444663-80-3

Upstream product

• 74896-66-5 Methyl 3,5-Dibromo-4-methylbenzoate 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 

Downstream Products

• 444663-82-5 3,5-dibromo-4-[(4-methoxy-benzylamino)-methyl]-benzoic acid methyl ester 
• 444665-91-2 methyl 3,5-dibromo-4-formylbenzoate 
• 444666-01-7 methyl 3,5-dibromo-4-(hydroxymethyl)benzoate 
• 920509-59-7 (3,5-dibromo-4-bromomethylphenyl)methanol 
• 920509-64-4 [3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-ylmethyl)phenyl]acetonitrile 
• 920509-63-3 6-(2,6-dibromo-4-(chloromethyl)benzyl)-4-isopropylpyridazin-3(2H)-one 
• 920509-62-2 (6-chloro-5-isopropylpyridazin-3-yl)[2,6-dibromo-4-(tetrahydropyran-2-yloxymethyl)phenyl]acetonitrile 
• 920509-60-0 (2,6-dibromo-4-hydroxymethylphenyl)acetonitrile 
• 920509-61-1 [2,6-dibromo-4-(tetrahydropyran-2-yloxymethyl)phenyl]acetonitrile 
• 444663-83-6 3,5-dibromo-4-[3-(2,6-dichloro-phenyl)-1-(4-methoxy-benzyl)-ureidomethyl]-benzoic acid methyl ester 

Relevant academic research and scientific papers

Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells

In pursuit of fast bioorthogonal reactions, reactive moieties have been increasingly employed for selective labeling of biomolecules in living systems, posing a challenge in attaining reactivity without sacrificing selectivity. To address this challenge, here we report a bioinspired strategy in which molecular shape controls the selectivity of a transient, highly reactive nitrile imine dipole. By tuning the shape of structural pendants attached to the ortho position of the N-aryl ring of diaryltetrazoles-precursors of nitrile imines, we discovered a sterically shielded nitrile imine that favors the 1,3-dipolar cycloaddition over the competing nucleophilic addition. The photogenerated nitrile imine exhibits an extraordinarily long half-life of 102 s in aqueous medium, owing to its unique molecular shape that hinders the approach of a nucleophile as shown by DFT calculations. The utility of this sterically shielded nitrile imine in rapid (～1 min) bioorthogonal labeling of glucagon receptor in live mammalian cells was demonstrated.

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 highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia

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 the potency and selectivity and led to MGL-3196 (53), which is 28-fold selective for THR-β over THR-α in a functional assay. Compound 53 showed outstanding safety in a rat heart model and was efficacious in a preclinical model at doses that showed no impact on the central thyroid axis. In reported studies in healthy volunteers, 53 exhibited an excellent safety profile and decreased LDL cholesterol (LDL-C) and triglycerides (TG) at once daily oral doses of 50 mg or higher given for 2 weeks.

PYRIDAZINONE DERIVATIVES AS THYROID HORMONE RECEPTOR AGONISTS

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto.

(Halo-benzo carbonyl)heterocyclo fused phenyl p38 kinase inhibiting agents

Compounds described by the chemical formula (I) or a pharmaceutically acceptable salt thereof: are inhibitors of p38 useful in the treatment of inflammatory diseases such as arthritis.

Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase

The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38α MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38α inhibitor reported by Merck Research Laboratories and VX-745. O