William N. Washburn

TL;DR: Novel thyroid receptor ligands are provided having the general formula I wherein X, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12. and R13 are as defined herein this paper.

TL;DR: The investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy.

TL;DR: An assessment of the biliary toxicity risk of this compound rendered this compound non-progressible, and an optimized lead from this series, rMCHR1 Ki=1.8 nM, demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model.

TL;DR: H hepatobiliary injury by thienopyrimidinone MCHR1 antagonists was driven through a CYP-mediated bioactivation pathway, suggesting that injury of biliary epithelium may be the first step toward an adaptive proliferative response causing BDH by these compounds.

TL;DR: In this article, the authors present a method for treating a patient suffering from an MCHR-1 modulated disease or disorder such as obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.