Synthesis of new fluorinated low molecular weight (LMW) gelators

Study of Reactivity in the 1,3-Dipolar Cycloaddition Reactions Leading to New Triazolopyrrolopyrazine Ring Systems

The influence of the structural symmetry of the 2-pi double-reactive-sites component in the 1,3-dipolar cycloaddition reactions, involving nitrilimines as dipoles, was investigated. the experimental data showed that the loss of the symmetry leads to the formation of the monocycloadduct in good yields.

In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents

Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum , Leishmania infantum , Trypanosoma brucei , and Trypanosoma cruzi , resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds

Synthesis of Isoxazoline Derivatives through Boulton–Katritzky Rearrangement of 1,2,4-Oxadiazoles

The base-induced rearrangement of 1,2,4-oxadiazoles into isoxazoline derivatives is reported. This represents the first example of a three-atom side-chain rearrangement that involves a saturated CCO side chain at C-3 of the oxadiazole. Nonaromatic 3-amino-isoxazoline derivatives are obtained in good yields. Interestingly, this reaction occurs through the rearrangement of aromatic oxadiazoles to form less stable bonds than those that are broken.

Sintesi di nuovi low molecular weight (LMW) hydrogelators fluorurati

New triazolo-pyrrolopyrazine systems by 1,3-dipolar cycloaddition

A convenient synthesis of cycloadduct bis-1,2,4-triazolo[4,3-a:3’,4’-c]quinoxalines by 1,3-dipolar cycloaddition

Reattività di diazine benzocondensate asimmetriche nelle reazioni di cicloaddizione 1,3-dipolare con dipoli nitriliminici

Bis-1,2,4-triazolo[4,3-a:3′,4′-c]quinoxalines of pharmaceutical interest from 1,3-dipolar cycloaddition

Abstract Various derivatives of the heterocyclic system 1,12,12a,12b-tetrahydrobis-1,2,4-triazolo[4,3-a:3′,4′-c]quinoxaline of pharmaceutical interest have been obtained by double site- and regio-selective 1,3-dipolar cycloaddition of arylnitrilimines to quinoxalines. No evidence for the formation of mono-adducts was obtained, at variance with literature reports. Specific studies to establish the exact stereochemistry of the bis-cycloadducts were undertaken.

New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding…

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole ligands

Abstract The synthesis and structural characterization of Ni II , Cu II and Zn II complexes of two chelating 1,2,4-oxadiazole ligands, namely 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA) 2 (H 2 O) 2 ](ClO 4 ) 2 and [M(pyOXA) 2 (ClO 4 ) 2 ], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1 H and 13 C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possib…

Synthesis, characterization, cellular uptake and interaction with native DNA of a bis(pyridyl)-1,2,4-oxadiazole copper(II) complex

The copper(II) complex of 3,5-bis(2'-pyridyl)-1,2,4-oxadiazole was synthesized and characterized. X-Ray crystallography revealed that the complex consists of a discrete [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) cation and two ClO(4)(-) anions. The Cu(II) coordination sphere has a distorted octahedral geometry and each ligand chelates the copper ion through the N(4) nitrogen of the oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water molecules are in cis position and each of them is H-bonded to the 5-pyridyl nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion. Biological assays showed that, despite the free ligand not being …

Sintesi e valutazione biologica di 1,2,4-ossadiazoli analoghi del Linezolid

Synthesis of isoxazoline derivatives by Boulton-Katritzky Rearrangements

Synthesis of fluorinated oxadiazoles with gelation and oxygen storage ability

A new family of fluorinated low molecular weight (LMW) gelators has been synthesized through SNAr substitution of 5-polyfluoroaryl-3-perfluoroheptyl-1,2,4-oxadiazoles with glycine ester. The obtained compounds give thermal and pH-sensitive hydrogels or thermo-reversible organogels in DMSO. Oxygen solubility studies showed the ability to maintain high oxygen levels in solution and in gel blend with plate counter agar (PCA).

Synthesis of Isoxazoline Derivatives through Boulton-Katritzky Rearrangement of 1,2,4-Oxadiazoles

The base-induced rearrangement of 1,2,4-oxadiazoles into isoxazoline derivatives is reported. This represents the first example of a three-atom side-chain rearrangement that involves a saturated CCO side chain at C-3 of the oxadiazole. Nonaromatic 3-amino-isoxazoline derivatives are obtained in good yields. Interestingly, this reaction occurs through the rearrangement of aromatic oxadiazoles to form less stable bonds than those that are broken.

Sintesi di nuovi bent-core LC fluorurati

Sintesi di derivati triazolo-chinossalinici e triazolo-pirrolopirazinici di interesse farmaceutico mediante cicloaddizioni 1,3-dipolari

ChemInform Abstract: Synthesis of Isoxazoline Derivatives Through Boulton-Katritzky Rearrangement of 1,2,4-Oxadiazoles.

