- Novel phenethylimidazolium based ionic liquids: Design, microwave synthesis, in-silico, modeling and biological evaluation studies
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An eco-friendly preparation method for the novel bioactive imidazolium ionic liquids halides (ILs) was developed under microwave-assisted conditions. Synthesized ILs were characterized by spectroscopic techniques. Selected ILs were investigated for their antimicrobial activity against highly resistant Gram-positive and Gram-negative bacterial strains. Overall, 3-(2-chlorobenzyl)-1-phenethyl-1H-imidazol-3-iumchloride (4) showed high antimicrobial activity against the Staphylococcus aureus strain in the inhibition zone tests and displayed low MIC and MBC levels against almost all tested bacteria. Furthermore, the ILs were screened in vitro against human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and human colon carcinoma (Caco-2) cell lines. The screening results showed excellent to moderate anticancer activity across the ILs. Among the synthesized ILs, Overall, 3-(2-chlorobenzyl)-1-phenethyl-1H-imidazol-3-ium chloride (4) and 1-phenethyl-3-(3-phenoxypropyl)-1H-imidazol-3-ium bromide (7) were found to exhibit the most promising ant proliferative effects and had the lowest IC50 values. The docking study suggested strong interaction of ILs with DNA with binding energy ranging from ?4.9 to ?4.1 kcal/mol. ILs 4 and 7 were most strongly bonded with ?4.9 and ?4.8 kcal/mol binding energy; confirming in vitro anticancer results.
- Ali, Imran,Almutairi, Saud M.,Alqurashy, Bakheet A.,Alrefaei, Abdulwahed F.,Hammouti, Belkheir,Manoharadas, Salim,Messali, Mouslim,Sahu, Pramod K.,Titi, Abderrahim,Touzani, Rachid
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- HETEROARYL COMPOUNDS COMPRISING NITROGEN AND USE THEREOF
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The present invention relates to heteroaryl compounds comprising nitrogen and use thereof, and more specifically to compounds which exhibit a remarkable effect on inhibiting proliferation of cancer cells and metastasis and recurrence of cancer, a preparat
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Paragraph 0062; 0063; 0064; 0065; 0094'; 0095; 0096; 0097
(2017/11/14)
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- A PROCESS FOR THE PREPARATION OF ALCAFTADINE
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An improved process for preparation of Alcaftadine, its crystalline form or its pharmaceutically acceptable salts is disclosed alongwith a process for purification of Alcaftadine or its pharmaceutically acceptable salts.
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Page/Page column 17; 18
(2014/06/23)
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- Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors
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Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.
- R?hrig, Ute F.,Majjigapu, Somi Reddy,Chambon, Marc,Bron, Sylvian,Pilotte, Luc,Colau, Didier,Van Den Eynde, Beno?t J.,Turcatti, Gerardo,Vogel, Pierre,Zoete, Vincent,Michielin, Olivier
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p. 284 - 301
(2014/08/05)
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- Substituted heteroaromatic compounds: Effect on nicotine self-administration in rats
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Rationale: Certain compounds that nonselectively inhibit a prominent human nicotine-metabolizing enzyme (i.e., human cytochrome P-450 2A6, hCYP 2A6) showed inhibition of smoking in humans. However, a comprehensive examination of hCYP 2A6 inhibitors to dec
- Cashman, John R.,Okolotowicz, Karl,Cerny, Matt,Johnson, Robert,Janowsky, Aaron,Azar, Marc R.
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experimental part
p. 637 - 648
(2012/09/07)
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- Heme Oxygenase Inhibition by α-(1H-Imidazol-1-yl)-ω-phenylalkanes: Effect of Introduction of Heteroatoms in the Alkyl Linker
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Several α-(1H-imidazol-1-yl)-ω-phenylalkanes were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds were found to be potent and selective for the stress-induced isozyme HO-1, showing mostly weak activity toward the cons
- Vlahakis, Jason Z.,Lazar, Carmen,Roman, Gheorghe,Vukomanovic, Dragic,Nakatsu, Kanji,Szarek, Walter A.
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experimental part
p. 897 - 902
(2012/07/30)
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- HEME-OXYGENASE INHIBITORS AND USE OF THE SAME IN THE TREATMENT OF CANCER AND DISEASES OF THE CENTRAL NERVOUS SYSTEM
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Disclosed are compounds of the general formula (1): compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.
