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A simple and efficient method was developed for the synthesis of pyrazole derivatives via a one-pot reaction of 1,3-diketone and substituted hydrazines in the presence of nano-SnCl4/SiO2 as a mild catalyst. A series of some pyrazole derivatives (P1-P11) was synthesized and evaluated as antifungal and anti-cancer agents. Compounds P10 and P11 were demonstrated. The antimicrobial activities of the synthetic compounds showed that compounds P10 and P11 most excellently inhibited the growth of dermatophytes or Aspergillus species, respectively. Therefore, the cytotoxic activities of these compounds on two human cancer cell lines, A549 (lung cancer) and MCF-7 (breast cancer) were further assessed. Hence, results demonstrated that beside antifungal activity, P10 had also desirable cytotoxic effect on investigated cancerous cell lines, even higher than cisplatin.

Two novel series of quinazolinone–pyrimidine (series a: 9a–9i) and benzyl-pyrimidine hybrids (series b: 12a–12c) were designed, synthesized and characterized by spectroscopic methods. The dipeptidyl peptidase-4 inhibition potencies of these compounds were assessed through a MAK 203 kit. Compound 9e was found to be the most potent agent with an IC50 value of 34.3 ± 3.3 μM. A kinetic study revealed that it acted as a competitive inhibitor. Molecular modeling of these compounds was in agreement with the in vitro results. Due to the crucial role of dipeptidyl peptidase-4 in cancer therapy, the cytotoxic activities of the compounds were also evaluated against three cancerous cell lines (HT-29, SW1116 and A549). Almost all the compounds displayed better antiproliferative activity on colon cancer cell lines (HT-29 and SW1116) compared to a lung cancer cell line (A549). Compounds 9e and 12c exhibited significant activity toward the HT-29 cell line with an IC50 of 10.67 ± 0.3 μM and 27.9 ± 6.5 μM in comparison to sitagliptin and cisplatin as a positive control, respectively. Among the different cells, the compounds showed the best inhibitory effects on HT-29, which was compatible with the greater expression of the dipeptidyl peptidase-4 marker detected by flow cytometry in this cell line. Further studies on the hit compounds (9e and 12c) through cell cycle and apoptosis assays also showed that these compounds could induce cell death by apoptosis or arrest cells in the G2/M phase. Accordingly, the results imply that 9e is a potent inhibitor of dipeptidyl peptidase-4 with efficient anti-cancer activity and could play a role as a cytotoxic agent in colorectal cancer.

Aims: Isatin is a honored scaffold and one of the most favorable class of heterocyclic systems that possesses many interesting biological activities and well-tolerated in humans. Here a series of fifteen spirooxindole-4H-pyran derivatives containing both isatin and pyran moieties (ICa-ICo) will be examine for their anti-cancer activity. Study Design: Cytotoxic evaluation of some spirooxindole-4H-pyran derivatives in two cancerous cell lines. Place and Duration of Study: Pharmaceutical Science Research Center and Shiraz Institute for Cancer Research, Medical School in Shiraz University of Medical Sciences, Shiraz, Iran, between June 2018 and July 2019. Methodology: MTT assay was used to evaluate the cytotoxic activities of these compounds. The anticancer properties of the tested compounds were determined using A549 and MCF-7 cell lines. Results: Among the tested compounds ICc, ICd and ICf showed the best cytotoxic activities against both cancerous cell lines. Compounds ICh and ICj showed desirable cytotoxic activities against A549 cell line. Compound ICb showed desirable cytotoxic activities against MCF-7 cell line. Conclusion: We conclude that the isatin-linked pyran analog can serve as a prototype molecule for further development of a new class of anticancer agents.

