409366-27-4

Upstream product

• 67-56-1 methanol 
• 89894-49-5 (3,5-dichloro-4-hydroxyphenyl)acetic acid 
• 156-38-7 4-hydroxyphenylacetate 
• 14199-15-6 Methyl 4-hydroxyphenylacetate 
• 788824-07-7 C₁₄H₁₆Cl₂O₅ 
• 59595-92-5 chlorure de dichloro-3,5 hydroxy-4 benzoyle 
• 3336-41-2 3,5-dichloro-4-hydroxybenzoic acid 

Downstream Products

• 88381-43-5 4-hydroxy-3,5-dichlorophenylacetamide 
• 725239-75-8 [3,5-dichloro-4-(4-methoxy-phenoxy)-phenyl]-acetic acid methyl ester 
• 725239-76-9 [4-(4-benzyloxy-phenoxy)-3,5-dichloro-phenyl]-acetic acid methyl ester 
• 868730-14-7 (3,5-dichloro-4-trifluoromethanesulfonyloxy-phenyl)-acetic acid methyl ester 
• 788824-08-8 [3,5-dichloro-4-(3-formyl-4-methoxy-phenoxy)-phenyl]-acetic acid methyl ester 
• 788824-22-6 [4-(3-bromo-4-methoxy-phenoxy)-3,5-dichloro-phenyl]-acetic acid methyl ester 
• 788824-09-9 5-(2,6-dichloro-4-methoxycarbonylmethyl-phenoxy)-2-hydroxy-benzoic acid 
• 788824-21-5 [3,5-dichloro-4-(6-methoxy-biphenyl-3-yloxy)-phenyl]-acetic acid methyl ester 

Relevant academic research and scientific papers

THYROID HORMONE RECEPTOR AGONISTS

Provided herein are novel thyroid hormone receptor (TR) agonists, e. g., having Formula I, II, or III. Also provided are methods of preparing the novel TR agonists and method of using the novel TR agonists for treating diseases or disorder modulated by TR agonists, such as NAFLD, NASH, diabetes, hyperlipidemia and/or hypercholesterolemia.

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.

Synthesis of (+)-O-methylthalibrine by employing a stereocontrolled Bischler-Napieralski reaction and an electrochemically generated diaryl ether

An efficient electrochemical four-step route was developed for the preparation of diaryl ether derivatives by using halogenation and dehalogenation processes in addition to electrochemical phenolic oxidation and reduction reactions. The synthesis of (+)-O

Electrochemical construction of the diaryl ethers: A synthetic approach to o-methylthalibrine

Electrochemical dimerization of halogenated p-hydroxyphenylacetic acid derivatives followed by Zn reduction provided the corresponding diaryl ethers. Manipulation of the reduction step using several procedures increased its efficiency, which enabled the construction of o-methylthalibrine, an isoquinoline-class alkaloid.

THYROID RECEPTOR LIGANDS

Thyroid receptor ligands are provided which have the general formula I wherein: R1 is R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, provided that at

Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin

As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3- methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with Ki (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6′-iodononivamide.

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.

Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta

A set of thyromimetics having improved selectivity for TR-β1 were prepared by replacing the 3′-isopropyl group of 2 and 3 with substituents having increased steric bulk. From this limited SAR study, the most potent and selective compounds ident