- Polynuclear Ag(I)-N-heterocyclic carbene complexes: synthesis, electrochemical and in vitro anticancer study against human breast cancer and colon cancer
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Four new bis-imidazolium salts 3–6 and their di- and polynuclear silver(I)–N-heterocyclic carbene (Ag(I)–NHC) complexes 7–10 were synthesized and characterized by using various analytical techniques. Single-crystal studies of 8 revealed a dinuclear struct
- Habib, Aqsa,Iqbal, Muhammad Adnan,Bhatti, Haq Nawaz
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- Synthesis and biological evaluation of 1‐(Diarylmethyl)‐1h‐1,2,4‐triazoles and 1‐(diarylmethyl)‐1h‐imidazoles as a novel class of anti‐mitotic agent for activity in breast cancer
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We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)‐positive MCF‐7 breast cancer cells identified 5‐((2H‐1,2,3‐triazol‐1‐yl)(3,4,5‐trimethoxyphenyl)methyl)‐2‐methoxyphenol 24 as a potent antiproliferative compound with an IC50 value of 52 nM in MCF‐7 breast cancer cells (ER+/PR+) and 74 nM in triple‐negative MDA‐MB‐231 breast cancer cells. The compounds demonstrated significant G2/M phase cell cycle arrest and induction of apoptosis in the MCF‐7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF‐10A breast cells. The immunofluorescence staining of MCF‐7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds 19e, 21l, and 24 in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds 19e and 21l were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule‐disrupting agents for breast cancer.
- Ana, Gloria,Kelly, Patrick M.,Malebari, Azizah M.,Noorani, Sara,Nathwani, Seema M.,Twamley, Brendan,Fayne, Darren,O’boyle, Niamh M.,Zisterer, Daniela M.,Pimentel, Elisangela Flavia,Endringer, Denise Coutinho,Meegan, Mary J.
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- Stable group 8 metal porphyrin mono- And bis(dialkylcarbene) complexes: Synthesis, characterization, and catalytic activity
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Alkyl-substituted carbene (CHR or CR2, R = alkyl) complexes have been extensively studied for alkylcarbene (CHR) ligands coordinated with high-valent early transition metal ions (a.k.a. Schrock carbenes or alkylidenes), yet dialkylcarbene (CR2) complexes remain less developed with bis(dialkylcarbene) species being little (if at all) explored. Herein, several group 8 metal porphyrin dialkylcarbene complexes, including Fe- and Ru-mono(dialkylcarbene) complexes [M(Por)(Ad)] (1a,b, M = Fe, Por = porphyrinato dianion, Ad = 2-adamantylidene; 2a,b, M = Ru) and Os-bis(dialkylcarbene) complexes [Os(Por)(Ad)2] (3a-c), are synthesized and crystallographically characterized. Detailed investigations into their electronic structures reveal that these complexes are formally low-valent M(ii)-carbene in nature. These complexes display remarkable thermal stability and chemical inertness, which are rationalized by a synergistic effect of strong metal-carbene covalency, hyperconjugation, and a rigid diamondoid carbene skeleton. Various spectroscopic techniques and DFT calculations suggest that the dialkylcarbene Ad ligand is unique compared to other common carbene ligands as it acts as both a potent σ-donor and π-acceptor; its unique electronic and structural features, together with the steric effect of the porphyrin macrocycle, make its Fe porphyrin complex 1a an active and robust catalyst for intermolecular diarylcarbene transfer reactions including cyclopropanation (up to 90% yield) and X-H (X = S, N, O, C) insertion (up to 99% yield) reactions.