The concept of green chemistry has made significant impact on many frontages including the use of green solvents or sustainable catalyst materials. Benzimidazole ring is an important nitrogen-containing heterocyclic, which exhibits a broad spectrum of bioactivities and are widely utilized by the medicinal chemists for drug discovery. A simple and efficient method was developed for the synthesis of some benzimidazole derivatives via reaction of o-phenylenediamine and substituted aldehydes in the presence of nano-SnCl4/SiO2 as a mild catalyst. Ten 2-substituted benzimidazole compounds (J1-J10) were synthesized. All compounds were evaluated against different species of yeasts and filament fungi using broth micro dilution method as recommended by clinical and laboratory standard institute. Among these compounds, the active ones were chosen for their cytotoxic activities evaluation against MCF-7 and A549 cell lines using MTT method. Compound J2 showed the best antifungal activity against all tested species. Compounds J5-J7 had also desirable antifungal activities. Our cytotoxic results were also similar to the antifungal activities except for J7 which had no cytotoxic activity.

Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry through wide range of activities, high efficacy, and good tolerability and oral availability. Furthermore, azole derivatives have engrossed attentiveness as potent antimicrobial agents. Introduction: The purpose of this review is to execute an overview of the pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole and tetrazole which possessed antimicrobial activity from 2016 to 2020 as well as all of our publication in this field. In addition, we discussed the relationship between the structure and activity and molecular docking studies of the azole derivatives to provide key features and useful information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi such that E. coli and C. albicans were common in all of these studies. Results: The comparison of reported MIC showed that fluconazole base structures were the most active ones as antifungal agents and triazole derivatives bearing nitrophenyl and coumarin moieties had the most antibacterial activity. Conclusion: Triazole and imidazole scaffolds are more important in the design of antimicrobial compounds than other azole derivatives like benzimidazole or tetrazole. All the most active compounds fulfilled the Lipinski rules.

Natural halogenated phenolic compounds are unique bioactive structures which share features and physicochemical properties with thyroid hormones, who are essential regulators of neurological development and metabolism processes. Also, these structures can be used as natural antioxidants to minimize the diseases related to oxidative stress. In this work, the binding affinity of 32 natural and synthetic halogenated bisphenols were investigated on thyroid hormone receptor-β (THR-β) using the molecular docking, MM/GBSA, molecular dynamics, and a rigorous three-layer ONIOM ((M06-2X/6-31G*:PM6:AMBER) calculation. The desirable potency is observed for binding of selected compounds to THR-β. The Met313, Asn331, and His435 are the main interacting residues in the binding cavity which involved in the hydrogen and halogen bond interactions with the ligands. The most potent candidate on binding to the active site of THR-β is presented with respect to the results of mentioned calculations. Moreover, the antioxidant activity of compounds has been investigated using the quantum mechanical calculations. The electrostatic potential surfaces illustrate well the antioxidant capacity of compounds. The halogen substituents increase the antioxidant activity of the most stable conformers. The position and number of OH groups are crucial factors which affect the activity, whereas two adjacent hydroxyl groups enhance the antioxidant activity of selected compounds. Communicated by Ramaswamy H. Sarma

New gold(I) thiolate complexes [(PPh2py)Au(SR)] (PPh2py = 2-(diphenylphosphino)pyridine and SR = the deprotonated form of pyridine-2-thiol (HSpy, 1a), pyrimidine-2 thiol (HSpyN, 1b), benzothiazole-2-thiol (HSbt, 1c) and 2-thiazoline-2-thiol (HSt, 1d)) were prepared by the reaction of chloro gold complex [(PPh2py)AuCl], A, with the corresponding in situ generated thiolate salt (through a nucleophilic substitution reaction) under inert conditions. All complexes are characterized by NMR spectroscopy and the structures of 1b and 1d were further identified by single crystal X-ray determination. An in vitro cytotoxicity evaluation against five human cancer cell lines including A549 (nonsmall cell lung cancer), SKOV3 (human ovarian cancer), MCF-7 (human breast cancer), SW1116 (colon cancer) and HeLa (cervical cancer) demonstrated the promising antitumor effects of 1b in comparison with standard auranofin and cisplatin. The effects of these compounds on the proliferation of non-tumoral breast cell line MCF-12A showed good selectivity among tumorigenic and non-tumorigenic cell lines. The results illustrated that 1b effectively produces cell death by inducing apoptosis in the MCF-7 human breast cancer cell line. These complexes inhibit both cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases as well as glutathione reductase (GR).

