106778-42-1Relevant articles and documents
Discovery of 2-substituted-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide as potent and selective protein arginine methyltransferases 5 inhibitors: Design, synthesis and biological evaluation
Shao, Jingwei,Zhu, Kongkai,Du, Daohai,Zhang, Yuanyuan,Tao, Hongrui,Chen, Zhifeng,Jiang, Hualiang,Chen, Kaixian,Luo, Cheng,Duan, Wenhu
, p. 317 - 333 (2019/01/04)
Protein arginine methyltransferases 5 (PRMT5) represents an attractive drug target in epigenetic field for the treatment of leukemia and lymphoma. Here, a series of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)amide derivatives targeting PRMT5 were designed with structure-based approach and synthesized. Among them, compound 46 showed potent and selective PRMT5 inhibition activity with an IC50 of 8.5 nM, which was approximately equivalent with the phase I clinical trial PRMT5 inhibitor GSK-3326595 (IC50 = 5.5 nM). Compound 46 also displayed pronounced anti-proliferative activity in MV4-11 cells (GI50 = 18 nM) and antitumor activity in MV4-11 mouse xenografts model. This molecule can serve as an excellent tool compound for probing the biological function of PRMT5.
Preparation method of 1-aminoisoquinoline-6-methanol
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Paragraph 0020; 0023, (2017/08/29)
The invention relates to a synthesis method of 1-aminoisoquinoline-6-methanol. The synthesis method comprises the following steps: reacting 6-bromoisoquinoline used as a raw material to form 6-cyanoisoquinoline; adding a sulfuric acid solution to obtain isoquinoline-6-carboxylic acid; further obtaining isoquinoline-6-methyl formate under the action of absolute methanol and thionyl chloride; further adding m-chloroperoxybenzoic acid in batches in dichloromethane, and reacting to obtain a mixture isoquinoline-6-methyl formate oxynitride; adding into phosphorus oxychloride in batches, cooling after the reaction is completed, pouring into cracked ice, and precipitating a solid 1-chloroisoquinoline-6-methyl formate crude product; directly extracting the water phase with ethyl acetate, and performing centrifugal drying to obtain another 1-chloroisoquinoline-6-methyl formate crude product; merging the crude products of two batches, passing through a silica gel column, and eluting to obtain 1-chloroisoquinoline-6-methyl formate; adding into tetrahydrofuran, then cooling to -30 DEG C, and adding lithium aluminum hydride in batches to obtain a 1-(1-chloroisoquinoline-6-yl)methanol product; mixing with p-methoxybenzylamine, and heating to obtain (1-(4-methoxybenzylamino)isoquinoline-6-yl)methanol; and adding into trifluoroacetic acid, and refluxing to obtain the final product 1-aminoisoquinoline-6-methanol. The method is reasonable in route, low in waste, high in yield and easy to operate, and realizes raw material saving.
NOVEL DIHYDROPYRIMIDIN-2(1H)-ONE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Page/Page column 157, (2011/04/24)
The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.