Search results for "oxadiazole"

Translational readthrough of ciliopathy genes BBS2 and ALMS1 restores protein, ciliogenesis and function in patient fibroblasts

2021

Abstract Background Ciliary dysfunction underlies a range of genetic disorders collectively termed ciliopathies, for which there are no treatments available. Bardet-Biedl syndrome (BBS) is characterised by multisystemic involvement, including rod-cone dystrophy and renal abnormalities. Together with Alstrom syndrome (AS), they are known as the ‘obesity ciliopathies’ due to their common phenotype. Nonsense mutations are responsible for approximately 11% and 40% of BBS and AS cases, respectively. Translational readthrough inducing drugs (TRIDs) can restore full-length protein bypassing in-frame premature termination codons, and are a potential therapeutic approach for nonsense-mediated ciliop…

Relaxant effect of sildenafil in the rabbit basilar artery

2005

We hypothesized that sildenafil, inhibitor of phosphodiesterase-5 (PDE-5), interacts with the nitric oxide (NO)-cGMP pathway in the cerebral arteries and shows vasoactive effects. To prove it in the isolated rabbit basilar artery, we compared the effects of sildenafil with other PDE-5 inhibitors, assessed the endothelial dependence of the vasoactive responses, and used modulators of the cGMP and cAMP signaling processes. Sildenafil (10 nM-0.1 mM) induced concentration-dependent relaxations of endothelin-1 (10 nM)-precontracted basilar artery, which were partially inhibited both in endothelium-denuded arteries and in arteries precontracted by depolarization with KCl (50 mM). Endothelin-1 (1 …

The new era of 1,2,4-oxadiazoles

2009

The synthesis, the chemical and photochemical reactivity, and the use of 1,2,4-oxadiazoles in materials and as bioactive compounds have been reviewed. The material in this survey includes some historical background, general features, state-of-the-art applications together with a critical discussion about current limitations and suggestions for future developments.

Synthesis of new fluorinated low molecular weight (LMW) gelators

2011

ChemInform Abstract: Photoinduced Molecular Rearrangements. The Photochemistry of Some 1,2, 4-Oxadiazoles in the Presence of Nitrogen Nucleophiles. F…

2010

The photochemistry of some 3,5-disubstituted 1,2,4-oxadiazoles in the presence of nitrogen nucleophiles [external, such as added amines or hydrazines, or internal, such as an o-aminophenyl moiety at C(3) of the oxadiazole ring] has been investigated. In the irradiation of 5-amino-(or 5-N-substituted amino) 3-phenyl-1,2,4-oxadiazoles in the presence of aliphatic primary amines (or ammonia), photolytic species arising from heterolytic cleavage of the ring O−N bond capture the nucleophilic reagent to give open-chain intermediates, which develop into 1,2,4-triazolin-5-ones. Similarly, irradiations of 3,5-diphenyl-, 3-methoxy-5-phenyl-, and 5-methyl-3-phenyl-1,2,4-oxadiazoles gave 1,2,4-triazole…

Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide

2012

New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivati…

On the Rearrangement in Dioxane/Water of (Z)-Arylhydrazones of 5-Amino-3-benzoyl-1,2,4-oxadiazole into (2-Aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas: …

2006

We have recently evidenced an interesting differential behavior in the reactivity in dioxane/water between the (Z)-2,4-dinitrophenylhydrazone (1a) and the (Z)-phenylhydrazone (1b) of 5-amino-3-benzoyl-1,2,4- oxadiazole. The former rearranges into the relevant triazole 2a only at pS+ > 4.5 while undergoing hydrolysis at high proton concentration (pS+ < 3.5); on the contrary, the latter rearranges into 2b in the whole pS+ range examined (0.1 e pS+ e 14.9). Thus, for a deeper understanding of these differences we have now collected kinetic data on the rearrangement in dioxane/water of a series of 3- or 4-substituted (Z)-phenylhydrazones (1c-l) of 5-amino-3-benzoyl-1,2,4-oxadiazole in a wide ra…

Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.

2022

Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with …

Hydrophobic pocket targeting probes for enteroviruses

2015

Visualization and tracking of viruses without compromising their functionality is crucial in order to understand virus targeting to cells and tissues, and to understand the subsequent subcellular steps leading to virus uncoating and replication. Enteroviruses are important human pathogens causing a vast number of acute infections, and are also suggested to contribute to the development of chronic diseases like type I diabetes. Here, we demonstrate a novel method to target site-specifically the hydrophobic pocket of enteroviruses. A probe, a derivative of Pleconaril, was developed and conjugated to various labels that enabled the visualization of enteroviruses under light and electron micros…

Rearrangements of 1,2,4-Oxadiazole: “One Ring to Rule Them All”

2017

[Figure not available: see fulltext.] 1,2,4-Oxadiazoles are heterocycles characterized by low aromaticity and the presence of a weak O–N bond and are widely studied due to their tendency to rearrange into more stable heterocyclic compounds. This review covers literature from the last fifteen years, highlighting the general features of 1,2,4-oxadiazoles and their applications. Regarding the reactivity, the development of classical reactions (thermal and photochemical rearrangements) is presented in terms of synthetic utility and mechanistic insight. Among the relevant rearrangement reactions, the Boulton–Katritzky Rearrangement (BKR), Migration – Nucleophilic Attack – Cyclization (MN…