Search results for "Amides"
showing 10 items of 552 documents
Tachykinin NK(2) receptors facilitate acetylcholine release from guinea-pig isolated trachea.
2000
The release of newly synthesised [3H]acetylcholine was evoked by electrical field stimulation (5 Hz, 600 pulses) of epithelium-deprived guinea-pig trachea strips after sensory neuropeptides depletion with 3 microM capsaicin. The selective tachykinin NK(2) receptor agonist [betaAla(8)]neurokinin A-(4-10) increased in a concentration-dependent manner the electrically-induced release of [3H]acetylcholine. The facilitatory effect was antagonised by the selective non-peptide tachykinin NK(2) receptor antagonist, SR 48968 (apparent pK(B) 8.9). The tachykinin NK(1) and NK(3) receptor agonists substance P methyl ester and senktide (both 10 and 100 nM), respectively, did not affect the evoked releas…
Unsaturated syn- and anti-1,2-Amino Alcohols by Cyclization of Allylic Bis-trichloroacetimidates. Stereoselectivity Dependence on Substrate Configura…
2014
Disubstituted allylic bis-imidates undergo Lewis acid catalyzed or spontaneous cyclization to oxazolines, which are precursors of unsaturated amino alcohols. Stereoselectivity of the cyclization is mainly determined by the substrate configuration. Highly selective cis-oxazoline formation is achieved starting from anti-E-bis-imidates while trans-oxazoline predominantly forms from anti-Z-bis-imidates. On the basis of DFT calculations, the stereoselectivity trends can be explained by the formation of the energetically most stable carbenium ion conformation, followed by the cyclization via most favorable bond rotations.
Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides
2012
Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…
Identification of a new series of amides as non-covalent proteasome inhibitors
2014
Proteasome inhibition has emerged as an important therapeutic strategy for the treatment of multiple myeloma (MM) and some forms of lymphoma, with potential application in other types of cancers. 20S proteasome consists of three different catalytic activities known as chymotrypsin-like (ChT-L), trypsin-like (T-L), and, post-glutamyl peptide hydrolyzing (PGPH) or caspase-like (C-L), which are located respectively on the β5, β2, and β1 subunits of each heptameric β rings. Currently a wide number of covalent proteasome inhibitors are reported in literature; however, the less widely investigated non-covalent inhibitors might be a promising alternative to employ in therapy, because of the lack o…
Optimisation of gradient elution with serially-coupled columns. Part I: single linear gradients.
2014
A mixture of compounds often cannot be resolved with a single chromatographic column, but the analysis can be successful using columns of different nature, serially combined through zero-dead volume junctions. In previous work (JCA 1281 (2013) 94), we developed an isocratic approach that optimised simultaneously the mobile phase composition, stationary phase nature and column length. In this work, we take the challenge of implementing optimal linear gradients for serial columns to decrease the analysis time for compounds covering a wide polarity range. For this purpose, five ACE columns of different selectivity (three C18 columns of different characteristics, a cyano and a phenyl column) we…
Cooperativity of H-bonding and anion–π interaction in the binding of anions with neutral π-acceptors
2012
A rare anion-π complex between bromide and a neutral receptor is reported and related receptor systems are studied with a series of anions. The interaction is observed in the solid state and in solution, and further evidence for it is obtained by a computational study.
New anionic cobalt complexes using highly hindered bis-amides with varying donor abilities as ligands.
2007
Four potential tetradentate ligands of formulae 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)ethane (H(4)L(1), 1), 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)propane (H(4)L(2), 2), 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)benzene (H(4)L(3), 3) and 1,8-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)naphthalene (H(4)L(4), 4) have been prepared and the crystal structures of three of them (1, 3 and 4) determined by single crystal X-ray diffraction. The investigation of their complexing ability toward Co(II) afforded the compounds of formulae [Co(III)(L(3))Na(I)(H(2)O)(2)] (5), [Co(III)(L(n))Li(I)(H(2)O)2] with n = 1 (6), 2 (7) and 3 (8) and [Co(II)(L(4))Li(I)(2)] (9). Complexes 5-8 are squa…
A bis(triazole)benzamide receptor for the complexation of halide anions and neutral carboxylic acid guests. Guest-controlled topicity and self-assemb…
2012
Bis(triazole)benzamide 1 has been readily synthesized by means of Cu-catalyzed 1,3-dipolar cycloaddition and its ability to bind halide anions and neutral gallic acid derivative 12GA has been theoretically and experimentally investigated. The cavity defined by the N-H amide group and the vicinal aromatic hydrogens is suitable to form H-bonding arrays with halide guests. The stability of complexes 1·Cl- and 1·Br- is very similar, as DFT calculations predict and 1H NMR titration experiments confirm. The zigzag "anti" conformation of the molecule generates two regions with complementary positive and negative potentials that favor the statistical complexation of two molecules of the neutral car…
Synthesis and antifungal activity of new N-(1-phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides
2002
N-(1-Phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides 6, with a Benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 5 with potassium iodide for 1 h in order to study the role on the antifungal activity of the N-substitution with an aromatic heterocyclic system on benzamide moiety. Among the tested iododerivatives, compounds 6d,f,g,h possess interesting activities toward some phytopathogenic fungal strains.
Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice
2013
The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice recei…