Discovery of 2-[3, 5-dichloro-4-(5-isopropyl-6-oxo-1, 6-dihydropyridazin-3-yloxy) phenyl]-3, 5-dioxo-2, 3, 4, 5-tetrahydro [1, 2, 4] triazine-6-carbonitrile (MGL-3196), a …

MJ Kelly, S Pietranico-Cole, JD Larigan…

Index: Kelly, Martha J.; Pietranico-Cole, Sherrie; Larigan, J. Douglas; Haynes, Nancy-Ellen; Reynolds, Charles H.; Scott, Nathan; Vermeulen, John; Dvorozniak, Mark; Conde-Knape, Karin; Huang, Kuo-Sen; So, Sung-Sau; Thakkar, Kshitij; Qian, Yimin; Banner, Bruce; Mennona, Frank; Danzi, Sara; Klein, Irwin; Taub, Rebecca; Tilley, Jefferson Journal of Medicinal Chemistry, 2014 , vol. 57, # 10 p. 3912 - 3923

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Citation Number: 5

Abstract

The beneficial effects of thyroid hormone (TH) on lipid levels are primarily due to its action at the thyroid hormone receptor β (THR-β) in the liver, while adverse effects, including cardiac effects, are mediated by thyroid hormone receptor α (THR-α). A pyridazinone series has been identified that is significantly more THR-β selective than earlier analogues. Optimization of this series by the addition of a cyanoazauracil substituent improved both ...