CA2884481C — Method of synthesizing thyroid hormone analogs and polymorphs thereof

USPTO Abstract

Abstract The disclosure describes methods of synthesis of pyridazinone compounds such as 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 ("Compound A"), 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 such as Form I, processes for preparing same, and pharmaceutical compositions comprising same. Further disclosed is a method for treating resistance to thyroid hormone in a subject having at least one TRr3 mutation, nonalcoholic steatohepatitis, fatty liver disease, or hypercholesterolemia. Date Recue/Date Received 2020-08-10