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.
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.
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.