We report the structure-activity relationships of novel pyrimidine hydroxamate inhibitors of histone deacetylase 6 (HDAC6) that possess selectivity (20—300 fold) over Class I HDACs (1, 2, and 3). Of these, ACY-1083 was the most potent selective orally bioavailable compound and was chosen for investigation in animal models of disease. Compounds in this class were prepared using the scheme outlined below.

Identification of ACY-1083: A novel, potent, and highly selective HDAC6 inhibitor

251st National Meeting (2016)

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