205055-63-6Relevant articles and documents
RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING SAME, AND USE THEREOF
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Paragraph 0228-0232, (2022/01/12)
A Rho-associated protein kinase (ROCK) inhibitor represented by formula (I), a pharmaceutical composition comprising same, and a use thereof for preventing or treating ROCK-mediated diseases.
The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu4 PAM development candidate
Panarese, Joseph D.,Engers, Darren W.,Wu, Yong-Jin,Guernon, Jason M.,Chun, Aspen,Gregro, Alison R.,Bender, Aaron M.,Capstick, Rory A.,Wieting, Joshua M.,Bronson, Joanne J.,Macor, John E.,Westphal, Ryan,Soars, Matthew,Engers, Julie E.,Felts, Andrew S.,Rodriguez, Alice L.,Emmitte, Kyle A.,Jones, Carrie K.,Blobaum, Anna L.,Jeffrey Conn,Niswender, Colleen M.,Hopkins, Corey R.,Lindsley, Craig W.
, p. 342 - 346 (2018/12/05)
This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu4 positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled a
Method for preparing 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid
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, (2017/08/29)
The invention relates to a method for synthesizing 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid. The 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid is made of 6-bromoisoquinoline. The method includes adding meta-chloroperoxybenzoic acid into the 6-bromoisoquinoline and carrying out reaction on the 6-bromoisoquinoline and the meta-chloroperoxybenzoic acid under room-temperature conditions overnight to obtain a mixture which is bromoisoquinoline nitrogen oxide; adding the mixture into phosphoryl chloride in batches, carrying out temperature reaction on the mixture and the phosphoryl chloride to obtain reaction products, cooling the reaction products to precipitate a large quantity of solid and washing and drying the solid to obtain 6-bromine-1-chloroisoquinoline; extracting aqueous phases and directly carrying out spin dry on organic phases to obtain 6-bromine-1-chloroisoquinoline with the purity higher than 95%; placing the 6-bromine-1-chloroisoquinoline into THF (tetrahydrofuran) and adding n-butyl lithium and carbon dioxide gas into the 6-bromine-1-chloroisoquinoline and the THF to obtain 1-chloroisoquinoline-6-formic acid; placing the 1-chloroisoquinoline-6-formic acid into concentrated hydrochloric acid to obtain white solid which is 1-oxo-1, 2-dihydroisoquinolines-6-formic acid; placing the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid into solvents, adding cesium carbonate into the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid and the solvents and dropwise adding methyl iodide into the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid and the solvents to obtain 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate; adding the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate into methyl alcohol, adding NaOH solution into the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate and the methyl alcohol, removing the methyl alcohol by means of reduced-pressure distillation to obtain mixtures, regulating the PH (potential of hydrogen) of the mixtures until the PH of the mixtures is equal to 2, precipitating solid, carrying out suction filtration and washing and drying the solid to obtain a product which is the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid. The method has the advantages of reasonable route, little wastage, high yield, easiness in operation and capability of saving raw materials.
