100791-00-2

Upstream product

• 10177-29-4 4-chloronicotinic acid 

Downstream Products

• 1415407-64-5 C₂₅H₂₃Cl₂N₃O₂ 
• 1415407-63-4 C₂₄H₂₁Cl₂N₃O₂ 
• 1315468-79-1 [4-(2,5-dichloro-4-bromophenoxy)pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)methanone 
• 1415407-62-3 C₂₆H₂₇N₃O₂ 
• 1415407-61-2 C₂₃H₁₈Cl₃N₃O₂ 
• 1415407-60-1 TC-G-1005 
• 1415407-59-8 C₂₄H₂₃N₃O₂ 
• 1415407-58-7 C₂₅H₂₅N₃O₄ 
• 1415407-57-6 C₂₄H₂₃N₃O₃ 
• 1415407-56-5 C₂₃H₂₀ClN₃O₂ 
• 1415407-55-4 C₂₃H₂₀ClN₃O₂ 
• 1415407-54-3 C₂₃H₂₁N₃O₂ 
• 1415407-53-2 C₂₄H₂₁Cl₂N₃O₂ 
• 1315468-57-5 [4-(2,5-dichlorophenoxy)pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)methanone 

Relevant academic research and scientific papers

Discovery of pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives as a new class of histone lysine demethylase 4D (KDM4D) inhibitors

Herein we report the discovery of a series of new small molecule inhibitors of histone lysine demethylase 4D (KDM4D). Molecular docking was first performed to screen for new KDM4D inhibitors from various chemical databases. Two hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the more selective one, compound 2, which led to the discovery of several new KDM4D inhibitors. Among them, compound 10r is the most potent one with an IC50 value of 0.41?±?0.03?μM against KDM4D. Overall, compound 10r could be taken as a good lead compound for further studies.

Catalyst-controlled switch in chemo- and diastereoselectivities: Annulations of morita-baylis-hillman carbonates from isatins

Regulating both the chemo- and diastereoselectivity, divergently, of a reaction is highly attractive but extremely challenging. Presented herein is a catalyst-controlled switch in the chemo- and diastereodivergent annulation reactions of Morita-Baylis-Hillman carbonates, derived from isatins and 2-alkylidene-1H-indene-1,3(2H)-diones, in exclusive α-regioselectivity. α-Isocupreine efficiently catalyzed [2+1] reactions to access cyclopropane derivatives, and the diastereodivergent [3+2] annulations were accomplished by employing either a chiral phosphine or a DMAP-type molecule. All reactions exhibited excellent chemoselectivities, and good to remarkable stereoselectivities were furnished, thus leading to a collection of compounds with skeletal and stereogenic diversity. Moreover, DFT computational calculations elucidated the catalyst-based switch in mechanism.

Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease

The reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID-19) and other diseases. We report structure-activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of Mpro, particularly with respect to improved selectivity.

HINDERED DISULFIDE DRUG CONJUGATES

The invention relates generally to disulfide drug conjugates wherein a linker comprising a sulfur-bearing carbon atom substituted with at least one hydrocarbyl or substituted hydrocarbyl is conjugated by a disulfide bond to a cysteine sulfur atom of a targeting carrier, and wherein the linker is further conjugated to a drug moiety. The invention further relates to activated linker-drug conjugates suitable for conjugation to a targeting carrier by a disulfide bond. The invention further relates to methods for preparing hindered disulfide drug conjugates.

Benzoisothiazolone organo/copper-cocatalyzed redox dehydrative construction of amides and peptides from carboxylic acids using (EtO)3P as the reductant and O2 in air as the terminal oxidant

Carboxylic acids and amine/amino acid reactants can be converted to amides and peptides at neutral pH within 5-36 h at 50 °C using catalytic quantities of a redox-active benzoisothiazolone and a copper complex. These catalytic "oxidation-reduction condensation" reactions are carried out open to dry air using O2 as the terminal oxidant and a slight excess of triethyl phosphite as the reductant. Triethyl phosphate is the easily removed byproduct. These simple-to-run catalytic reactions provide practical and economical procedures for the acylative construction of C-N bonds.

Discovery of intestinal targeted TGR5 agonists for the treatment of type 2 diabetes

Activation of TGR5 stimulates intestinal glucagon-like peptide-1 (GLP-1) release, but activation of the receptors in gallbladder and heart has been shown to cause severe on-target side effects. A series of low-absorbed TGR5 agonists was prepared by modify

ARYL ETHER-BASE KINASE INHIBITORS

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

SPECIFIC CARBOXAMIDES AS KCNQ2/3 MODULATORS

The invention relates to specific carboxamides of formula (I) as KCNQ2/3 modulators, to processes for their preparation, to medicaments comprising these compounds and to the use of these compounds in the preparation of medicaments.

SPECIFIC CARBOXAMIDES AS KCNQ2/3 MODULATORS

The invention relates to specific carboxamides, to processes for their preparation, to medicaments comprising these compounds and to the use of these compounds in the preparation of medicaments.

4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists

A series of 4-benzofuranyloxynicotinamide derivatives were identified to be novel, potent, and orally available TGR5 agonists. Among them, compound 9r had the highest potency in vitro (hTGR5 EC50 = 0.28 nM, mTGR5 EC 50 = 0.92 nM). Further in vivo studies disclosed that 9r could effectively lower the blood glucose, but meantime caused an increase in the gallbladder volume of mice. Subsequent research toward eliminating the gallbladder toxicity resulted in compound 19 with low permeability. Although the EC50 of mTGR5 of 19 was larger one order than that of 9r, it still had good glucose-lowing activity. Nevertheless, 19 also caused the adverse effects to the gallbladder. The drug levels detection disclosed that the concentration of 19 was only lower than that of 9r in plasma but was higher in bile and gallbladder tissue. This result indicated that low exposure in plasma could not guarantee low exposure in bile and gallbladder tissue, and thus resulting in the gallbladder toxicity of 19.