thiourea and quinoline

We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure-activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds.

Topics: Anti-Bacterial Agents; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Quinolines; Structure-Activity Relationship; Thiourea; Vancomycin

A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model.

Topics: Animals; Dogs; Female; Hepatocytes; High-Throughput Screening Assays; Humans; I-kappa B Kinase; Macaca mulatta; Male; Mice; Protein Kinase Inhibitors; Quinolines; Rats; Semicarbazides; Structure-Activity Relationship; Thiourea

Generally, amine-catalyzed enantioselective transformations rely on chiral enamine or unsaturated iminium intermediates. Herein, we report a protocol involving dual activation by an aromatic iminium and hydrogen-bonding. An enantioselective aza-Michael-Henry domino reaction of 2-aminobenzaldehydes with nitroolefins has been developed through this protocol using primary amine thiourea catalysts to provide a variety of 3-nitro-1,2-dihydroquinolines in moderate yields and with up to 90% ee. The mechanism for the catalytic enantioselective reaction was confirmed by ESI mass spectrometric detection of the reaction intermediates. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules.

Topics: Amines; Benzaldehydes; Catalysis; Cyclization; Electrochemistry; Hydrogen; Ions; Molecular Structure; Quinolines; Stereoisomerism; Thiourea

In capillary electrochromatography with the mixed-mode stationary phase, while the transfer of solutes could be controlled by the contributions of chromatography (reversed-phase and ion exchange), the transfer of charged solutes could be influenced by electrophoresis transfer. According to the principle of ion independent transfer and several kinds of interaction between solute, mobile phase, and stationary phase, an theoretical expression was derived to describe the relationship among the apparent transfer velocity of solute, the transfer velocities in various forms and the diversified interactions. The studies focused on the influence of various parameters (e.g., pH, organic modifier content, stationary phase proportion) and the transfer characters of various solutes in the mixed-mode capillary electroosmotic chromatography (CEC). These results demonstrate that electroosmotic flow in the mixed stationary phase electrochromatography are kept high and steady within wide ranges of pH and organic modifier content. The separation was affected by the pH through the change of the solutes conformation. The influence of neutral solutes by organic modifier complies with the rule of conventional reversed-phase CEC. The separation of charged solutes was influenced evidently by the compete reagents which could improve the shape of the peak, but it was not so important as in the conventional ion exchange chromatography due to the adjustment by the function of electrophoresis.

Topics: Benzoic Acid; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; Chromatography, Micellar Electrokinetic Capillary; Electrons; Osmosis; Quinolines; Solutions; Thiourea

Topics: Biguanides; Hydroxyquinolines; Quinolines; Thiourea