Search results for "Diazole"

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…

Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.

2018

Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)a and IFN? and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activit…

Salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole, a structural and analog of acetazolamide, show interesting carbonic anhydrase inhibitory properties…

2015

Three salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole (Hats) were prepared and characterized by physico-chemical methods. The p-toluensulfonate, the methylsulfonate, and the chlorhydrate monohydrate salts of Hats were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) and as anticonvulsants and diuretics, since many CAIs are clinically used as pharmacological agents. The three Hats salts exhibited diuretic and anticonvulsant activities with little neurotoxicity. The human (h) isoforms hCA I, II, IV, VII, IX, and XII were inhibited in their micromolar range by these salts, whereas pathogenic beta and gamma CAs showed similar, weak inhibitory profiles.

Zn2+ and Cu2+ complexes of a fluorescent scorpiand-type oxadiazole azamacrocyclic ligand: crystal structures, solution studies and optical properties

2020

A ligand comprised of a macrocyclic pyridinophane core having a pendant arm containing a secondary amine group linked through a methylene spacer to a pyridyl–oxadiazole–phenyl (PyPD) fluorescent system has been prepared (L). The crystal structures of [ZnL](ClO4)2 and [CuL](ClO4)2 show that M2+ is coordinated to all the nitrogen atoms of the macrocyclic core, the secondary amine of the pendant arm and the nitrogen atom of the pyridine group of the fluorescent moiety, the latter bond being clearly weaker than the one with the pyridine of the macrocycle. Solution studies showed the formation of a highly stable Cu2+ complex with 1 : 1 stoichiometry, whereas with Zn2+ least stable complexes were…

DNA binding and biological activity of Cu(II) and Zn(II) complexes of a 2,5-diphenyl[1,3,4]oxadiazole macrocycle ligand.

2011

Synthesis of Amino-1,2,4-triazoles by Reductive ANRORC Rearrangements of 1,2,4-Oxadiazoles

2010

The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has been investigated. 3-Amino- 1,2,4-triazoles are produced through a reductive ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole followed by ring-opening, ring-closure, and final reduction of the 3-hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4-oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked electron-withdrawing groups.

OXADIAZOLE DERIVATIVES FOR THE TREATMENT OF GENETIC DISEASES DUE TO NONSENSE MUTATIONS

2018

Are disclosed oxadiazole derivatives, their use as medicaments and in particular for the treatment of diseases associated with the presence of a nonsense mutation in the gene or a premature stop codon in the mRNA, pharmaceutical formulation comprising said oxadiazole derivatives and prodrug or mixture thereof and the methods for the preparation of said Oxadiazole derivatives.

Recent Advances in the Chemistry of 1,2,4-Oxadiazoles

2015

1,2,4-Oxadiazoles experienced an almost 80-year long period of scientific lethargy before they tickled the curiosity of chemists. The study of chemical and photochemical reactivity of 1,2,4-oxadiazoles opened the way to a series of applications in heterocyclic synthesis. Today, 1,2,4-oxadiazoles are known in medicinal chemistry for their use as bioisosters of esters and amides. Furthermore, fluorinated 1,2,4-oxadiazoles have been applied in materials science either by themselves or for the targeted modification of polymers and macromolecules. Overall, the synthesis of 1,2,4-oxadiazoles can be planned to fine-tune their properties for featured applications. Their versatility, either as start…

1,2,4-OSSADIAZOLI: UTILI SCAFFOLD NEL DESIGN DI NUOVI FARMACI

2021

DESIGN OF SF3B1 SUBUNIT MODULATORS OF THE SF3B SPLICEOSOME COMPLEX

2022

The subject of this dissertation is the search for new therapeutic strategies for pancreatic cancer and aims to implement a Drug Discovery process for the rational design and synthesis of molecules active in the modulation of pathways related to the regulation of pre-mRNA splicing process. This research project is the result of a joint PhD between the University of Palermo, Italy, and the Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. It integrates complementary skills in pharmaceutical chemistry and translational cancer research with a special focus on the rational design of new anticancer compounds potentially active on SF3B1 (Splicing Factor 3B …