The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Olga García Mancheño - One of the best experts on this subject based on the ideXlab platform.
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Mild Radical Oxidative sp3-Carbon–Hydrogen Functionalization: Innovative Construction of Isoxazoline and Dibenz[b,f]oxepine/azepine Derivatives
Synlett, 2016Co-Authors: Andrea Gini, Olga García MancheñoAbstract:Direct carbon–hydrogen bond functionalization has emerged as a powerful synthetic method for the straightforward and modular functionalization of organic molecules. In this account, we described our latest contributions in the area of oxidative sp3-carbon–hydrogen bond functionalization using mild radical oxidants for the construction of structurally important heterocycles. We have developed two new methodologies in which a new class of substrate and an uncommon nucleophilic reagent have been introduced to the existing palette of reaction partners for oxidative carbon–hydrogen functionalization. To achieve these results, the 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) radical and a benzoyl peroxide/copper(I) system have been employed as oxidants for the dehydrogenative one-pot synthesis of N-alkoxycarbonyl-protected isoxazolines from hydroxylamines and for the synthesis of dibenz[b,f]oxepines, dibenzo[b,f]thiepines, and dibenz[b,f]azepines from simple xanthenes, thioxanthenes, and acridanes, respectively. 1 Introduction 2 2,2,6,6-Tetramethylpiperidinyloxyl-Mediated Dehydrogenative Formation and Trapping of Unstable Nitrones: Synthesis of N-Alkoxycarbonyl-Protected Isoxazoline Derivatives 3 Oxidative sp3-Carbon–Hydrogen Bond Functionalization and Ring Expansion with Trimethylsilyldiazomethane: Synthesis of Dibenzoxepines, Dibenzothiepines, and Dibenzazepines 4 Conclusions and Outlook
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mild radical oxidative sp3 carbon hydrogen functionalization innovative construction of isoxazoline and dibenz b f oxepine azepine derivatives
Synlett, 2016Co-Authors: Andrea Gini, Olga García MancheñoAbstract:Direct carbon–hydrogen bond functionalization has emerged as a powerful synthetic method for the straightforward and modular functionalization of organic molecules. In this account, we described our latest contributions in the area of oxidative sp3-carbon–hydrogen bond functionalization using mild radical oxidants for the construction of structurally important heterocycles. We have developed two new methodologies in which a new class of substrate and an uncommon nucleophilic reagent have been introduced to the existing palette of reaction partners for oxidative carbon–hydrogen functionalization. To achieve these results, the 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) radical and a benzoyl peroxide/copper(I) system have been employed as oxidants for the dehydrogenative one-pot synthesis of N-alkoxycarbonyl-protected isoxazolines from hydroxylamines and for the synthesis of dibenz[b,f]oxepines, dibenzo[b,f]thiepines, and dibenz[b,f]azepines from simple xanthenes, thioxanthenes, and acridanes, respectively. 1 Introduction 2 2,2,6,6-Tetramethylpiperidinyloxyl-Mediated Dehydrogenative Formation and Trapping of Unstable Nitrones: Synthesis of N-Alkoxycarbonyl-Protected Isoxazoline Derivatives 3 Oxidative sp3-Carbon–Hydrogen Bond Functionalization and Ring Expansion with Trimethylsilyldiazomethane: Synthesis of Dibenzoxepines, Dibenzothiepines, and Dibenzazepines 4 Conclusions and Outlook
Andrea Gini - One of the best experts on this subject based on the ideXlab platform.
