32852-92-9Relevant articles and documents
Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents
Kar, Sidhartha S.,Bhat, Varadaraj,Rao, Praveen P. N.,Shenoy, Vishnu P.,Bairy, Indira,Shenoy, G. Gautham
, p. 2299 - 2310 (2016)
A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 μg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.
Preparation method of roxadustat intermediate
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Paragraph 0014; 0031-0042, (2021/07/08)
The invention discloses a preparation method of a roxadustat intermediate, which comprises the following steps of: firstly, reacting methyl nitroacetate with trimethyl orthoformate to obtain a product I, and performing catalytic hydrogenation reduction to obtain a product II; then reacting the product II with m-phenoxyacetophenone to obtain a product III; carrying out a Pomeranz-Fritsch reaction on the product III, and completing intramolecular ring closing to obtain a product IV; finally, carrying out an oxidation reaction on the product IV to obtain the roxadustat intermediate 1-methyl-4-hydroxy-7-phenoxy isoquinoline-3-methyl carboxylate. According to the preparation method of the roxadustat intermediate, the raw materials are easy to obtain, and the production cost can be remarkably reduced. The whole process is simple, the whole consumed time is short, the production efficiency is high, the yield is high, the reaction condition is mild, the post-treatment is simple and convenient, and the method is suitable for large-scale preparation and has a great application prospect.
Novel method for high-yield preparation of roxadustat intermediate
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Paragraph 0042-0045, (2021/08/14)
The invention discloses a preparation method of a roxadustat intermediate. The preparation method comprises the following steps: (1) subjecting a compound 1 and a compound 2 to reacting in an organic solvent under the catalysis of alkali to obtain an intermediate 3; (2) reducing the intermediate 3 in an organic solvent through a reducing agent to obtain an intermediate 4; (3) subjecting the intermediate 4 to reacting with a bromination reagent in an organic solvent to obtain an intermediate 5; (4) subjecting the intermediate 5 to reacting with a compound 6 in an organic solvent under the catalysis of acid to obtain an intermediate 7; (5) carrying out a cyclization reaction on the intermediate 7 in an organic solvent and a catalytic system to prepare an intermediate 8; and (6) subjecting the intermediate 8 to reacting in an organic solvent through a dehydrogenation reagent to obtain the roxadustat intermediate 9. The preparation method of the roxadustat intermediate has the advantages that raw materials are easy to obtain, operation steps are few, a process is simple, reaction yield is high, an atom utilization rate is high, and industrial production is easy.
Method suitable for industrial production of roxadustat intermediate
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Paragraph 0039-0042, (2021/09/04)
The invention discloses a preparation method of a roxadustat intermediate. 4-hydroxy-1-methyl-7-phenoxy-3-isoquinoline carboxylic ester (IV) is a key intermediate for preparing roxadustat. The preparation method comprises the steps of (1) reacting a compound I and a compound II in an organic solvent under the catalysis of acid to prepare an intermediate III; and (2) carrying out cyclization reaction on the intermediate III in an organic solvent and a catalytic system to prepare the roxadustat intermediate IV. The preparation method of the roxadustat intermediate has the advantages that the raw materials are easy to obtain, the operation steps are few, the process is simple, the reaction yield is high, the atom utilization rate is high, and industrial production is easy.
Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy
Chen, Hekai,Kong, Jun,Li, Tian,Xu, Qun,Yin, Hang,Zhang, Liwei
supporting information, p. 1771 - 1779 (2021/11/19)
In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 001063; 001064, (2018/07/29)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
Method for preparing Roxadustat intermediate
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Paragraph 0035; 0036, (2017/08/28)
The invention provides a preparation method of Roxadustat intermediate 4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinecarboxylate (IV), comprising the step of subjecting 2-(1-(3-phenoxyphenyl)ethylimide)dimalonate (III) as a starting material to condensation and cyclization. The preparation method of the Roxadustat intermediate IV has the advantages that material is easy to obtain, operating steps are few, the process is simple, the reaction yield is high, atom utilization rate is high, and the method is easy for industrial production. The reaction general formula is shown in the specification.
Green alternative solvents for the copper-catalysed arylation of phenols and amides
Sambiagio, Carlo,Munday, Rachel H.,John Blacker,Marsden, Stephen P.,McGowan, Patrick C.
, p. 70025 - 70032 (2016/08/06)
Investigation of the use of green organic solvents for the Cu-catalysed arylation of phenols and amides is reported. Alkyl acetates proved to be efficient solvents in the catalytic processes, and therefore excellent alternatives to the typical non-green solvents used for Cu-catalysed arylation reactions. Solvents such as isosorbide dimethyl ether (DMI) and diethyl carbonate also appear to be viable possibilities for the arylation of phenols. Finally, a novel copper catalysed acyl transfer process is reported.
METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF
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Paragraph 00468, (2016/01/01)
Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.
Picolinamides as effective ligands for copper-catalysed aryl ether formation: Structure-activity relationships, substrate scope and mechanistic investigations
Sambiagio, Carlo,Munday, Rachel H.,Marsden, Stephen P.,Blacker, A. John,McGowan, Patrick C.
supporting information, p. 17606 - 17615 (2015/02/05)
The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end-of-life Cu species were isolated and identified as CuII complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper-based chemistry.