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Page/Page column 70
(2009/01/24)
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- Photochemical intramolecular aromatic substitutions of the imidazol-2-yl radical are superior to those mediated by Bu3SnH
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Six-membered photochemical cyclisations of 2-iodo-N-(2-arylethyl)imidazoles proceeded regioselectively in higher yields than the equivalent tin hydride-mediated reactions. The decrease in yield of cyclisation products, 5,6-dihydroimidazo[2,1-a]isoquinolines containing strongly deactivating substituents on the aryl ring confirmed the electrophilic nature of the σ-imidazol-2-yl radicals. The seven-membered cyclisation was only successful under photochemical conditions, as radical reduction occurred with tin hydride. Nitration of 5,6-dihydroimidazo[2,1-a]isoquinoline with nitric/sulfuric acid occurred at the 2- and 8-positions. The Royal Society of Chemistry 2006.
- Clyne, Mairead A.,Aldabbagh, Fawaz
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p. 268 - 277
(2007/10/03)
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- Synthesis of enantiopure 1-substituted, 1,2-disubstituted, and 1,4,5-trisubstituted imidazoles from 1,2-amino alcohols
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A highly versatile method for the preparation of enantiopure 1-substituted, 1,2-disubstituted, and 1,4,5-trisubstituted imidazoles was developed by using the cyclocondensation reaction of a 1,2-dicarbonyl compound, an aldehyde, a 1,2-amino alcohol, and ammonium acetate.
- Matsuoka, Yuki,Ishida, Yasuhiro,Sasaki, Daisuke,Saigo, Kazuhiko
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p. 8199 - 8206
(2007/10/03)
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- Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17α-hydroxylase/17,20-lyase (P45017α)
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We report the preliminary results of the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a number of phenyl alkyl imidazole-based compounds as inhibitors of the two components of 17α-hydroxylase/17,20-lyase (P45017α), that is, 17α-hydroxylase (17α-OHase) and 17,20-lyase (lyase). The results show that N-3-(4-bromophenyl) propyl imidazole (12) (IC50 = 2.95 μM against 17α-OHase and IC50 = 0.33 μM against lyase) is the most potent compound within the current study, in comparison to ketoconazole (KTZ) (IC50 = 3.76 μM against 17α-OHase and IC50 = 1.66 μM against lyase). Modelling of these compounds suggests that the length of the alkyl chain enhances the interaction between the inhibitor and the area of the active site corresponding to the C(3) area of the steroid backbone, thereby increasing potency.
- Patel, Chirag H.,Dhanani, Sachin,Owen, Caroline P.,Ahmed, Sabbir
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p. 4752 - 4756
(2007/10/03)
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- Mitsunobu alkylation of imidazole: A convenient route to chiral ionic liquids
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The Mitsunobu protocol offers a convenient route from imidazole to N-alkyl-substituted imidazoles, precursors to imidazolium-based ionic liquids, and is particularly useful for preparing chiral ionic liquids.
- Kim, Eun Jin,Ko, Soo Y.,Dziadulewicz, Edward K.
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p. 631 - 633
(2007/10/03)
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- N-substituted-imidazoles as inhibitors of nitric oxide synthase: A preliminary screening
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Identification of potent and selective inhibitors of inducible or neuronat nitric oxide synthase (NOS) is of great interest because of their therapeutic potential for treatment of diseases mediated by overproduction of nitric oxide. Imidazole derivatives
- Salerno,Sorrenti,Guerrera,Sarva,Siracusa,Di Giacomo,Vanella
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p. 685 - 690
(2007/10/03)
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- Influence of some novel N-substituted azoles and pyridines on rat hepatic CYP3A activity
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A series of N-substituted heteroaromatic compounds structurally related to clotrimazole was synthesized, and the effects of these compounds on ethosuximide clearance in rats were determined as a measure of their abilities to induce cytochrome P4503A (CYP3A) activity. Ethosuximide clearance and in vitro erythromycin N-demethylase activity were shown to correlate. In this series, imidazole or other related heteroaromatic 'head groups' were linked to triphenylmethane or other phenylmethane derivatives. Within the series, it was found that 1-triphenylmethane-substituted imidazoles elicited the greatest increase in CYP3A activity, and that among the triphenylmethyl-substituted imidazoles, the highest activities were achieved by the substitution of F- or Cl- in either the meta or para position of one of the phenyl rings. Diphenylmethylsubstituted pyridine was effectively devoid of activity. Compounds eliciting the largest increase in CYP3A activity (viz. 1-[(3-fluorophenyl)diphenylmethyl]imidazole, 1-[(4- fluorophenyl)diphenylmethyl]imidazole, and 1-[tri-(4- fluorophenyl)methyl]imidazole) produced little or no increase in ethoxyresorufin O-dealkylase (EROD) activity (i.e. CYP1A), whereas benzylimidazole, which elicited only a small increase in CYP3A activity, produced an almost 9-fold increase in CYP1A activity. For a series of eleven compounds exhibiting a wide range of influence on CYP3A activity, a positive correlation was found between ethosuximide clearance and hepatic CYP3A mRNA levels.
