Search results for "Azepine"
showing 10 items of 266 documents
Behavioural stress reactivity in handling naive and handling-habituated adult male rats prenatally exposed to different benzodiazepine receptor agoni…
2001
Development of antimigraine transdermal delivery systems of pizotifen malate.
2015
Abstract The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seeme…
Development of Novel Benzodiazepine-Based Peptidomimetics as Inhibitors of Rhodesain from Trypanosoma brucei rhodesiense.
2020
Starting from the reversible rhodesain inhibitors 1 a-c, which have Ki values towards the target protease in the low-micromolar range, we have designed a series of peptidomimetics, 2 a-g, that contain a benzodiazepine scaffold as a β-turn mimetic; they are characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversibl…
Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antipr…
2014
Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure-activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzod…
Staphylococcus aureus alpha toxin mediates polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction.
2002
The effect of Staphylococcus aureus alpha toxin (alpha-toxin) on selectin-mediated neutrophil adhesion was investigated in polymorphonuclear leukocyte- (PMN) induced vasocontraction and endothelial dysfunction. Adherence of human PMNs to rat aortic endothelium increased significantly following stimulation of the endothelium with alpha-toxin (0.1, 0.5, and 1 microg/mL). This effect could be significantly attenuated by monoclonal antibodies directed against P-selectin or fucoidin, a carbohydrate known to block selectins. Unstimulated human PMNs (10(6)cells/mL) were added to organ chambers containing rat aortic rings stimulated with alpha-toxin (0.5 microg/mL). PMNs elicited a significant vaso…
Adding the Mureş River Basin (Transylvania, Romania) to the List of Hotspots with High Contamination with Pharmaceuticals
2020
Background: The Mureș River Basin is a long-term heavily polluted watershed, in a situation of climate changes with increasing water flow and related decreasing dilution capacity. Here, a mixture of emerging pollutants such as pharmaceuticals were targeted to reveal potential risks regarding the natural lotic ecosystems. Due to the continuous discharge into the environment, pharmaceuticals are gaining persistent organic pollutant characteristics and are considered emerging pollutants. Based on the hazard quotient, this research highlights the dangerous concentrations of carbamazepine, ibuprofen, furosemide, and enalapril in river water. Results: High levels of four pharmaceutical compounds …
GABAA-receptor Subtypes: Clinical Efficacy and Selectivity of Benzodiazepine Site Ligands
1997
The main inhibitory neurotransmitter receptor of the brain, the gamma-aminobutyric acid type A receptor (GABA[A]), mediates the actions of several classes of clinically important drugs, such as benzodiazepines, barbiturates and general anaesthetics. This review summarizes the current knowledge on how classical benzodiazepines and novel nonbenzodiazepine compounds act on the benzodiazepine site of GABA(A) receptors and on their clinical pharmacology related to anxiolytic, sedative, hypnotic and cognitive effects or side-effects. Partial agonism, receptor subtype selectivity and novel binding sites are discussed as possible strategies to develop new drugs with fewer adverse effects than are s…
Zaleplon displays a selectivity to recombinant GABAA receptors different from zolipdem, zopiclone and benzodiazepines
1999
A chemically heterogeneous group of compounds acts at the benzodiazepine (BZ) recognition site of the γ-aminobutyric acid type A (GABAA) receptor complex. Whereas most 1,4-BZs recognize all GABAA/BZ receptors with similar affinity, other compounds differentiate between the large number of native GABAA receptors which assemble from the more than 14 known subunits. Here we describe the in vitro binding properties of the BZs lorazepam and Ro 15-4513 plus the three hypnotics zaleplon, zolpidem and zopiclone to eight receptors subtypes. Lorazepam fits well into the general shceme for other 1,4-BZs with respect to its receptor subtype selectivity in spite of its clinically different use. Zaleplon…
Enantioselective addition of Et2Zn to seven‐membered cyclic imines catalyzed by a (R)-VAPOL-Zn(II) complex
2017
Various substituted dibenzo[b,f][1,4]oxazepines underwent an enantioselective alkylation with Et2Zn catalyzed by a (R)-VAPOL-Zn(II) complex. The corresponding chiral 11-ethyl-10,11-dihydrodibenzo[b,f][1,4]oxazepine derivatives were obtained with good yields and moderate enantioselectivities. This represents the first example of enantioselective addition of Et2Zn to cyclic aldimines.
ChemInform Abstract: 1-Alkyl- and Azeto[1,2-a][1,5]benzodiazepine Derivatives in the Reaction of o-Phenylenediamine with 3-(Dimethylamino)propiopheno…
2001
The reaction of o-phenylenediamine (4) with one, two or three equivalents of p-substituted 3-dimethylaminopropiophenone hydrochlorides 5a−e was studied. 4-Aryl-2,3-dihydro-1H-1,5-benzodiazepine derivatives 6a−e were obtained in good yields, along with the 1:2-adducts 7c−e and the unexpected 1:3-adducts rac-8c−e. The type of adduct formed is determined by the molar ratio of the reactants 4 and 5 and by the nature of the substituent in the para position of the propiophenone 5.