Publications by authors named "Frank Mennona"

Article Synopsis
  • The thyroid hormone (TH) has beneficial effects on lipid levels via the thyroid hormone receptor β (THR-β) in the liver, while negative effects arise from the thyroid hormone receptor α (THR-α).
  • A newly identified pyridazinone compound, MGL-3196, is significantly more selective for THR-β than previous versions and is 28-fold more selective in functional assays.
  • In studies, MGL-3196 demonstrated excellent safety in rats and healthy volunteers, effectively reducing LDL cholesterol and triglycerides without affecting the central thyroid axis.
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Through high throughput screening and subsequent hit identification and optimization, we synthesized a series of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as the first reported potent and reversible GFAT inhibitors. SAR studies of this class of compounds indicated significant impact on GFAT inhibition potency by substitutions on the A-ring and C-ring. The ketone group was found to be necessary for high potency.

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A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed.

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