form a second solution comprising sodium 3,4-dihydro-4-oxo-3-((5-trifluoromethyl)-2-benzothiazolyl)methyl)-1-phthalazineacetate. A water soluble solvent is added to form a third solution, and the pH is adjusted to 1.5-2.5 with an inorganic acid to form the polymorph. Anhydrous zopolrestat may be prepared by heating the polymorph in water followed by drying. The polymorph may be used to treat, prevent or reverse complications arising from diabetes mellitus. In particular, the compound may be used to treat diabetic cardiomyopathy, reduce non-cardiac tissue damage, lower blood uric levels, inhibit aldose reductase activity, prevent anginal pain, prevent heart damage or treat diabetic nephropathy.