Abstract: Benzoxaborole structure contains a phenyl ring fused with a heterocyclic oxaborole ring moiety. Benzoxaboroles are considerably more stable and exhibit high hydrolytic resistance compared with corresponding phenylboronic acids. The enhanced acidity of benzoxaboroles allows them to be predominantly in anionic forms in aqueous solution at physiological pH, which causes them to exhibit higher water solubility and better pharmacokinetic properties than phenylboronic acids. Increasing interest in benzoxaborole compounds is mainly due to their broad-spectrum biological activity including antimicrobial, anti-inflammatory and other medicinal properties. Quinoline is a highly privileged nitrogen containing a bicyclic ring system where a benzene ring is fused to a pyridine ring. The quinoline moiety is found in many natural products and has been traditionally used as a medicine for treating a wide variety of diseases. Quinoline-based molecules have been found to exhibit a diverse range of pharmacological properties with uses as antimalarial, antibacterial, anticonvulsant, cardiotonic, anticancer, anthelmintic, antifungal, anti-inflammatory and analgesic agents.
In this regard, we envisioned that introduction of aminobenzoxaborole unit on quinolines would result in novel molecular entities with favorable pharmacological and pharmaceutical properties for developing therapeutic agents for a wide variety of diseases. The aims of the current work include: 1) Develop a new synthetic methodology for the rapid creation of aminobenzoxaborole containing quinolines; and 2) Explore the efficacy of synthesized candidate compounds as antibacterial, antifungal, antiviral, antiinflammatory, and antimalarial agents.
As a part of this thesis, we developed a novel synthetic methodology for preparing quinolino aminobenzoxaboroles. The synthesized compounds were initially evaluated for their cytotoxic properties against various human and murine proliferating cancer cells. All the compounds were found to be well tolerated did not display toxicity even at high concentrations. Encouraged by their lack of toxicity, the test compounds were evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis and for their antifungal activity against C. neoformans and C. albicans. Some of the synthesized derivatives exhibited good and selective activity against M. smegmatis. Future studies will involve evaluation of synthesized candidate compounds as antitubercular, antiviral, antimalarial, and anti-inflammatory agents.
4- (4-Aminophenoxy)-N-methylpicolinamide (CAS: 284462-37-9) can be used in the preparation of Sorafenib (CAS: 284461-73-0). Sorafenib, an oral multikinase inhibitor, is classified as a bi-aryl urea. It acts on cell surface tyrosine kinase receptors and subsequent intracellular kinases involved in tumor cell proliferation and angiogenesis.
Application In Synthesis of [ 284462-37-9 ]
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
[0137] A solution of 4-aminophenol (256 mg, 2.35 mmol) in dry N,Ndimethylformamide (40 mL) was treated with potassium tert-butoxide (274 mg, 2.44 mmol), and the reddish-brown mixture was stirred at room temperature for 1 hour. The contents were treated with 3a and 3b (400 mg, 2.35 mmol) and potassium carbonate (974 mg, 7.05 mmol) and then heated to 80 C under argon for 4 h. The mixture was cooled to room temperature and poured into ethyl acetate (100 mL) and brine (400 mL). The combined organics were washed with brine, dried over sodium sulfate, and concentrated. The crude reaction mixture was purified by column chromatography (dichloromethane/methanol) to afford the desired 4-(4-aminophenoxy)-N- methylpyridine-2-carboxamide 4a (400 mg, 1 .65 mmol, 70%) and 4-(4- aminophenoxy)-N,N-dimethylpyridine-2-carboxamide (69%) 4b after column as a light-brown solid.
N-methyl-4-(4-((4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)phenoxy)picolinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56.1%
With toluene-4-sulfonic acid; In 1,4-dioxane; at 80℃; for 12h;
General procedure: To a solution of key intermediates 14a-b, 14c-d and 14e in 1,4-dioxane was added 4-substituted-2-chloro-pyrimidine and p-toluene sulfonic acid, and heated to 80 C for 12 h. The reaction was monitored by TLC until completed. The solution was evaporated to afford a crude product, which was purified by column chromatography (CH2Cl2/CH3OH, 100:1) on silica gel to afford the target compounds 17-19, 20-27, 28-36 and 37-40.
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