- Che, Chi-Ming,Huang, Jie-Sheng,Low, Kam-Hung,Wan, Qingyun,Wang, Hai-Xu,Zhang, Jun-Long,Zhou, Cong-Ying
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p. 2243 - 2259
(2020/03/11)
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- Design, synthesis and antifungal activity of some new imidazole and triazole derivatives
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Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral (1H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole. A novel series of azole derivatives was designed and synthesized as inhibitors of cytochrome P450 14α-demethylase and the compounds were investigated for antifungal activity. Copyright
- Rezaei, Zahra,Khabnadideh, Soghra,Zomorodian, Kamiar,Pakshir, Kyvan,Kashi, Giti,Sanagoei, Narges,Gholami, Sanaz
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experimental part
p. 658 - 665
(2012/06/29)
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- Synthesis, antibacterial and antifungal activities of bifonazole derivatives
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Two series of chlorinated benzhydryl imidazole and triazole derivatives were synthesized and tested in vitro against representative strains of potent pathogenic bacteria (Staphylococcus aureus CIP 4.83, Escherichia hirae CIP 5855, Pseudomonas aeruginosa CIP 82118, Escherichia coli CIP 53126) and fungi (Aspergillus niger IP 1431.83, Candida albicans IP 48.72, Candida krusei IP 208.52, Trichophython rubrum IP 1657.86). Most of these compounds were devoid of any antimicrobial activity, but several of them inhibited T. rubrum with MIC values in the range of 0.125 to 32 μg/mL, similar or superior to those of bifonazole and clotrimazole, used as standard controls. The replacement of the imidazole ring with a triazole moiety in these compounds led to derivatives with less antifungal activity. A preliminary SAR was undertaken on the effect of the number and the position of chlorine atoms on the distribution of negative charge on the surface of some compounds on antifungal activity. Copyright
- El Hage, Salome,Lajoie, Barbora,Feuillolay, Catherine,Roques, Christine,Baziard, Genevieve
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experimental part
p. 402 - 410
(2012/01/11)
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- Synthesis and structure-activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors
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A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole 1. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 μM), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen.
- Doiron, Jeremie,Soultan, Al Haliffa,Richard, Ryan,Toure, Mamadou Mansour,Picot, Nadia,Richard, Remi,Cuperlovic-Culf, Miroslava,Robichaud, Gilles A.,Touaibia, Mohamed
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experimental part
p. 4010 - 4024
(2011/10/30)
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- LuxR dependent quorum sensing inhibition by N,N′-disubstituted imidazolium salts
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Thirty N,N′-disubstituted imidazolium salts have been synthesized and evaluated as LuxR antagonists. Substitution on one of the imidazolium nitrogen atoms includes benzhydryl, fluorenyl or cyclopentyl substituent, and alkyl chains of various lengths on th
- Sabbah, Mohamad,Soulre, Laurent,Reverchon, Sylvie,Queneau, Yves,Doutheau, Alain
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scheme or table
p. 4868 - 4875
(2011/09/21)
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- The reaction of carbonyldiimidazole with alcohols to form carbamates and N-alkylimidazoles
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The reactions of non-benzylic primary and secondary aliphatic alcohols with carbonyldiimidazole (CDI) afford the corresponding carbamates but not N-alkylimidazoles. For benzylic primary alcohols, formation of N-alkylimidazoles proceeds reasonably at 170 °C in several different solvents and occurs by way of the initially formed carbamate. However, under these rather forcing conditions, or even at lower reaction temperatures, elimination is a significant side reaction for benzylic secondary alcohols with β-hydrogen atoms. With one exception, reactions of six N,N-disubstituted β-aminoalcohols with CDI to form N-alkylimidazoles proceed under relatively mild conditions and may occur by way of an aziridinium intermediate.
- Tang, Yuanqing,Dong, Yuxiang,Vennerstrom, Jonathan L.
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p. 2540 - 2544
(2007/10/03)
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- Optically active iridium imidazol-2-ylidene-oxazoline complexes: Preparation and use in asymmetric hydrogenation of arylalkenes
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This work explores the potential of iridium complexes of the N-heterocyclic carbene oxazoline ligands 1 in asymmetric hydrogenations of arylalkenes. The accessible carbene precursors, imidazolium salts 2, and robust iridium complexes 5 facilitated a disco
- Perry, Marc C.,Cui, Xiuhua,Powell, Mark T.,Hou, Duen-Ren,Reibenspies, Joseph H.,Burgess, Kevin
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p. 113 - 123
(2007/10/03)
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- Open-chain dications and betaines with imidazolium molecular motifs: Synthesis and structural aspects
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The synthesis of trinuclear open-chain prototypes gave variable yields: > 53% for dications 1·2X and 2·2X and > 80% for proton-ionizable dications 3·2X-5·2X incorporating 1H-1,2,4-triazole moieties. Deprotonation of the latter compounds resulted in the formation of the betaine counterparts 13·X-15·X. The courses of the dequaternization reactions of compounds 4·2X and 5·2X were also studied. The structural properties of dicationic protophanes 1·2X and 2·2X, containing bis(imidazolium) motifs, were examined by 1H and 13C NMR spectroscopy, electrospray mass spectrometry and by single-crystal X-ray diffraction analysis of the dication 1b·2PF6. Weak noncovalent interactions between the dications and the hexafluorophosphate ions bias the protophane conformation both in solution and in the solid state. X-ray diffraction reveals that the PF6- counterions are located in a channel formed by the dications (1b2+). Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Alcalde, Ermitas,Mesquida, Neus,Alemany, Montserrat,Alvarez-Rua, Carmen,Garcia-Granda, Santiago,Pacheco, Pedro,Perez-Garcia, Lluisa
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p. 1221 - 1231
(2007/10/03)
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- High-yield synthesis of novel imidazoles and triazoles from alcohols and phenols
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A variety of alcohols and phenols are converted into their corresponding imidazoles and triazoles in high yields by a facile reaction with N,N1-carbonyldiimidazole (CDI) or N,N1-carbonylditriazole (CDT) in acetonitrile. The reactions of allylic alcohols, enols and phenols with CDI or CDT are unprecedented. Evidence is provided which suggests that the reaction with alcohols proceeds via the corresponding carbamates by an S(N)i mechanism.
