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Synthesis and structure-activity relationship of 7-(substituted)-aminomethyl-4-quinolone-3-carboxylic acid derivatives

Gram-positive organisms have re-emerged as the major hospital pathogens, which make the unmet medical needs for antibacterial therapy even worse. In searching for potent agents against Gram-positive pathogens, novel 7-(substituted)-aminomethyl-quinolone-3-carboxylic acids were designed, synthesized, and evaluated for their antibacterial activities in vitro. Many 7-monoarylaminomethyl derivatives exhibited high potency against Gram-positive organisms compared to reference agents: vancomycin and pazufloxacin. Additionally, a few 7-monoalkylaminomethyl derivatives exhibited good activities against both Gram-positive and Gram-negative organisms.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The relative toxicity of compounds in mainstream cigarette smoke condensate

Many different in vivo and in vitro tests are currently used to assess the toxicity of chemicals and complex mixtures such as cigarette smoke condensate. In vivo tests include assays in rodents to determine carcinogenicity, tumorigenicity and reproductive effects. In vitro tests of mutagenicity are conducted with both bacterial and mammalian cell systems. A first step towards lowering the toxicity of cigarette smoke condensate is the identification of the relevant compounds. However, changing the concentration of a given smoke component may not linearly alter the biological activity of the complex mixture due to interactive effects. The ‘effective toxicity’ of a chemical constituent is a function of the concentration, the metabolic fate, the potency in in vivo and in vitro assays, and the ability to reach the target tissues. The logarithm of the octanol-water partition coefficient (log P) is an important parameter since it affects metabolism, biological transport properties and intrinsic toxicity. Using concentration data from the International Agency for Cancer Research (IARC), biological activity data from the Registry of Toxic Effects of Chemical Substances (RTECS) database and measured and calculated log P values, we have rank ordered some of the important compounds in cigarette smoke condensate by their measured or potential toxicity. Condensates from different cigarette brands, tar categories and styles vary in their concentrations of these compounds. Chemicals of greater commercial or scientific interest may be toxicity tested more extensively, thereby increasing the probability of positive test results and highlighting the need for consideration of structure-activity relationships. Copyright (C) 2000 Elsevier Science Ltd.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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POTENTIOMETRIC STUDIES ON COMPLEXES OF SILVER(I) IN SOLUTIONS. PART V. RELATIONSHIP BETWEEN STABILITY CONSTANTS OF Ag(I) COMPLEXES OF PYRIDINE DERIVATIVES AND HAMMET’S ? COEFFICIENTS

By means of the potentiometric method, the processes of formation of Ag(I) complexes of 3-acetyl-, 3-hydroxymethyl-, 2-ethyl-, 2,4-dimethyl-, 2,4,6-trimethyl-, 2-amino-5-methyl-, and 2-amino-4-methylpyridines have been examined in aqueous solutions (I = 0.5 (KNO3), t = 25 deg C).Correlation has been found between pKa and stability coefficient Sf and substituent constants ? for 19 Ag(I) compounds with 3- and 4-substituted pyridine derivatives.Positive value of the slope of Sf = f(?) straight line dependence evidences that the contribution of ?M -> L bond in the metal-ligand co-ordination bond is considerable.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Cationic (fluoromesityl)palladium(II) complexes

