IDO restrainer containing (E)-4-(beta-bromo vinyl)benzoyloxy structure

Abstract

The invention belongs to the technical field of new drug synthesis, and in particular relates to an IDO inhibitor containing (E)-4-(beta-bromovinyl)phenoxy acyl structure, as well as a preparation method thereof. The preparation method comprises the following steps: solvent benzene, (E)-4-(beta-bromovinyl) phenol, carboxylic acid and p-dimethylaminopyridine are added to a flask respectively and magnetically stirred for 5 to 20 minutes at room temperature; then N, N'-dicyclohexylcarbodiimide is added and reacts for 2 to 24 hours at room temperature; after the reaction is completed, the solvent benzene is steamed off after decompression; residue is subjected to column chromatography separation and purification by taking ethyl acetate / petroleum ether as leacheate, and then a needed product can be obtained, wherein the molar ratio of the solvent benzene to the (E)-4-(beta-bromovinyl) phenol is 50-200:1; the molar ratio of the carboxylic acid to the (E)-4-(beta-bromovinyl) phenol is 1-1.5:1; the molar ratio of the p-dimethylaminopyridine to the (E)-4-(beta-bromovinyl) phenol is 0.1-1.5:1; and the molar ratio of the N, N'-dicyclohexylcarbodiimide to the (E)-4-(beta-bromovinyl) phenol is 1-1.2:1. The method takes the (E)-4-(beta-bromovinyl) phenol as a synthesis building block and obtains a series of the novel IDO inhibitors containing the (E)-4-(beta-bromovinyl)phenoxy acyl structure through esterification reaction, and the IDO inhibitors can be used for treating the diseases with the pathological features of IDO mediated tryptophan metabolic pathway.

Description

technical field

[0001] The invention belongs to the technical field of new drug synthesis, and in particular relates to an IDO inhibitor containing (E)-4-(β-bromovinyl)phenoxyacyl structure and a preparation method thereof. Background technique

[0002] Indoleamine-2,3-dioxygenase (IDO; MW 48,000; EC 1.13.11.42) is a heme-containing enzyme that is the first and rate-limiting enzyme in mammalian tryptophan metabolism . IDO catalyzes the oxidation of the essential amino acid tryptophan to N-formylkynurenine via dioxygen and is responsible for the disposal of tryptophan in the human body. General inhibitors of heme-containing enzymes are known to inhibit IDO in a non-specific manner. In addition, certain tryptophan (substrate) analogs such as 1-methyl-L-tryptophan (1MT) and β-(3-benzofuryl)-DL-alanine are competitive for IDO Inhibitors (Cady, S.G. and Sono, M. Arch. Biochem. Biophys. 1991 291, 326).

[0003] Interferon gamma is one of several potential inducers of IDO expre...

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