6959-48-4Relevant articles and documents
Synthesis method of 3-chloromethylpyridine hydrochloride
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Paragraph 0020; 0024; 0025; 0029; 0030; 0034, (2020/05/05)
The invention belongs to the field of organic chemistry, and specifically relates to a synthesis method of 3-chloromethylpyridine hydrochloride. The synthesis method comprises the following steps: (1)taking 3-methylpyridine as a raw material and water as a solvent, oxidizing 3-methylpyridine into 3-picolinic acid by potassium permanganate, wherein the molar ratio of 3-methylpyridine to potassiumpermanganate is 1: (2.1-2.3); maintaining the oxidation temperature in a range of 85-90 DEG C, heating for 30 minutes, adjusting the reaction liquid to be acidic after the reaction is finished, and then cooling and filtering to obtain 3-picolinic acid; (2) generating methyl 3-picolinate from 3-picolinic acid and methanol under an acidic condition, wherein the molar ratio of 3-picolinic acid to methanol is 1: 1.3; (3) reducing methyl 3-picolinate into 3-pyridylcarbinol; and (4) reacting the 3-pyridylcarbinol with thionyl chloride to obtain the target product 3-chloromethylpyridine hydrochloride, wherein the molar ratio of the 3-pyridylcarbinol to the thionyl chloride is 1: (1.1-1.3).
PYRIMIDINE AND PYRAZINE HDAC1,2 INHIBITORS
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Page/Page column 37, (2020/05/19)
Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity.
A 3 - chloromethyl pyridine hydrochloride synthetic method
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, (2019/05/28)
The invention belongs to the field of organic chemistry, and in particular relates to a 3 - chloromethyl pyridine hydrochloride synthetic method, comprises the following steps: (1) to 3 - methyl pyridine as raw materials, takes water as a solvent, the potassium permanganate oxide it to 3 - pyridine carboxylic acid, wherein 3 - methyl pyridine with potassium permanganate in a molar ratio of 1: 2.1 - 2.3, the oxidation temperature to maintain the 85 - 90 °C, heating 30 min, the reaction end the reaction liquid is adjusted to be acidic, and then cooling and filtering to obtain 3 - pyridine carboxylic acid; (2) 3 - pyridine carboxylic acid with methanol under acidic conditions to produce the 3 - pyridine carboxylic acid methyl ester, wherein the 3 - pyridine carboxylic acid with methanol in a molar ratio of 1: 1.3; (3) reducing 3 - pyridine carboxylic acid methyl ester as the 3 - pyridine methanol; (4) 3 - pyridine methanol with thionyl chloride reaction to obtain the target product 3 - chloromethyl pyridine hydrochloride, 3 - pyridine methanol with thionyl chloride in a molar ratio of 1: 1.1 - 1.3.
Synthesis method of 3-picolyl chloride hydrochloride
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Paragraph 0020; 0021; 0023; 0024; 0025; 0026; 0027, (2018/09/11)
The invention belongs to the field of organic chemistry and discloses a synthesis method of 3-picolyl chloride hydrochloride. The synthesis method comprises the following steps: taking 3-methyl pyridine as a raw material, controlling the temperature is to be 0-40 DEG C, introducing dry hydrogen chloride gas during stirring under normal pressure; stopping stirring after all the raw materials form white solid hydrochloride, continuing introducing hydrogen chloride gas, and dissolving the solid until a liquid 3-methyl pyridine hydrochloride is formed; taking the hydrochloride as a raw material, controlling the temperature to be 110-150 DEG C, introducing chlorine gas until the ratio of the 3-methyl pyridine to 3-chloromethyl pyridine is 45:55-55:45, and stopping introducing chlorine; and carrying out reduced pressure distillation on the reaction liquid to distill out unreacted 3-methylpyridine to obtain the 3-picolyl chloride hydrochloride. The synthesis method provided by the invention has the advantages of high yield, short reaction time, simple and reliable technology and high economy, and is suitable for industrial large-scale production.
Tetrazolylhydrazides as selective fragment-like inhibitors of the JumonjiC-domain-containing histone demethylase KDM4A
Rüger, Nicole,Roatsch, Martin,Emmrich, Thomas,Franz, Henriette,Schüle, Roland,Jung, Manfred,Link, Andreas
supporting information, p. 1875 - 1883 (2015/11/10)
The JumonjiC-domain-containing histone demethylase 2A (JMJD2A, KDM4A) is a key player in the epigenetic regulation of gene expression. Previous publications have shown that both elevated and lowered enzyme levels are associated with certain types of cancer, and therefore the definite role of KDM4A in oncogenesis remains elusive. To identify a novel molecular starting point with favorable physicochemical properties for the investigation of the physiological role of KDM4A, we screened a number of molecules bearing an iron-chelating moiety by using two independent assays. In this way, we were able to identify 2-(1H-tetrazol-5-yl)acetohydrazide as a novel fragment-like lead structure with low relative molecular mass (Mr=142 Da), low complexity, and an IC50 value of 46.6 μm in a formaldehyde dehydrogenase (FDH)-coupled assay and 2.4 μm in an antibody-based assay. Despite its small size, relative selectivity against two other demethylases could be demonstrated for this compound. This is the first example of a tetrazole group as a warhead in JMJD demethylases. Anchor fragment: To develop non-promiscuous metalloenzyme inhibitors, a metal-complexing acetohydrazide group was integrated in a tetrazolyl fragment, which can be matured into a scaffold to promote further selectivity at the ligand backbone binding site of these emerging drug targets.
Inhibitors of protein kinases
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, (2011/10/04)
Compounds of general Formula (I): wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.