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Mild Radical Oxidative sp3-Carbon–Hydrogen Functionalization: Innovative Construction of Isoxazoline and Dibenz[b,f]oxepine/azepine Derivatives
Synlett, 2016Co-Authors: Andrea Gini, Olga García MancheñoAbstract:Direct carbon–hydrogen bond functionalization has emerged as a powerful synthetic method for the straightforward and modular functionalization of organic molecules. In this account, we described our latest contributions in the area of oxidative sp3-carbon–hydrogen bond functionalization using mild radical oxidants for the construction of structurally important heterocycles. We have developed two new methodologies in which a new class of substrate and an uncommon nucleophilic reagent have been introduced to the existing palette of reaction partners for oxidative carbon–hydrogen functionalization. To achieve these results, the 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) radical and a benzoyl peroxide/copper(I) system have been employed as oxidants for the dehydrogenative one-pot synthesis of N-alkoxycarbonyl-protected isoxazolines from hydroxylamines and for the synthesis of dibenz[b,f]oxepines, dibenzo[b,f]thiepines, and dibenz[b,f]azepines from simple xanthenes, thioxanthenes, and acridanes, respectively. 1 Introduction 2 2,2,6,6-Tetramethylpiperidinyloxyl-Mediated Dehydrogenative Formation and Trapping of Unstable Nitrones: Synthesis of N-Alkoxycarbonyl-Protected Isoxazoline Derivatives 3 Oxidative sp3-Carbon–Hydrogen Bond Functionalization and Ring Expansion with Trimethylsilyldiazomethane: Synthesis of Dibenzoxepines, Dibenzothiepines, and Dibenzazepines 4 Conclusions and Outlook
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mild radical oxidative sp3 carbon hydrogen functionalization innovative construction of isoxazoline and dibenz b f oxepine azepine derivatives
Synlett, 2016Co-Authors: Andrea Gini, Olga García MancheñoAbstract:Direct carbon–hydrogen bond functionalization has emerged as a powerful synthetic method for the straightforward and modular functionalization of organic molecules. In this account, we described our latest contributions in the area of oxidative sp3-carbon–hydrogen bond functionalization using mild radical oxidants for the construction of structurally important heterocycles. We have developed two new methodologies in which a new class of substrate and an uncommon nucleophilic reagent have been introduced to the existing palette of reaction partners for oxidative carbon–hydrogen functionalization. To achieve these results, the 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) radical and a benzoyl peroxide/copper(I) system have been employed as oxidants for the dehydrogenative one-pot synthesis of N-alkoxycarbonyl-protected isoxazolines from hydroxylamines and for the synthesis of dibenz[b,f]oxepines, dibenzo[b,f]thiepines, and dibenz[b,f]azepines from simple xanthenes, thioxanthenes, and acridanes, respectively. 1 Introduction 2 2,2,6,6-Tetramethylpiperidinyloxyl-Mediated Dehydrogenative Formation and Trapping of Unstable Nitrones: Synthesis of N-Alkoxycarbonyl-Protected Isoxazoline Derivatives 3 Oxidative sp3-Carbon–Hydrogen Bond Functionalization and Ring Expansion with Trimethylsilyldiazomethane: Synthesis of Dibenzoxepines, Dibenzothiepines, and Dibenzazepines 4 Conclusions and Outlook
Ben Green - One of the best experts on this subject based on the ideXlab platform.
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zotepine a clinical review
Expert Opinion on Drug Metabolism & Toxicology, 2009Co-Authors: Ben GreenAbstract:Zotepine is a second generation antipsychotic drug, a substituted Dibenzothiepine tricyclic molecule, with effects on dopamine, serotonin and noradrenaline receptors. This article reviews the relevant research studies on the drug based on a search of numerous medical databases for research and literature concerning zotepine and adverse reactions reported to the UK Medicines and Healthcare Products Regulatory Agency. There are double-blind trials demonstrating zotepine as an efficacious antipsychotic with a safe side effect profile that compares favourably with other atypical antipsychotics with regard to metabolic effects and movement disorders. There are some open label studies suggesting usefulness in treatment resistant schizophrenia, but larger, double-blind studies are required.
Carol Davila - One of the best experts on this subject based on the ideXlab platform.
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new Dibenzothiepine sulfones synthesis and structure elucidation
2013Co-Authors: Camelia Elena Stecoza, Corina Ilie, Constantin Draghici, Miron Teodor Caproiu, Carol DavilaAbstract:The interest for the tricyclic compounds having Dibenzothiepine structure has been heightened during the last years due to their broad spectrum of biological activities. Dibenzothiepine derivatives have significant psychotropic activities [1, 2], but also other important properties. Zaltoprofen is a nonsteroidal anti-inflammatory drug with powerful analgesic action [3]. Methiotepine and octochlothepine, two Dibenzothiepine antipsychotics, were found to have significant bacteriostatic activity towards M. tuberculosis, including virulent strains [4]. Some Dibenzothiepine compounds demonstrated their potential use as antiprotozoal agents [5] and more recently dibenzo[b,e]thiepines proved to be active as inhibitors of tumor necrosis factor-α (TNF- α), and therefore useful for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations [6]. Researchers have also reported [7] that some Dibenzothiepine derivatives are useful as insecticidal, acaricidal and nematicidal agents. Motivated by these findings and as part of our ongoing studies, we proposed to synthesize new biologically active dibenzo[b,e]thiepine