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Imidazole

About: Imidazole is a research topic. Over the lifetime, 10097 publications have been published within this topic receiving 143499 citations. The topic is also known as: Him & IMD.


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Journal ArticleDOI
01 Mar 1978-Nature
TL;DR: The three-dimensional structure of plastocyanin, a blue or "Type 1" copper-protein, has been determined at a resolution of 2.7 A as discussed by the authors, and it is coordinated by a cysteine thiol group, a methionine thioether group and two histidine imidazole groups.
Abstract: The three-dimensional structure of plastocyanin, a ‘blue’ or ‘Type 1’ copper-protein, has been determined at a resolution of 2.7 A. The copper atom has a highly distorted tetrahedral coordination geometry. It is coordinated by a cysteine thiol group, a methionine thioether group, and two histidine imidazole groups.

666 citations

Journal ArticleDOI
TL;DR: TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels, suggesting that TRAM- 34 and related compounds may hold therapeutic promise as immunosuppressants.
Abstract: The antimycotic clotrimazole, a potent inhibitor of the intermediate-conductance calcium-activated K(+) channel, IKCa1, is in clinical trials for the treatment of sickle cell disease and diarrhea and is effective in ameliorating the symptoms of rheumatoid arthritis. However, inhibition of cytochrome P450 enzymes by clotrimazole limits its therapeutic value. We have used a rational design strategy to develop a clotrimazole analog that selectively inhibits IKCa1 without blocking cytochrome P450 enzymes. A screen of 83 triarylmethanes revealed the pharmacophore for channel block to be different from that required for cytochrome P450 inhibition. The "IKCa1-pharmacophore" consists of a (2-halogenophenyl)diphenylmethane moiety substituted by an unsubstituted polar pi-electron-rich heterocycle (pyrazole or tetrazole) or a -CN group, whereas cytochrome P450 inhibition absolutely requires the imidazole ring. A series of pyrazoles, acetonitriles, and tetrazoles were synthesized and found to selectively block IKCa1. TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels. Using TRAM-34, we show that blocking IKCa1 in human lymphocytes, in the absence of P450-inhibition, results in suppression of mitogen-stimulated [(3)H]thymidine incorporation of preactivated lymphocytes with EC(50)-values of 100 nM-1 microM depending on the donor. Combinations of TRAM-34 and cyclosporin A are more effective in suppressing lymphocyte mitogenesis than either compound alone. Our studies suggest that TRAM-34 and related compounds may hold therapeutic promise as immunosuppressants.

600 citations

Journal ArticleDOI
Klaus-Dieter Kreuer1, Annette Fuchs1, M. Ise1, M. Spaeth1, Joachim Maier1 
TL;DR: The properties of imidazole (pyrazole) as a solvent for acidic protons in polymers and liquids are reported in this article, where the creation of protonic defects and the mobility of protons are found to be similar to the situation in corresponding water containing systems.

557 citations

Journal ArticleDOI
TL;DR: Evidence is presented that the reverse protonation of imidazol-2-yl carbenes by solvent water is limited by solvent reorganization and occurs with a rate constant of kHOH = kreorg = 10(11) s-1, and a simple rationale for the observed substituent effects on the thermodynamic stability of N-heterocyclicCarbenes is presented.
Abstract: We report second-order rate constants kDO (M-1 s-1) for exchange for deuterium of the C(2)-proton of a series of simple imidazolium cations to give the corresponding singlet imidazol-2-yl carbenes in D2O at 25 degrees C and I = 1.0 (KCl). Evidence is presented that the reverse protonation of imidazol-2-yl carbenes by solvent water is limited by solvent reorganization and occurs with a rate constant of kHOH = kreorg = 10(11) s-1. The data were used to calculate reliable carbon acid pK(a)s for ionization of imidazolium cations at C(2) to give the corresponding singlet imidazol-2-yl carbenes in water: pKa = 23.8 for the imidazolium cation, pKa = 23.0 for the 1,3-dimethylimidazolium cation, pKa = 21.6 for the 1,3-dimethylbenzimidazolium cation, and pKa = 21.2 for the 1,3-bis-((S)-1-phenylethyl)benzimidazolium cation. The data also provide the thermodynamic driving force for a 1,2-hydrogen shift at a singlet carbene: K12 = 5 x 10(16) for rearrangement of the parent imidazol-2-yl carbene to give neutral imidazole in water at 298 K, which corresponds to a favorable Gibbs free energy change of 23 kcal/mol. We present a simple rationale for the observed substituent effects on the thermodynamic stability of N-heterocyclic carbenes relative to a variety of neutral and cationic derivatives that emphasizes the importance of the choice of reference reaction when assessing the stability of N-heterocyclic carbenes.

464 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023490
2022889
2021189
2020228
2019266
2018289