- Synthesis and electrochemical evaluation of 2-substituted imidazolium salts
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Herein, we report the synthesis, electrochemical, and computational evaluation of six 2-substituted imidazolium bromides and six 2-substituted imidazolium triflates. All final compounds were obtained in 2 or fewer synthetic steps from inexpensive starting
- Hogan, David T.,Sutherland, Todd C.
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- Mechanochemical and conformational study of N-heterocyclic carbonyl-oxime transformations
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New mechanochemical pathways for the transformation of six N-heterocyclic carbonyl compounds into oximes using hydroxylamine hydrochloride were explored. Reactions were performed first without any base since the heterocyclic moieties (imidazole, benzimidazole, pyridine and quinuclidine) have an intrinsic basic nitrogen atom. This green, solvent free method was suitable for all compounds (up to quantitative yields) except for N-benzyl substituted imidazole and benzimidazole-2-carbaldehyde. For the slower reacting aldehydes, reactions with liquid assisted grinding and addition of sodium hydroxide were performed as well. Conformational analysis and quantum-chemical calculations revealed steric and electronic reasons for the lower reactivity of N-benzyl substituted derivatives.
- Primoi, Ines,Hrenar, Tomica,Baumann, Kreimir,Krito, Lucija,Krii, Ivana,Tomi, Srdlanka
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p. 153 - 160
(2015/02/19)
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- Synthesis and antimicrobial profile of N-substituted imidazolium oximes and their monoquaternary salts against multidrug resistant bacteria
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Two different series of N-substituted imidazolium oximes and their monoquaternary salts were synthesized and biologically tested with respect to their ability to inhibit growth a diverse panel of antibiotic susceptible Gram-positive and antibiotic resistant Gram-negative bacteria as well fungal strains. The newly synthesized compounds were analyzed by spectral studies to confirm their structure. The preliminary results showed that all compounds tested possess promising antimicrobial potential against both susceptible Gram-positive and antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC values from 0.14 to 100.0 μg/mL. The structure-activity relationship demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary salts 6 and 7 attached directly to the imidazolium ring could be essential for observed remarkable inhibitory profiles against clinically important pathogens Pseudomonas aeruginosa (MIC = 0.14 μg/mL) and Klebsiella pneumoniae (MIC = 1.56 μg/mL). Furthermore, the broth microdilution assay was then used to investigate the antiresistance efficacy of compound 7 against fourteen extended-spectrum β-lactamase (ESBL)-producing strains in comparison to eight clinically relevant antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging between 0.39 and 12.50 μg/mL against all of ESBL-producing strains, which leads to the suggestion that may be interesting candidate for development of new antimicrobials to combat multidrug resistant Gram-negative bacteria.
- Od?ak, Renata,Sko?ibu?i?, Mirjana,Maravi?, Ana
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p. 7499 - 7506
(2013/11/19)
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- Selection of chiral zinc catalysts for the kinetic resolution of esters via dynamic templating
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Dynamic combinatorial libraries of chiral tetradentate bis-imine zinc(II) complexes have been prepared and screened for (1) their discrimination of enantiomeric picolinate esters and pyridyl phosphonate transition state analogs (TSAs) and (2) their cataly
- Kannappan,Nicholas
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supporting information
p. 90 - 100
(2013/04/10)
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- Novel Quinoline-Hepcidine Antagonists
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The present invention relates to novel hepcidin antagonists of the general formula (I), pharmaceutical compositions comprising them and the use thereof as medicaments, in particular for treatment of disorders in iron metabolism, such as, in particular, iron deficiency diseases and anaemias, in particular anaemias in connection with chronic inflammatory diseases (ACD: anaemia of chronic disease and AI: anaemia of inflammation).
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- Syntheses, protonation constants and antimicrobial activity of 2-substituted N-alkylimidazole derivatives
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A series of N-alkylimidazole-2-carboxylic acid, N-alkylimidazole-2- carboxaldehyde and N-alkylimidazole-2-methanol derivatives [alkyl = benzyl, methyl, ethyl, propyl, butyl, heptyl, octyl and decyl] have been synthesized and the protonation constants determined. The antimicrobial properties of the compounds were tested against Gram-negative (Escherichi coli), Gram-positive (Staphylococcus aureus & Bacillus subtilis subsp. spizizenii) bacterial strains and yeast (C. albicans). Both the disk diffusion and broth microdilution methods for testing the antimicrobial activity showed that N-alkylation of imidazole with longer alkyl chains and the substitution with low pKa group at 2-position resulted in enhanced antimicrobial activity. Particularly, the N-alkylimidazole-2-carboxylic acids exhibited the best antimicrobial activity due to the low pKa of the carboxylic acid moiety. Generally, all the N-alkylimidazole derivatives were most active against the Gram-positive bacteria [S. aureus (MIC = 5-160 μg mL-1) and B. subtilis subsp. spizizenii (5-20 μg mL-1)], with the latter more susceptible. All the compounds showed poor antimicrobial activity against both Gram-negative (E. coli, MIC = 0.15 to >2500 μg mL-1) bacteria and all the compounds were inactive against the yeast (Candida albicans).