The complex [(PhCH2NC)AuCl], 1, was prepared by the reaction of [(Me2S)AuCl], A, with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by potassium benzothiazole-2-thiolate (Kbt) and potassium benzoimidazole-2-thiolate (Kbi) to afford complexes (PhCH2NC)Au(κ1-S-bt)], 2a and (PhCH2NC)Au(κ1-S-bi)], 2b, respectively, which were characterized by NMR spectroscopy. The cytotoxic activities of 2a and 2b were evaluated against three human cancer cell lines, including A549 (lung), SKOV3 (ovary), and MCF-7 (breast). Our results indicated that 2a exhibited comparable cytotoxicity on investigated cell lines with cisplatin. It showed a good anti-proliferative activity with IC50 of 19.46, 11.76 and 13.27 μM against A549, SKOV3 and MCF-7 cell lines, respectively. The effects of these complexes on the proliferation of the non-tumorigenic epithelial breast cell line (MCF-10A) showed their good selectivity between the tumorigenic and non-tumorigenic cell lines. Molecular docking simulation studies were also conducted to determine the specific binding site and binding mode of the synthesized gold complexes to DNA and thioredoxinreductase (TrxR) as their proposed targets.

In order to show antiproliferation and cancerous cell growth inhibition of quinazoline derivatives, a series of 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones (H1–H11) were synthesized. In vitro cytotoxic activities were evaluated against three human cancer cell lines: A549, MCF-7 and SW1116 using colorimetric MTT assay. Comparing their effects together and with cisplatin as a positive control indicated that H3, H5 and H6 exhibited better antitumor activities on A549 cell line with IC50 values less than 10 μM versus 12 μM for cisplatin. In the case of MCF-7 and SW1116 cell lines, almost all compounds displayed better cytotoxic activities than cisplatin. Molecular docking studies were applied on epidermal growth factor receptor (EGFR) as the main target of quinazoline scaffolds in cancer therapy to predict the binding energies, binding modes and orientation of these ligands toward the active site of the receptor. In silico physicochemical parameters and ADMET profiling calculations also were done. All compounds showed lower binding energies than erlotinib, the inhibitor of EGFR. Taken together, our findings showed potential anticancer effect of quinazoline compounds bearing various phenyl ring substitutions.

Spired by the chemical structure of Cilostazol, a selective phosphodiesterase 3A (PDE3A) inhibitor, several novel hybrid compounds of nucleobases (uracil, 6-azauracil, 2-thiuracil, adenine, guanine, theophylline and theobromine) and tetrazole were designed and successfully synthesized and their inhibitory effects on PDE3A as well as their cytotoxicity on HeLa and MCF-7 cancerous cell lines were studied. Obtained results show the linear correlation between the inhibitory effect of synthesized compounds and their cytotoxicity. In some cases, the PDE3A inhibitory effects of synthesized compounds are higher than the Cilostazol. Besides, compared to a standard anticancer drug methotrexate, some of the synthesized compounds showed the higher cytotoxicity against the HeLa and MCF-7 cancerous cell lines.

6-Methoxy-2-[(E)-Aryliminomethyl]-phenol (Aryl = Phenyl; 2,6-dimethyl; 2,6-diisopropylphenyl; 2,6-dichlorophenyl), comprising L1–L4 ligands, and palladium complexes [Pd(Ln)2, n = 1–4] have been synthesized. The geometries of the [Pd(Ln)2] complexes were derived from single X-ray crystallography experiments. The central Pd(II) ion is four-coordinated and surrounded by N2O2 environment, adopting a square planar geometry. The ligand is bidentate, coordinating via imine nitrogen and phenolate oxygen atoms to the metal center. Analysis of the valence geometry within the phenolate rings suggests that in all complexes, the O1–C1 has a double bond character. FT-IR, 1H, 13C NMR and single X-ray crystal structures were reported. The cytotoxicity effect of four Pd(II) complexes was assessed on three cancerous cell lines: MCF-7 (breast carcinoma), A549 (lung carcinoma) and SKOV3 (ovarian carcinoma) and compared with that for cis-platin. One out of four metal complexes, Pd(L1)2, exhibited the highest anti-proliferative activity on three investigated cancerous cells lines which is more effective than cis-platin. The results showed that this complex could effectively induce apoptotic death in cancerous cells, probably due to direct interaction by cellular DNA.

