Hoffmann-la Roche Inc.

Madrigal Pharmaceuticals, Inc.

Edward Hung Yang Chiang

Martha Jean Kelly

Rebecca Taub

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.

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Yardley, PA, United States of America

Edward Hung Yang Chiang