China
Africa
Explore chapters and articles related to this topic
Parasympathomimetic Amines
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
The parent muscarinic agonist, after which the receptor is named, is muscarine. It is isolated from the poisonous mushroom, Amanita muscaria, but the levels are insufficient to account for the toxicity of this fungus. The toxicity is attributed to anticholinergic and hallucinogenic isoxazole derivatives. Other richer sources of muscarine include species of Inocybe and Clitocybe, poisoning by which causes symptoms that may be predicted from the muscarinic agonist activity. These include salivation and lacrymation, nausea, vomiting and abdominal pain, diarrhoea, bronchospasm, hypotension and bradycardia (slow weak pulse) and visual disturbances. Muscarine is a quaternary ammonium compound that occurs naturally as the L-(+)-isomer and is highly selective for muscarinic receptors (Table 8.2).
Isoxazolyl Penicillins: Oxacillin, Cloxacillin, Dicloxacillin, and Flucloxacillin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Oral administration of isoxazolyl penicillins may cause nausea and diarrhea, which only occasionally necessitates cessation of treatment. Antibiotic-associated colitis due to Clostridium difficile can be caused by these drugs; toxin-producing C. difficile was isolated from the feces of one child who developed watery diarrhea with i.v. oxacillin therapy, and from another child who developed diarrhea following 4 days of oral dicloxacillin (Brook, 1980).
Radiolabeled Enzyme Inhibitors for Imaging
Published in Lelio G. Colombetti, Principles of Radiopharmacology, 1979
William H. Beierwaltes, Donald M. Wieland, Dennis P. Swanson
In 1970, Goldman9 studied the tissue distribution of 17β-hydroxy-4, 4’-17α-trimethylandrost-5-en-[2,3d]-2-14C-isoxazole (isoxazole), a radiolabeled irreversible enzyme inhibitor of 3β-hydroxysteroid dehydrogenase and Δ5-4, 3-ketosteroid isomerase in the rat. Twenty-four hours after a single dose, the label was present in the adrenals, ovaries, and liver. Beyond 48 hr, the label was retained only by the adrenals and ovaries, where it remained for 13 weeks. The labeled compound, extracted from adrenal homogenates, had a mobility identical to that of standard isoxazole on silica gel in 3 chromatographic systems, and an inhibitory capacity similar to the isoxazole standard in a bacterial 3β-hydroxysteroid dehydrogenase assay system. Inhibition of enzymatic activity in vivo was directly correlated with uptake of the label. Return of enzymatic activity correlated with disappearance of label; the degree of enzymatic inhibition and amount of label in both glands attaining constant low values after about 1 month. These observations provided evidence for the specificity of action of this analog and suggested that its long-term effects are a function of its selective and tight binding to the active sites of hydrogenase and isomerase.
Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mohamed Mokhtar Mohamed Abdelahi, Youness El Bakri, Chin-Hung Lai, Karthikeyan Subramani, El Hassane Anouar, Sajjad Ahmad, Mohammed Benchidmi, Joel T. Mague, Jelena Popović-Djordjević, Souraya Goumri-Said
Indazoles correspond to isomeric chemical compounds with molecular formula C7H6N2, having a pyrazole ring condensed with a benzene ring (benzo[c]pyrazole, 1,2-benzodiazole). The indazole heterocycle is normally referred to as 1H-indazole, although it has two other potential tautomers 2H-indazole and 3H-indazole34. Isoxazolines are an important class of nitrogen and oxygen-containing heterocycles that belong to the azoles family which have much importance in the field of medicinal chemistry. Isoxazoles are considered privileged scaffolds in drug discovery and have a broad spectrum of activities, such as antiviral14, antibacterial15, antimycobacterial16, anti‐inflammatory17, and more recently, they have also demonstrated antitrypanosomal activity18.
Immunosuppression in the Management of Presumed Non-infective Uveitis; Are We Sure What We are Treating? Notes on the Antimicrobial Properties of the Systemic Immunosuppressants
Published in Ocular Immunology and Inflammation, 2020
Leflunomide was initially found to be a potent antiviral against CMV, and in due course, its efficacy against host or graft CMV was demonstrated in a clinical setting.70 It is also known to be active against Polyomaviruses, several Herpesviridae, and Respiratory syncytial virus. One clinically important polyomavirus is BK virus which induces post-graft nephritis and is an important cause of graft failure. Leflunomide and sirolimus may be synergistic in treating the virus.71 However, its mainstay is in the management of difficult (often post-transplantation) CMV disease particularly when ganciclovir-resistant, and it has a place in drug-resistant CMV retinitis.72 Although recent studies on isoxazoles and similar derivatives to leflunomide have been found to have antibacterial effects, leflunomide does not appear to have such properties. There are no known antifungal effects.
Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Paolo Guglielmi, Giulia Rotondi, Daniela Secci, Andrea Angeli, Paola Chimenti, Alessio Nocentini, Alessandro Bonardi, Paola Gratteri, Simone Carradori, Claudiu T. Supuran
The third design strategy was inspired from the findings achieved in our recent paper about a series of saccharin/isoxazole and saccharin/isoxazoline derivatives (Figure 2)42. These compounds were gifted with an isoxazole or isoxazoline linker which disconnected the methylene moiety from the phenyl ring, resulting in the strong affinity for hCA IX and hCA XII along with selectivity over hCA I and hCA II (Figure 2(A)). Thus, based on these good results, we proposed the replacement of the isoxazole “linker” with the triazole one, that resulted advantageous for some hCAs inhibitors (Figure 2(B))43–46. The triazole ring is, similar to the isoxazole one, an aromatic five-membered heterocyclic ring, even if it contains only the nitrogen heteroatom in spite of the oxygen/nitrogen ones of the isoxazole core. Moreover, it is able to establish stacking interactions in the lipophilic side of the active site as the isoxazole, and it is easy to insert through the well-known “click” azide-alkyne cycloaddition. For some of these derivatives the hydrolytic ring opening and/or the introduction of an additional methylene group between the N1 of the triazole and the phenyl ring bound to it, have also been evaluated. Indeed, the ring opening can lead to the same improvements discussed above as well as the insertion of the methylene group would increase the “flexibility” of the tail interrupting the electronic conjugation, too.