- Kleyi, Phumelele,Walmsley, Ryan S.,Gundhla, Isaac Z.,Walmsley, Tara A.,Jauka, Tembisa I.,Dames, Joanna,Walker, Roderick B.,Torto, Nelson,Tshentu, Zenixole R.
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p. 231 - 238
(2013/01/15)
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- Synthesis and biological evaluation of novel 2-(2-arylmethylene)hydrazinyl- 4-aminoquinazoline derivatives as potent antitumor agents
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Two series of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives were synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. Most compounds displayed moderate to excellent activity, with IC50 values ranging from 0.015 to 4.09 μM against all tested cell lines, respectively. The most promising compound 9p (E)-2-(2-((1-(2,3-dichlorobenzyl)-1H-imidazol-2-yl)methylene) hydrazinyl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine with IC50 values of 0.031 μM, 0.015 μM, 0.53 μM and 0.58 μM, which was 4- to 224 times more active than references 10 and Iressa, had emerged as a lead for further structural modifications.
- Jiang, Nan,Zhai, Xin,Zhao, Yanfang,Liu, Yajing,Qi, Baohui,Tao, Haiyan,Gong, Ping
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p. 534 - 541
(2012/09/07)
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- Asymmetric Copper(II)-catalysed nitroaldol (Henry) reactions utilizing a chiral C1-symmetric dinitrogen ligand
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A series of stable chiral C1-symmetric dinitrogen ligands were conveniently synthesized in high yields by condensation of chiral amines [(-)-exo-bornylamine or (+)-(1S,2S,5R)-menthylamine] with various substituted imidazolecarbaldehydes. With the assistance of base, the ligand L1 in combination with CuCl2·2H2O (2.5 mol-% or 5.0 mol-%) can efficiently promote nitroaldol (Henry) reactions between a variety of aldehydes and nitromethane. Both aromatic and aliphatic aldehydes were tolerated in our catalytic system, affording the expected nitroalcohol products in high yields (up to 97%) and with good enantioselectivities (up to 96%) under mild reaction conditions. A series of chiral C1-symmetric dinitrogen ligands were conveniently synthesized in high yields by condensations of chiralamines with various substituted imidazolecarbaldehydes. The ligand L1 in conjunction with CuCl2·2H2O can efficiently promote nitroaldol (Henry) reactions between various aldehydes and nitromethane in high yields (up to 97%) and with good enantioselectivities (up to 96%).
- Zhou, Yirong,Gong, Yuefa
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p. 6092 - 6099
(2011/11/29)
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- METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)
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Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.
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Page/Page column 200-201
(2011/11/01)
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- DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
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A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
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Page/Page column 101
(2010/03/02)
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- MUSCARINIC RECEPTOR ANTAGONISTS
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The present invention generally relates to muscarinic receptor antagonists of formula I, which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors. Formula (I) wherein Het: is heterocyclyl or heteroaryl X: O, S or NR1 and the other substituents are defined as in the claims.
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Page/Page column 8
(2010/06/19)
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- 1-(Aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof
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Certain 1-(aromatic- or heteroaromatic-substituted-3-(heteroaromatic substituted)-1,3-propanediones are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
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- Substituted heterocyclylisoquinolinium salts and compositions and method of use thereof
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Substitutued heterocyclylisoquinolinium salts, pharmaceutical compositions containing them and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.
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- 5,10,15,20-Tetrakis(N-protected-imidazol-2-yl)porphyrins
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It is shown that examples of title porphyrins can be prepared from suitably N-protected imidazole-2-carboxaldehydes and pyrrole in refluxing propionic acid: subsequent deprotection, affords a synthetic route to 5,10,15,20-tetrakis(substituted-imadizol-2-y) porphyrins (TIPs).
- Milgrom, Lionel R.,Dempsey, Philip J.F.,Yahioglu, Gokhan
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p. 9877 - 9890
(2007/10/03)
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- Some Benzyl-Substituted Imidazoles, Triazoles, Tetrazoles, Pyridinethiones, and Structural Relatives as Multisubstrate Inhibitors of Dopamine β-Hydroxylase. 4. Structure-Activity Relationships at the Copper Binding Site
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Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine β-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor.Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously.The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity.An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitor potency.In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced.Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.
- Kruse, Lawrence I.,Kaiser, Carl,DeWolf, Walter E.,Finkelstein, Joseph A.,Frazee, James S.,et al.
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p. 781 - 789
(2007/10/02)
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- Annelation Reactions of N-Heterocycles to Condensed Pyridones with Bridgehead Nitrogen
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The Horner-Wittig reaction of aromatic and heteroaromatic aldehydes with phosphono succinates gives the methylenesuccinates 2a-m and 4a-k in satisfactory yields.The compounds obtained have the E-configuration, as shown by 1H-NMR-spectroscopic and by chemi
- Linke, Siegfried,Kurz, Juergen,Lipinski, Dietmar,Gau, Wolfgang
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p. 542 - 556
(2007/10/02)
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