Halide abstraction from [Pd(mu-Cl)(Fmes)(NCMe)]2 (Fmes = 2,4,6-tris(trifluoromethyl)phenyl or nonafluoromesityl) with TlBF4 in CH2Cl2/MeCN gives [Pd(Fmes)(NCMe)3]BF4, which reacts with monodentate ligands to give the monosubstituted products trans-[Pd(Fmes)L(NCMe)2]BF4 (L = PPh3, P(o-Tol)3, 3,5-lut, 2,4-lut, 2,6-lut; lut = dimethylpyridine), the disubstituted products trans-[Pd(Fmes)(NCMe)(PPh3)2]BF4, cis-[Pd(Fmes)(3,5-lut)2(NCMe)]BF4, or the trisubstituted products [Pd(Fmes)L3]BF4 (L = CNtBu, PHPh2, 3,5-lut, 2,4-lut). Similar reactions using bidentate chelating ligands give [Pd(Fmes)(L-L)(NCMe)]BF4 (L-L = bipy, tmeda, dppe, OPPhPy2-N,N?, (OH)(CH3)CPy2-N,N?). The complexes trans-[Pd(Fmes)L2(NCMe)]BF4 (L = PPh3, tht) (tht = tetrahydrothiophene) and [Pd(Fmes)(L-L)(NCMe)]BF4 (L-L = bipy, tmeda) were obtained by halide extraction with TlBF4 in CH2Cl2/MeCN from the corresponding neutral halogeno complexes trans-[Pd(Fmes)ClL2] or [Pd(Fmes)Cl(L-L)]. The aqua complex trans-[Pd(Fmes)(OH2)(tht)2]BF4 was isolated from the corresponding acetonitrile complex. Overall, the experimental results on these substitution reactions involving bulky ligands suggest that thermodynamic and kinetic steric effects can prevail affording products or intermediates different from those expected on purely electronic considerations. Thus,water, whether added on purpose or adventitious in the solvent, frequently replaces in part other better donor ligands, suggesting that the smaller congestion with water compensates for the smaller M-OH2 bond energy.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The UV difference spectra as a characteristic feature of phenols and aromatic amines

Measurements of the difference absorption spectra were made for 12 phenols and 11 aromatic amines. Aqueous solutions of the same concentration and pH values 8-13 and 1-2 were measured against each other. The difference spectra were found to have a similar run within the group of compounds: monohydroxyl phenols, naphthols, quinolines, aniline and its derivatives and pyridine and its derivatives. The spectra reflect the changes in the conjugated bond systems caused by shifts in acid-base equilibria of the compounds examined.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Metal- and base-free regioselective thiolation of the methyl C(sp3)-H bond in 2-picoline: N -oxides

A one-pot, two-step synthesis of pyridine-2-ylmethyl thioethers is developed through a TFAA-mediated [3,3]-sigmatropic rearrangement of pyridine N-oxides and TBAB-catalyzed direct conversion of trifluoroacetates into thioethers under metal- and base-free conditions. This methodology enables thiolation of the unactivated methyl C(sp3)-H bond in 2-picolines with thiols. Remarkable features of the method include high regioselectivity, step- and atom-economy, mild conditions, simple operation, wide substrate scope and scalability. Furthermore, the method has been successfully applied to the synthesis of omeprazole sulfide and rabeprazole sulfide without the need for TBAB catalysis. A comprehensive green chemistry metrics analysis indicated that this method is much more efficient and greener than the reported synthesis of rabeprazole sulfide.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Determination of acidity constants by the capillary electrophoresis internal standard method. IV. Polyprotic compounds

The IS-CE method is developed for pKa determination of polyprotic compounds. In this method, the internal standard (IS) and the polyprotic test compound are injected into the capillary electrophoresis (CE) system in buffers with appropriate pH. The pH of the buffers is not externally measured, but determined inside the capillary from the mobilities of the internal standards. Then the pKa values of the polyprotic compounds are obtained by fitting its mobilities to the in situ pH values. The method is faster than the classical CE method (a diprotic compound can be done in less than 15min), and also than other methods like potentiometric and spectrophotometric titrations. The method has been successfully applied to 20 polyprotic test compounds of different chemical nature, including compounds with extreme or very close pKa values.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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HUMAN PLASMA KALLIKREIN INHIBITORS

Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents

Several analogs of 2,3-diaryl pyrroles were synthesized and evaluated as inhibitors of Eimeria tenella cGMP-dependent protein kinase and in in vivo anticoccidial assays. A 4-fluorophenyl group enhances both in vitro and in vivo activities. The most potent analogs are the 5-(N-methyl, N-ethyl, and N-methylazetidine methyl) piperidyl derivatives 12, 23, and 34. These compounds have a broad spectrum of activity. Based on the in vivo efficacy and cost of synthesis, the N-ethyl analog 23 was chosen as a novel anticoccidial agent for a field trial.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A Practical Parallel Synthesis of 2-Substituted Indolizines

A practical parallel synthesis of 2-substituted indolizines 4 via phase-separation techniques is reported. Their further transformation into indolizidines 5 is also described.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis