- Growth Factor Receptor antagonists. Preparation method and application thereof
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The invention relates to a small molecule antagonist for transforming growth factor β receptors, a method for preparing the small molecule antagonist, and application of the small molecule antagonist in preparation of drugs. The small molecule antagonist for transforming the growth factor β receptor has the application of treating and/or preventing various diseases mediated by ALK5, and has great clinical application potential.
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Paragraph 0093-0098
(2021/11/10)
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- Discovery of Carbono(di)thioates as Indoleamine 2,3-Dioxygenase 1 Inhibitors
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A structure-activity relationship study unexpectedly showed that carbonothioates 4a and 4b, obtained by a unique alkaline hydrolysis of 2-alkylthio-oxazolines 3a and 3b, respectively, are a novel scaffold for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. Derivatization of the carbonothioates enhanced inhibitory activity against IDO1 and cellular kynurenine production without cytotoxicity and led to the discovery of the related scaffolds carbonodithioates 5 and cyanocarbonimidodithioates 6 as IDO1 inhibitors. Incorporation of an OH group provided the most potent analogue 5i. UV-visible absorption spectroscopy of the Soret band, as well as docking and peptide mapping studies, suggested that these molecules bind to the heme in the active site of IDO1. Our unique IDO1 inhibitors are potential leads for future development.
- Kumazawa, Miyuki,Tejima, Manabu,Fukuda, Miwa,Takeda, Shota,Suzuki, Kenji,Mizumoto, Yukiko,Sato, Kakeru,Waki, Minoru,Miyachi, Hiroyuki,Asai, Akira,Takikawa, Osamu,Hashimoto, Tomoko,Ohno, Osamu,Matsuno, Kenji
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supporting information
p. 211 - 216
(2021/02/01)
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- Synthesis method of ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate
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The invention belongs to the technical field of pharmaceutical intermediates, and relates to a synthesis method of ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate. The method includes the followingsteps that an aqueous solution of cyanamide is mixed with ethanol, carbon disulfide and a potassium hydroxide solution are added for reaction, and a precipitated solid is subjected to suction filtration and drying to obtain an intermediate A; the intermediate A is dissolved in a mixed solution of ethanol and water, an iodomethane ethanol solution is dropped for reaction, and an intermediate B isobtained through concentration and drying; the intermediate B, ethyl chloroacetate and triethylamine are subjected to a reflux reaction in ethanol, and the obtained solution is concentrated, washed and re-crystallized to obtain ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate. The cost of raw materials is low, the yield of by-products is low, the product yield is high, and the method is suitablefor scale-up production.
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Paragraph 0032; 0034
(2019/11/20)
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- HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES
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The invention relates to compounds of Formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases in which ALK protein is involved or in which inhibition of ALK activity may induce benefit, especially for the treatment of cancer mediated by a mutated EML4-ALK fusion protein.
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Page/Page column 120-121
(2011/11/30)
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