Structure of 89415-43-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Synthesis and Evaluation of Quinolino-Benzoxaboroles as Potential Antimicrobial Agents
Greeshma P. Kumpati ; Michael J. Williams ; Srinidhi Mereddy ; Joseph L. Johnson ; Shirisha Jonnalagadda ;
Abstract: Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on their relative non-toxicity, these compounds were further evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis. The synthesized compounds were also evaluated for antifungal activity in C. albicans and C. neoformans.
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Keywords: Benzoxaboroles ; Aminobenzoxaboroles ; Quinolino-Benzoxaboroles ; Anti-Microbial Agents
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Synthesis and Exploration of Quinolino-Benzoxaboroles as Potential Therapeutic Agents
Kumpati, Greeshma P ;
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.
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Purchased from AmBeed: 391-82-2 ; 611-35-8 ; 61964-08-7 ; 86-98-6 ; 284462-37-9 ; 89415-43-0
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CAS No. : | 89415-43-0 |
Formula : | C6H8BNO2 |
M.W : | 136.94 |
SMILES Code : | NC1=CC=C(B(O)O)C=C1 |
MDL No. : | MFCD01074656 |
InChI Key : | MKPDAJWEBQRQCO-UHFFFAOYSA-N |
Pubchem ID : | 2734615 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 1 ,3-thiazole-4-carboxylic acid (2.5 g) was added dry DMF (68 ml_), DIPEA (6.67 ml.) and HATU (13.1 g). The reaction was stirred at room temperature for 1 h under nitrogen. (4- Aminophenyl)boronic acid (5.1 g) was added and the reaction was stirred for 24 h, then partitioned between EtOAc and saturated sodium bicarbonate solution. The organic phases were washed further with saturated sodium bicarbonate solution, water, 2N HCI (x 2) and brine. The organic phases were passed through a hydrophobic frit and evaporated in vacuo. The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 0-100% EtOAc in cyclohexane to give the title compound. MS calcd for (Ci0H9BN2O3S + H)+: 331 MS found (electrospray): (M+H)+ = 331 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 85℃; for 10h; | To a solution of Example 223A (3.1 g, 13 mmol) in dimethoxyethane (25 mL) was added (4-aminophenyl)boronic acid (2.77 g, 16 mmol) and Na2CO3 (3.38 g, 31.2 mmol) in water (6 mL) followed by 1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride:dichloromethane:complex (652 mg, 0.8 mmol). The mixture was heated to 85° C. for 10 hours. After cooling to room temperature, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water followed by brine then dried over magnesium sulfate. After filtration and concentration, the crude product was purified by flash chromatography (1percent-100percent ethyl acetate/hexane) to provide the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium sulfate; In dichloromethane; at 20℃; | The preparation method of <strong>[4773-96-0]mangiferin</strong> cholic acid derivative includes the following steps:(1) Mangiferin and p-aminophenylboronic acid are fed in 1: 1 equivalent amounts, using anhydrous magnesium sulfate as a catalyst, and reacting in an anhydrous organic solvent, and stirring and reacting at room temperature. The reaction process is detected by thin-layer chromatography; After the filtration, freeze-dry and recrystallize with DMSO to obtain the primary product; |
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