Herein, new Pt(II) complexes [R′2Pt(CNR)2] (1a–c; R′ = Me and 2a–c; R′ = p-tolyl) were synthesized by the reaction of the precursor complexes cis,cis-[Me2Pt(μ-SMe2)2PtMe2], A, and cis-[(p-tolyl)2Pt(SMe2)2], B, with four and two equivalents of different types of isocyanide ligands (CNR; R = a; t-butyl, b; benzyl, and c; cyclohexyl isocyanide), respectively. All complexes were characterized by FTIR and NMR spectroscopies, and the structure of 2b was confirmed by single-crystal X-ray determination. The evaluation of the cytotoxicity of 1a–c and 2a–c against three human cancer cell lines, namely A549 (non-small cell lung cancer cell line), SKOV3 (human ovarian cancer cell line), and MCF-7 (human breast cancer cell line), revealed promising antitumor activities for 1b and 2a in comparison with that of the standard cisplatin. Moreover, 1b effectively rendered apoptosis-inducing activities to the MCF-7 cancer cell line. The electrophoresis mobility shift assays on plasmids as well as molecular docking studies on DNA structures effectively revealed the specific binding site, binding mode, and the best orientation of the complexes to DNA.

Aims: Recently the use of antifungal drugs in human medicine has been increased, especially with the advent of AIDS epidemic. The extensive use of antifungal drugs and their resistance against fungal infections have led to the discovery of new antimicrobial compounds. Despite the growing list of azole drugs, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. Also, chemotherapy for cancer is frequently limited by organ toxicities and emergence of drug resistance in tumor cells. So efforts have focused on the development of new, less toxic, and more effective antifungal and cytotoxic agents. Study Design: Preparation of several 2-arylquinazolinones with both antifungal and cytotoxic activities. Place and Duration of Study: Department of Medicinal Chemistry, Department of Medical Mycology and Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran, from October 2016 to September 2017. Methodology: Several synthetic analogues of 2-arylquinazolinones have been developed aiming at drugs with high potency and diminished toxicity. Thus, 2-arylquinazolinones (1b-12b) are prepared according to literature. The antimicrobial activities of these compounds against different species of microorganisms including fungi, gram positive and gram negative bacteria are evaluated. Broth micro-dilution method as recommended by clinical and laboratory standard institute (CLSI) was used for this purpose. We also evaluated the cytotoxic activities of the compounds against three human cancer cell lines (MCF-7, A549 and SKOV3) using colorimetric MTT cytotoxic assay. The specific binding mode of synthetic 2-arylquinazolinones have been also indicated by molecular modelling studies to show the interactions and binding orientation of compounds to CYP51 active site. Results: Compound 1b showed desirable activities against bacteria as well as yeasts and filaments fungi. Compounds 2b, 7b, 8b and 9b can inhibit the growth of different yeasts with acceptable MIC. The cytotoxic results showed compounds 7b, 8b, 9b and 10b had partial inhibitory effects on cancer cell lines in particular lung adenocarcinoma. Conclusion: 2-arylquinazolinones are respectable candidate for further studies in biological research.

Mononuclear complexes [Pt(ppy)(S∧S)] (1a, S∧S = O,O′-di(cyclohexyl)dithiophosphate (ctp); 2a, S∧S = O,O′-di(butyl)dithiophosphate (btp)) and [Pt(bzq)(S∧S)] (1b, S∧S = ctp; 2b, S∧S = btp) have been prepared by the reaction of precursor complexes [Pt(C∧N)Cl(dmso)], C∧N = deprotonated form of 2-phenylpyrdine (ppy) and 7,8-benzoquinoline (bzq), and potassium salt of S∧S ligands. All complexes were characterized by NMR spectroscopy, and the structure of 2b was further identified by single crystal X-ray determination. Although the complexes are not luminescent in solution at ambient temperature, they become strong emissive materials (bright green) in solid state (at room temperature) with high quantum yields and long lifetimes in the microsecond domain. In frozen glass state or at low temperature (solid state), these complexes become better emissive in relation to room temperature. UV–vis spectra, supported by TD-DFT calculations, indicate that 1ILCT (intraligand charge transfer) predominates over the other tra...

