- Design, synthesis and broad-spectrum Bcr-Abl inhibitory activity of novel thiazolamide-benzamide derivatives
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Bcr-Abl plays an important role in the pathogenesis and development of chronic myeloid leukemia (CML). But Bcr-Abl is prone to mutation, so it increases the difficulty of clinical treatment. Therefore, it is crucial to design a new class of broad-spectrum Bcr-Abl inhibitors. Herein, forty novel thiazolamide-benzamide derivatives were synthesized and evaluated their broad-spectrum Bcr-Abl inhibitory activities. The newly synthesized compounds were characterized by using spectrum data (1H NMR, APCI-MS and IR) and elemental analysis. The protein kinase results indicated that eight compounds (3a, 3e, 3m, 3n, 3p, 4c, 4f, 4g) showed high activities to wild-type and T315I mutation. The most potent compound 3m exhibited an Abl IC50 value as low as 1.273 μM and showed inhibition to the T315I mutant with IC50 value 39.89 μM. 3m could prove to be a new promising lead compound for the further development of broad-spectrum Bcr-Abl inhibitors to overcome clinical acquired resistance.
- Liu, Juan,Huang, Honglin,Deng, Xiangping,Xiong, Runde,Cao, Xuan,Tang, Guotao,Wu, Xin,Xu, Shiyu,Peng, Junmei
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p. 2092 - 2101
(2019/01/26)
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- Synthetic method of 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl) butanone
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The invention discloses a synthetic method of 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl) butanone. The synthetic method comprises the following steps: (1) carrying out a Friedel-Crafts reaction on chlorobenzene with n-butyryl chloride under the catalysis of aluminium trichloride to obtain a compound I; (2) carrying out a bromination reaction on the compound I with bromine under the action ofa catalytic oxidizing agent to obtain a compound II; (3) carrying out a substitution reaction on the compound II with dimethylamine to obtain a compound III; (4) carrying out a quaternization reactionon the compound III with benzyl chloride to obtain a compound IV; (5) carrying out a substitution reaction on the compound IV with morpholine under the action of a composite catalyst to obtain a compound V; and (6) carrying out a rearrangement reaction on the compound V under the action of an alkali so as to obtain the 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl) butanone. The synthetic methodprovided by the invention has the advantages of mild technological condition, simple operation, high selectivity and high total yield.
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- A new amino ketone photoinitiator and in UV - LED light curing system application (by machine translation)
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The invention provides a method suitable for UV - LED light source setting new amino ketone photo initiator, can in long wave zone (365 - 395 nm) has stronger absorption, UV - LED light source is suitable for curing, has overcome the traditional cured high energy consumption, pollution and shortcomings. Electronic unlocalized is good, with strong intramolecular electron transfer performance and excellent photoelectric nature, in the long-wave region 365 nm - 395 nm range have strong absorption, is suitable for high-power UVLED ultraviolet light curing system, compared with the prior art such optical initiator has a considerable advantage. (by machine translation)
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- COMPOUND FOR INHIBITING TYROSINE KINASE ACTIVITY OF DDR2 PROTEIN
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A new furopyrimidine compound, their pharmaceutically acceptable salt, and a tyrosine kinase activity inhibitor. The furopyrimidine compound is a compound defined by chemical formula 1, 2, 3 or 4, on their precursor, and can exist as a form of free base or in an acid-addition salt. Since the furopyrimidine compound has an effect of inhibiting activity of DDR2 tyrosine kinase, it can be used in treating illnesses caused by the DDR2 tyrosine kinase activity such as hepatocirrhosis, rheumatoid arthritis or cancer.
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Page/Page column 28; 31
(2010/02/14)
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- Antifungal azole compounds
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This invention relates to novel antifungal azole compound of the formula: STR1 wherein X and Y are CH or N, R1 is optionally substituted phenyl or phenylalkyl, 1-6C alkyl or 3-8C cycloalkyl, R2 and R3 are hydrogen or 1-6C alkyl, and R4 and R5 are hydrogen, NH2, 1-6C alkyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylamino or alkenyl wherein each alkyl, alkoxy or alkenyl part is of 1-6C, phenyl, phenyl-(1-6C)-alkyl, phenoxy-(1-6C)-alkyl or phenyl-(2-6C)-alkenyl in which the phenyl may be optionally substituted, or a heterocyclyl, (heterocyclyl)-(1-6C)-alkyl or (heterocyclyl)-(2-6C)-alkenyl in each of which the heterocyclyl ring may be optionally substituted, provided at least one of R2, R3, R4 and R5 is other than hydrogen, and the acid addition salts of those compounds which contain a basic nitrogen; together with processes for their manufacture; compositions containing them; and a method of combatting plant fungal diseases.
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