derivatives. In previous papers we reported the synthesis and antipathogenic activity of some Dibenzothiepines, against planktonic cells and bacterial cells grown in biofilms [8-12]. We also reported the results of in silico evaluations performed on Dibenzothiepine compounds [13]. The predictions were focused on molecular descriptors relevant for quantitative estimation of penetration across various biological barriers. The results indicated a low solubility - high permeability profile, with considerable impact of gastro-intestinal, endogenous tensioactives. The predicted pharmacokinetic characteristics proved to be favorable for expressing a potential psychotropic activity for Dibenzothiepine compounds. Experimental part All chemicals used were purchased from commercial sources (Merck, Fluka, Sigma - Aldrich) and were of reagent grade. Solvents were used as received, except benzene (dried over sodium and then distilled) and pyridine (stored over potassium hydroxide and then distilled). Melting points were determined with an Electrothermal 9100 apparatus in open capillary tubes and are uncorrected. Elemental analyses were carried out using a Perkin Elmer CHNS/O Analyzer Series II 2400 apparatus, and the results were within ±0.4% of theoretical values. Thin layer chromatography (TLC) was performed on silicagel 60F254 Merck plates. For the development chloroform/ ethyl acetate (10:1) was used. The visualization was performed using an UV lamp (λ= 254nm) and iodine atmosphere. The IR spectra were recorded using a FT-IR Bruker Vertex 70 spectrometer, with horizontal device for attenuated reflectance and diamond crystal, on a spectral window ranging from 4000 to 400 cm -1 , at a spectral resolution of 2 cm -1 . The IR bands are denoted as: w- weak;
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molecular determinants of solubility in biorelevant fluids for Dibenzothiepine compounds
2013Co-Authors: Camelia Elena Stecoza, George Mihai, Magdalena Majekova, Dalia Simona Miron, Carol DavilaAbstract:The solubility profile of ten benzothiepine compounds was screened using the currently recommended fasted and fed state simulated gastric and intestinal fluids, as part of the in vitro evaluation of their biopharmaceutical properties and of the developability potential. The experimental data was compared with the previously reported in silico predictions generated on ADMET Predictor platform. The results indicated a considerable impact of the endogenous tensioactives, with maximum absorbable doses varying between 20 and 200 mg. The non-correlation between the in vitro evaluated and in silico estimates were significant, especially for the gastric media. The global solubility profile seems to indicate that the evaluated compounds have dissolution-rate limited characteristics and belong to the sub-class IIa of the Biopharmaceutical Classification System. Rezumat A fost evaluat profilul solubilităţii pentru zece compusi cu structură dibenzotiepinică utilizând medii fiziologice simulate gastrice si intestinale, pre- si postprandial, ca parte a analizei in vitro a proprietăţilor biofarmaceutice si a potenţialului de dezvoltare farmaceutică. Datele experimentale au fost comparate cu predicţiile in silico raportate anterior, generate in cadrul platformei ADMET Predictor. Rezultatele indică un impact major al compusilor tensioactivi endogeni, doza maximă absorbabilă variind intre 20 si 200 mg. Non-corelările intre datele generate in vitro si estimările in silico au fost semnificative, in special pentru mediul gastric. Profilul global al solubilităţii pare să indice o limitare cinetică a dizolvării si apartenenţa la clasa IIa a sistemului de clasificare biofarmaceutică.
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integrating the values of molecular descriptors in the prediction of biopharmaceutical properties for new compounds with Dibenzothiepine structure
2011Co-Authors: Camelia Elena Stecoza, George Mihai, Magdalena Majekova, Dalia Simona Miron, Carol DavilaAbstract:The paper presents the results of in silico evaluations performed on a group of 127 compounds with Dibenzothiepine structure. The predictions were focused on molecular descriptors relevant for quantitative estimation of penetration across various biological barriers. The results indicated a low solubility together with high permeability profile, with considerable impact of gastro-intestinal, endogenous tensioactives. The predicted pharmacokinetic characteristics are favorable for expressing a potential psychotropic activity. Rezumat Lucrarea prezintă rezultatele evaluărilor in silico efectuate asupra unui grup de 127 de compusi cu structură dibenzotiepinică. Predicţiile au vizat descriptori moleculari relevanţi pentru estimarea cantitativă a traversării prin diferite bariere biologice. Rezultatele au indicat un profil de tip solubilitate redusă - permeabilitate crescută, cu un impact considerabil al tensioactivilor endogeni prezenţi la nivelul tractului gastro-intestinal. Caracteristicile farmacocinetice prefigurate teoretic sunt favorabile pentru exprimarea unei potenţiale activităţi psihotrope.
Patrick Chene - One of the best experts on this subject based on the ideXlab platform.
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inhibition of dna helicases with dna competitive inhibitors
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Sandy Dubaele, Wolfgang Jahnke, Joseph Schoepfer, Jean Fuchs, Patrick CheneAbstract:Helicases form an attractive protein family for drug discovery because they are involved in various human diseases. In this report, we show that it is possible to inhibit both the ATPase and the helicase activities of a DNA helicase with dibenzothiepins that bind at its nucleic acid binding site. These results suggest a drug discovery strategy to inhibit DNA helicases.