- INHIBITORS OF ENL/AF9 YEATS
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Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.
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Paragraph 00311; 00314-00315; 00324-00325
(2021/06/26)
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- Method for preparing 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid
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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.
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- RHO KINASE INHIBITORS
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The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1 and X are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of Rho Kinase-mediated disorders selected from hypertension, atherosclerosis, restenosis, stroke, myocardial infarction, heart failure, coronary artery disease, peripheral artery disease, coronary vasospasm, cerebral vasospasm, ischemia/reperfusion injury, pulmonary hypertension, angina, erectile dysfunction, renal disease, organ failure, asthma, glaucoma, cancer, Alzheimer's disease, multiple sclerosis, spinal cord injury, neuropathic pain, rheumatoid arthritis, psoriasis inflammatory bowel disease, and combinations of such disorders.
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Page/Page column 88
(2012/02/01)
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- N1/N2-Lactam Acetyl-CoA carboxylase inhibitors
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal
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Page/Page column 41
(2012/05/07)
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- N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions there-of; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal
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Page/Page column 14
(2011/05/16)
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- N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal.
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Page/Page column 27
(2011/06/16)
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