- Njar
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p. 2019 - 2028
(2007/10/03)
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- Chiral azole derivatives. 2. Synthesis of enantiomerically pure 1-alkylimidazoles
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4,5-Dicyanoimidazole has been reacted with racemic and enantiopure alcohols 7 (entries 1-7) under Mitsunobu conditions to give 1-alkyl-4,5-dicyanoimidazole derivatives 8, which in turn have been transformed by hydrolysis and decarboxylation into 1-alkylimidazoles 10 in good overall yield and high enantiomeric excess. In contrast, when applied to benzyl and benzhydryl alcohols (entries 8-15), this sequence afforded the final compounds in good overall yield, but as racemic mixtures. The 1-(1-phenylalkyl)imidazole derivative (S)-(+)-24 was, however, prepared in enantiopure form starting from the corresponding (S)-(-)-α-methylbenzylamine (21) using the Marckwald procedure, which entailed the alkylation of 21 with bromoacetaldehyde dimethyl acetal, followed by the construction of the imidazole ring through reaction with potassium thiocyanate and final Ra-Ni desulfuration. Following the same procedure, (S)-(+)-10c was also synthesized, proving the stereochemical outcome of the Mitsunobu reaction.
- Corelli,Summa,Brogi,Monteagudo,Botta
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p. 2008 - 2015
(2007/10/02)
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- Estrogen Synthetase Inhibitors. 2. Comparison of the in Vitro Aromatase Inhibitory Activity for a Variety of Nitrogen Heterocycles Substituted with Diarylmethane or Diarylmethanol Groups
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The preparation and in vitro aromatase inhibitory activity of a wide variety of heterocyclic (4,4'-dichlorodiphenyl)methanes and -methanols are described.The choice of the two diaryl-bearing moieties as a vehicle for the evaluation of the heterocycles was made by the comparison of series of imidazole and pyridine-derived compunds with similar pyrimidine compounds reported previously.A structural model for the most active compounds is also presented.The activity of a related series of compounds which contain two heterocyclic moieties was found to be consistent with the model.Many of the compounds evaluated, including representatives of the pyridine, imidazole, pyrimidine, pyrazole, triazole, thiazole, and isothiazole classes, exhibit EC50 potencies for aromatase inhibition at low nanomolar levels.These compunds are at least as potent as other nonsteroidal aromatase inhibitors reported previously.
- Jones, C. David,Winter, Mark A.,Hirsch, Kenneth S.,Stamm, Nancy,Taylor, Harold M.,et al.
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p. 416 - 429
(2007/10/02)
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- SYNTHESIS BY PHASE TRANSFER CATALYSIS OF N-BENZYL, N-DIPHENYLMETHYL AND N-TRIPHENYLMETHYL AZOLES AND BENZAZOLES: PROTON NMR AND CHROMATOGRAPHIC DATA AS A TOOL FOR IDENTIFICATION
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Pyrazole, imidazole, 1,2,4-triazole, indazole and benzotriazole were alkylated under phase transfer catalysis (PTC) with benzyl-, diphenylmethyl- and trityl chloride.Alkylation occured only at the ring nitrogen atoms of the heterocycle, except for indazole in which substitution took also place at position 3.A systematic study of the N- and C-substituted derivatives by proton NMR and chromatographic techniques has been done.
- Claramunt, Rosa M.,Elguero, Jose,Garceran, Rafael
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p. 2895 - 2906
(2007/10/02)
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