- Slama, James T.,Hancock, Julie L.,Rho, Taikyun,Sambucetti, Lidia,Bachmann, Kenneth A.
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p. 1881 - 1892
(2008/04/18)
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- Imidazo[2,1-b]benzazepine derivatives, compositions and method of use
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The present invention is concerned with novel imidazo[2, 1-b][3]benzazepines of formula STR1 the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein each of the dotted lines independently represents an optional bond; R1 represents hydrogen, halo, C1-4 alkyl or C1-4 alkyloxy; R2 represents hydrogen, halo, C1-4 alkyl or C1-4 alkyloxy; R3 represents hydrogen, C1-4 alkyl, ethenyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, C1-4 alkyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, hydroxyC1-4 alkyl, formyl or hydroxycarbonyl; R4 represents hydrogen, C1-4 alkyl, hydroxyC1-4 alkyl, phenyl or halo; R5 represents hydrogen, C1-4 alkyl or halo; L represents hydrogen; C1-6 alkyl; C1-6 alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C1-4 alkyloxy, hydroxycarbonyl, C1-4 alkyloxycarbonyl, C1-4 alkyloxycarbonyl-C1-4 alkyloxy, hydroxycarbonylC1-4 alkyloxy, C1-4 alkyloxycarbonylamino, C1-4 alkylaminocarbonyl, C1-4 alkylaminocarbonylamino, C1-4 alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C1-6 alkyl substituted with both hydroxy and aryloxy; C3-6 alkenyl; C3-6 alkenyl substituted with aryl; or, L represents a radical of formula --Alk--Y--Het1 (a-1),--Alk--NH--CO--Het2 (a-2)or --Alk--Het3 (a-3); provided that 6,11-dihydro-11-(4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine is ecxluded, which are useful antiallergic compounds. Compositions comprising said compounds, methods of using and processes for preparing the same.
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- Syntheses of 1-substituted 1,2,4-triazoles, imidazoles and benzimidazoles
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Substituted 2-phenethyl-1,2,4-triazoles, 1-phenethylimidazoles 3 and 1-phenethylbenzimidazoles 5 were synthesized from the reaction of compound 8 with tri-n-butyltin hydride in good yield. The reaction of substituted-2-phenethyl halide with 1H-1,2,4-triaz
- Sharifian,Parang,Zorrieh-Amirian,Nazarinia,Shafiee
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p. 1421 - 1423
(2007/10/02)
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- An improved and convenient procedure for the synthesis of 1-substituted imidazoles
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1-Protected imidazoles, such as 1-acetyl- and 1-benzoylimidazoles, react with various halides, such as benzyl, allyl, α-keto, and alkyl halides, to give 1-protected-3-substituted imidazolium salts in high yields. The resultant imidazolium salts are easily deprotected by treatment with water or alcohols to give the corresponding 1-substituted imidazoles in excellent yields. In this reaction the yields of 1-substituted imidazoles vary with the kinds of halides used and/or with the protecting groups, and the yields increase in the following order: benzyl halides≥allyl halides~α-keto halides>alkyl halides, and acetyl≥benzoyl>ethoxycarbonyl>diethoxymethyl>trimethylsilyl>tosyl.
- Kamijo,Yamamoto,Harada,Iizuka
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p. 1213 - 1221
(2007/10/02)
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