89830-71-7

Upstream product

• 41050-96-8 pyridine-4-methylimine acid ethyl ester 
• 2196-13-6 pyridine-4-carbothioamide 
• 100-48-1 pyridine-4-carbonitrile 

Downstream Products

• 1257421-66-1 5,6-bis[(E)-2-(4-methylphenyl)vinyl]-3-pyridin-4-yl-1,2,4-triazine 
• 1257421-68-3 5,6-bis[(E)-2-(3,4-dimethoxyphenyl)vinyl]-3-pyridin-4-yl-1,2,4-triazine 
• 1257421-67-2 5,6-bis[(E)-2-(4-methoxyphenyl)vinyl]-3-pyridin-4-yl-1,2,4-triazine 
• 1257421-65-0 5,6-bis[(E)-2-phenylvinyl]-3-pyridin-4-yl-1,2,4-triazine 
• 1196685-71-8 5,6-bis(4-bromophenyl)-3-(4-pyridyl)-1,2,4-triazine 
• 1196685-72-9 5,6-bis(4-bromophenyl)-2,4'-bipyridine 

Relevant academic research and scientific papers

Preparation method of topiroxostat

The invention provides a preparation method of topiroxostat, and relates to the technical field of medicine synthesis. The preparation method of the topiroxostat comprises the following steps: carrying out heat-preservation stirring reaction on 4-cyanopyridine and hydrazine hydrate in the presence of a solvent and an alkaline reagent to obtain an intermediate 1; carrying out heating stirring reaction on 4-picolinic acid in the presence of an acidic reagent and hydrogen peroxide to obtain isonicotinic acid nitrogen oxide; carrying out heat-preservation stirring reaction on the intermediate 1 and isonicotinic acid nitrogen oxide under the catalysis conditions of a solvent and a condensing agent to obtain an intermediate 3; carrying out heating stirring reaction on the intermediate 3 in the presence of a solvent and cyanide under the protection of nitrogen to obtain an intermediate 4; and carrying out reflux reaction on the intermediate 4 in the presence of an acidic reagent, cooling to room temperature, and filtering to obtain a topiroxostat solid. According to the invention, the topiroxostat is obtained through hydrazinolysis, oxidation, condensation, cyanidation and cyclization, isonicotinic acid and 4-cyanopyridine are selected as starting materials, the preparation method is low in production cost, high in yield, high in purity and few in three wastes, and the preparation method is suitable for industrial production of the topiroxostat and the intermediate thereof.

Synthesis method of topiroxostat

The invention provides a synthesis method of topiroxostat, and relates to the technical field of medicine synthesis. The synthesis method of topiroxostat comprises the steps of carrying out heat-preservation stirring reaction on a raw material 4-cyanopyridine and 80% hydrazine hydrate in the presence of an alcohol solvent and an alkaline reagent, and carrying out post-treatment to obtain an intermediate 1, or carrying out post-treatment under the condition of hydrochloric acid to obtain a hydrochloride form of the intermediate 1; reacting the intermediate 1 or the hydrochloride form of the intermediate 1 with 2-cyano-4-picolinic acid in the presence of a solvent and a condensing agent, and performing post-treatment to obtain an intermediate 2; and heating and refluxing the intermediate 2 for 2-4 hours under the condition of acetic acid, cooling to room temperature, filtering, and carrying out forced air drying to obtain the topiroxostat (crystal form I). The synthesis method has the advantages of low production cost, high yield, high purity and less three wastes, and is suitable for industrial production of topiroxostat and intermediates thereof.

Three-Component Reaction of 3,3-Difluorocyclopropenes, s-Tetrazines, and (benzo) Pyridines

A new three-component reaction leading to 1-α-(pyridyl-2-[1,2,4]triazolyl)-2-alkyl-ethanones has been discovered while studying the reactivity of monosubstituted 3,3-difluorocyclopropenes in an inverse electronic demand Diels-Alder (IEDDA) cycloaddition-cycloreversion sequence with s-tetrazines. The reaction involving the above-mentioned reactants and (benzo)pyridine as a third component results in a complex transformation proceeding in mild conditions in a stoichiometric ratio of reactants and has high functional group tolerance (phenols, amides, ethers, carboxylic acids, ketones, and acrylic esters). As a result, simple pyridines are selectively functionalized at the α-position in good isolated yields. The reaction mechanism includes a rare azaphilic [4 + 2]-cycloaddition step between s-tetrazine and intermediate 1-hydroxyindolizine, suggested after byproduct identification and tracked with a deuterium label. To date, it is only the third known example of skewed azaphilic cycloaddition of tetrazine. The reaction is truly three-component and cannot be effectively performed stepwise.

PYRIDINIUM COMPOUNDS AND THEIR USE AS HERBICIDES

Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.

Topiroxostat and preparation method of intermediate of topiroxostat

4-cyanopyridine is taken as a raw material, a compound III is obtained through a reaction, the compound III and a compound IIB undergo an amidation reaction to obtain a compound IV, and a ring-closurereaction is carried out in the function of an acid catalyst to obtain a target topiroxostat molecule. According to the scheme, the raw materials are cheap and are easy to obtain, the product qualityis high, the reaction is simple to operate and is mild, the yield is high, and the waste gas, waste water and industrial residue are less produced. In the reaction process, nitrogen protection isn't required, and a cyaniding reagent isn't used, so that the method has bright industrial prospects.

Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.

Organic Compound, Benzoxazole Derivative, and Light-Emitting Element, Light-Emitting Device, and Electronic Device Using Benzoxazole Derivative

Novel benzoxazole derivatives are provided to reduce driving voltage of light-emitting elements, and to reduce power consumption of light-emitting elements, light-emitting devices, and electronic devices. A benzoxazole derivative represented by the general formula (G1) is provided. Since the benzoxazole derivative represented by the general formula (G1) has an electron-injecting property, the benzoxazole derivative can be suitably used for light-emitting elements, light-emitting devices, and electronic devices.

ANTI-BACTERIAL COMPOUNDS

Compounds of formula (I), or salts or solvates thereof, in vitro as inhibitors of growth of Gram-positive bacteria, where A is selected from formula (a).

Discovery of a potent phenolic N1-benzylidene- pyridinecarboxamidrazone selective against Gram-positive bacteria

As part of a study into antimycobacterial compounds a set of phenolic N1-benzylidene-pyridinecarboxamidrazones was prepared and evaluated. This report describes the unexpected discovery of a potent compound with a pronounced selectivity for Gram-positive bacteria over Gram-negative micro-organisms. In addition, this compound is active against various drug-resistant Gram-positive bacteria.

Synthesis of 2-pyridylpyridines via aza-Diels-Alder reactions between 3-pyridyl-1,2,4-triazines and some vinyl alkanoates

New synthetic procedure for 2,ω-bipyridines involving aza-Diels-Alder reaction between 3-(ω-pyridyl)-1,2,4-triazine and vinyl octanoate or decanoate as a dienophile is described. Copyright