METHODS OF SYNTHESIZING THYROID HORMONE ANALOGS AND POLYMORPHS THEREOF
The disclosure describes methods of synthesis of pyridazinone compounds as thyroid hormone analogs and their prodrugs. Preferred methods according to the disclosure allow for large-scale preparation of pyridazinone compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of pyridazinone compounds in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of a pyridazinone compound. Further disclosed is a method for treating resistance to thyroid hormone in a subject having at least one TRβ mutation.
1 . A method for treating nonalcoholic steatohepatitis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a morphic form of 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile (Form I) characterized by an X-ray powder diffraction pattern including peaks at about 10.5, 18.7, 22.9, 23.6, and 24.7 degrees 2θ.
2 . The method of claim 1 , wherein the X-ray powder diffraction pattern further includes peaks at about 8.2, 11.2, 15.7, 16.4, 17.7, 30.0, and 32.2 degrees 2θ.
3 . The method of claim 1 , wherein the morphic form is characterized by an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 1 .
4 . The method of claim 1 , wherein the morphic form has a purity of Compound A of 95% or greater.