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.

Background and purpose: Synthesis and investigation of pharmacological activity of novel compounds are time and money-consuming. However, computational techniques, docking, and in silico studies have facilitated drug discovery research to design pharmacologically effective compounds. Experimental approach: In this study, a series of quinazoline derivatives were applied to quantitative structure-activity relationship (QSAR) analysis. A collection of chemometric methods were conducted to provide relations between structural features and cytotoxic activity of a variety of quinazoline derivatives against breast cancer cell line. An in silico -screening was accomplished and new impressive lead compounds were designed to target the epidermal growth factor receptor (EGFR)-active site based on a new structural pattern. Molecular docking was performed to delve into the interactions, free binding energy, and molecular binding mode of the compounds against the EGFR target. Findings/Results: A comparison between different methods significantly indicated that genetic algorithm-partial least-squares were selected as the best model for quinazoline derivatives. In the current study, constitutional, functional, chemical, resource description framework, 2D autocorrelation, and charge descriptors were considered as significant parameters for the prediction of anticancer activity of quinazoline derivatives. In silico screening was employed to discover new compounds with good potential as anticancer agents and suggested to be synthesized. Also, the binding energy of docking simulation showed desired correlation with QSAR and experimental data. Conclusion and implications: The results showed good accordance between binding energy and QSAR results. Compounds Q 1 -Q 30 are desired to be synthesized and applied to in vitro evaluation.

Alzheimer’s disease (AD) as the most common form of dementia in aged people, is an intricate neurodegenerative disease. Therefore, a novel strategy so-called multi-target-directed ligand has received much attention for the effective treatment of AD. In this study a series of novel carbazole-benzylpiperidine hybrids 9a-m was designed, synthesized and evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors. Moreover, some of these compounds were evaluated for anti β-secretase (BACE1) activity and metal chelation properties. Among the synthesized compounds, compounds 9b (IC50 = 16.5 μM for AChE and IC50 = 0.59 μM for BuChE) and 9c (IC50 = 26.5 μM for AChE and IC50 = 0.18 μM for BuChE) showed the highest inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Furthermore, these compounds (9b and 9c) displayed interaction with Zn2+ ion and compound 9c showed moderate inhibitory activity against BACE1 (24.5% at 50 μM). Kinetic and docking studies exhibited that these compounds likely act as a non-competitive inhibitor able to interact with the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase simultaneously.

Dichloroacetate (DCA) as a mitochondria-targeting small molecule, through inhibition of pyruvate dehydrogenase kinases (PDK1-4), promotes mitochondria-regulated apoptosis and hence, inhibits tumour growth and reduces its proliferation. In this study, a series of novel N-aryl-2,2-dichloroacetamide and aryl-2,2-dichloroacetate derivatives were designed and synthesized. Their cytotoxic activities against various human cancer cell lines including A549, HCA-7, MCF-7, MDA-MB-231, KB and SKOV3 were evaluated. These compounds showed satisfactory potencies with much higher anticancer activity than the parent compound DCA, against the studied cancer cell lines. Molecular docking studies were also done to find their binding site and types of their interactions with PDKs isoenzymes. Among the synthesized compounds, 2,2-dichloro-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide (f1) can also induce A549 cells apoptosis. Therefore, compound f1 might have a potential value for further study in drug development. QSAR studies of this class of compounds were also explored using a collection of chemometrics methods.