This is the first report of the rearrangement of 1,2,4-oxadiazole with saturated C—C—O side chains and an unusual example of an irreversible rearrangement that allows the formation of nonaromatic heterocycles.

Sistemi pirrolo/indolo-pirazinici anellati di interesse farmaceutico. progettazione e sintesi mediante cicloaddizioni 1,3-dipolari.

New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5- yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4- oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistan…

Reactivity of asymmetric benzo-condensed diazines with nitrilimine dipoles in the 1,3-dipolar cycloaddition reactions

The reactivity of asymmetric benzo-condensed diazines in the 1,3-dipolar cycloaddition reactions with nitrilimines was investigated. The results demonstrated that, at variance with the symmetric quinoxaline, a certain grade of diastereoselectivity emerged. Moreover in the case of the 5-methylquinoxaline and quinazoline a mono-cycloadduct was obtained.

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(20-pyridyl)-1,2,4-oxadiazole and 3-(20-pyridyl)5-(phenyl)-1,2,4-oxadiazole ligands

The synthesis and structural characterization of NiII, CuII and ZnII complexes of two chelating 1,2, 4-oxadiazole ligands, namely 3,5-bis(20-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(20-pyridyl)5- (phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA)2(H2O)2](ClO4)2 and [M(pyOXA)2(ClO4)2], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1H and 13C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possible consequence of the format…

Synthesis and biological evaluation of 1,4-oxadiazole analogues of Linezolid

Sintesi di ossadiazoli fluorurati come nuovi Low molecular weight hydrogelators

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

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.

Sintesi di Low Molecular Weight Gelators (LMWG) Fluorurati

In vitro and in silico studies of polycondensed diazine systems as anti-infective agents

Infective diseases caused by protozoarian agents are still relevant today more than ever. In fact, they represent the first cause of death all over the world with seventeen millions victims every year. The development of drug resistance and the broad diffusion of these pathologies make actual the research of new molecules able to act as selective and effective anti-infective chemotherapics.[1] Recently several polycondensed diazine derivatives, by means 1,3-dipolar cycloaddition, reactions [2, 3] were synthesized. A broad selection of these compounds chosen with a wide pattern of substitutions were submitted to biological in vitro screening against Plasmodium falciparum, Leishmania Infantum…

1,3-Dipolar cycloadditions in the synthesis of annelated diazines: design of new scaffolds for anticancer and antimicrobial agents

Sintesi di 1,2,4-ossadiazoli fluorurati analoghi del Linezolid come potenziali anti-batterici

L'aumentata multidrug resistance tra i batteri patogeni Gram-positivi ha riacceso l'interesse verso la ricerca di nuove classi strutturali di antibiotici attivi nei confronti di batteri multiresistenti.1 Il Linezolid, appartenente alla classe degli ossazolidinoni, è il capostipite di una nuova generazione di anti-batterici di sintesi attivi contro patogeni Gram-positivi.2 La ricerca di nuovi analoghi del Linezolid risulta quanto mai attuale dato il recente riscontro di fenomeni di resistenza batterica a tale farmaco.3 In questo contesto, verranno presentati alcuni risultati preliminari relativi allo sviluppo di nuove metodologie di sintesi per l’ottenimento di composti eterociclici fluorura…

Bioactive compounds containing benzoxadiazole, benzothiadiazole, benzotriazole.

New triazolopyrrolopyrazine and triazoloindolopyrazine systems of biological interest by 1,3-dipolar cycloaddition

Novel ANRORC rearrangements of 1,2,4-oxadiazoles

Sintesi di derivati tetraidrobis-triazolochinossalinici e di nuovi sistemi triazolopirrolopirazinici di interesse biologico mediante cicloaddizioni 1,3-dipolari

Bis-1,2,4-triazolo[4,3-a:3’,4’-c]quinoxalines of pharmaceutical interest from 1,3-dipolar cycloaddition

ChemInform Abstract: Synthesis of Amino-1,2,4-triazoles by Reductive ANRORC Rearrangements of 1,2,4-Oxadiazoles.

The hydrazinolysis of the oxadiazoles under optimized conditions allows a general synthesis of functionalized aminotriazole products which are of interest due to the biological activity of the heterocyclic system.

Synthesis and preliminary antibacterial evaluation of Linezolid-like 1,2,4-oxadiazole derivatives

In the present study the synthesis of new Linezolid-like molecules has been achieved by substitution of the oxazolidinone central heterocyclic moiety with a 1,2,4-oxadiazole ring. Two series of 1,2,4-oxadiazoles, bearing different side-chains and containing a varying number of fluorine atoms, were synthesized and preliminarily tested for biological activity against some Gram-positive and Gram-negative bacteria using Linezolid and Ceftriaxone as reference drugs