The salt metathesis reaction of sodium precursors, Na[H2B(mb)2] (Hmb = 2-mercapto-benzimidazole) and Na[H2B(mbt)2] (Hmbt = 2-mercapto-benzothiazole) of bipodal scorpionate ligands with Cu(OAc)2, CoCl2 and NiBr2 afforded six metal complexes, 1–6. The metal complexes were characterized using a combination of HR ESI-MS spectrometry, elemental analysis and IR spectroscopy. The cytotoxicity effect of these complexes was assessed on three human cancerous cell lines: MCF-7 (breast carcinoma), A549 (lung carcinoma) and SW1116 (colon adenocarcinoma) and compared with that for cis-platin. Our results indicated that all complexes had desirable antitumor activities (

Dichloroacetate (DCA) is a simple and small anticancer drug that arouses the activity of the enzyme pyruvate dehydrogenase (PDH) through inhibition of the enzyme pyruvate dehydrogenase kinases (PDK1-4). DCA can selectively promote mitochondria-regulated apoptosis, depolarizing the hyperpolarized inner mitochondrial membrane potential to normal levels, inhibit tumor growth and reduce proliferation by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis. In this study, a series of DCA analogues were applied to quantitative structure–activity relationship (QSAR) analysis. A collection of chemometrics methods such as multiple linear regression (MLR), factor analysis–based multiple linear regression (FA-MLR), principal component regression (PCR), and partial least squared combined with genetic algorithm for variable selection (GA-PLS) were applied to make relations between structural characteristics and cytotoxic activities of a variety of DCA analogues. The best multiple linear regression equation was obtained from genetic algorithms partial least squares, which predict 90% of variances. Based on the resulted model, an in silico-screening study was also conducted and new potent lead compounds based on new structural patterns were designed. Molecular docking as well as protein ligand interaction fingerprints (PLIF) studies of these compounds were also investigated and encouraging results were acquired. There was a good correlation between QSAR and docking results.

The molecular basis of Alzheimer’s disease (AD) is a critical aspect for understanding the role of A β fibrils in neurotoxicity and for designing therapeutic strategies against AD. Molecular insight into the prevention of A β peptide aggregates in the presence of P7C3, a derivative of dibromocarbazole, molecule is presented for the first time. P7C3 protects newborn neurons from apoptotic cell death, but mechanistic details are lacking. The ability of P7C3 to prevent the onset or to slow the progression of the Alzheimer’s disease was studied by using molecular dynamics (MD) simulations. Two different mechanisms were considered: the disruption of A β aggregation by direct binding of P7C3 to A β and alterations in amyloid precursor protein processing through the inhibition of β -secretase. The results indicate that P7C3 molecule can efficiently bind to the β -secretase active site. The direct interactions of P7C3 with A β peptide are also important but in a lesser extent.

Recently the quinazoline derivatives have attracted much attention for their anticancer properties. In this study a series of new brominated quinazoline derivatives (1a-1g) were synthesized in two steps. In the first step we used N-bromosuccinimide to brominate the anthranilamid. Then in the second step we closed the quinazoline ring by different aromatic aldehydes. Our aldehydes contain different electron donating or electron withdrawing groups at different positions of the aromatic ring. The chemical structures of products were confirmed by spectroscopic methods such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The cytotoxic activities of the compounds were assessed on three cancerous cell lines including MCF-7, A549, and SKOV3 using colorimetric MTT cytotoxic assay in comparison with cisplatin as a standard drug. Our results collectively indicated that 1f and 1g, exhibited the best anti-proliferative activities on three investigated cancerous cell lines.

A convenient and highly efficient protocol for one-pot synthesis of some novel N-heterocycle methyl-O-oxime ethers is described. In this method, three-component coupling of different types of ketoximes, with methylene iodide and nitrogen heterocy- cles, including imidazoles, benzimidazole, benzotriazole, and theo- phylline in the presence of an equimolar mixture of K2CO3/Et3N in refluxing MeCN furnished the corresponding N-heterocycle meth- yl-O-oxime ethers in good yields. This methodology is highly effi- cient for the synthesis of various structurally diverse N-heterocycle methyl-O-oxime ethers. The results of quantum mechanical studies on reaction intermediates are discussed.

A convenient method is developed for the coupling of ketoximes, nitrogen heterocycles, and methylene iodide.