217 research outputs found
Investigation of the reaction between 3-benzisothiazolones, an isoindole isoster and activated acetylenes: synthesis of novel heterocyclic backbones for building bioactive molecules
No full textInvestigation of the reaction between benzo[d]isothiazol-3-one, 2-aminobenzo[d]isothiazol-3-one, its isoster 2-aminoisoindolin-1-one, and activated acetylenes, in the presence of triphenylphosphine, led us to synthesize novel heterocyclic compounds that could be attractive for the building of biologically active molecules. A one-pot PPh3-promoted tandem reaction, with acetylene dicarboxylates and dibenzoylacetylene, afforded new tricyclic pyrazolo-fused benzisothiazoles. The PPh3-promoted reaction between benzisothiazolones and methyl propiolate afforded 1,4-benzothiazepine-5-one derivatives, via an isothiazole ring expansion. These studies are providing additional insights in benzisothiazolone chemistry and describe simple and original synthetic accesses to novel derivatives
Computer-Aided Design of Novel Antagonists of the EphA2 Receptor
No full textThe Eph receptors are a large family of receptor tyrosine kinases, and their activity and downstream signaling ability are stimulated by the binding of cell membrane ligands known as ephrins [1]. A growing body of evidence suggests that the pharmacological modulation of the Eph-ephrin system may lead to innovative therapies for the treatment of solid tumors and neurodegenerative disorders [2]. However, the conclusive validation of Eph receptors as a drug targets is hampered by the lack of pharmacological tools featured by PD and PK profiles suitable for in vivo administration.
The discovery of small molecules able to disrupt the Eph-ephrin interaction is a challenging task, due to the large size of the protein interacting surfaces and the lack of specialized chemical libraries to be used in HTS campaigns. Despite these shortcomings, we recently identified lithocholic acid (LCA) as a micromolar antagonist of the EphA2 receptor by means of an ELISA-based screening [2]. In the present talk, the results of our medicinal chemistry efforts devoted to the PD-optimization of LCA will be presented [3,4]. Details of the computational strategies applied to guide the synthesis of novel compounds will be discussed along with an analysis of the structure-activity relationships
La fotomodellazione per il rilievo archeoastronomico
No full textLa fotomodellazione è una nuova tecnologia che consente di creare modelli metrici 3D a partire da semplici fotografie digitali. Caricando nel software di fotomodellazione un adeguato numero di immagini è possibile ottenere in modo automatico, senza che l’operatore debba fare interventi selettivi, la posizione spaziale di tutti i pixel degli “n” fotogrammi scattati dell’oggetto. Il risultato è la generazione di nuvole di punti tridimensionali simili a quelle dei laser scanner. Dalla nuvola di punti è possibile passare alla mesh e al modello completo con texture ortorettificata esportabile in molti formati digitali. Teoricamente, non mancano infatti problematicità, il risultato finale è medesimo a quello di un rilievo effettuato con il laser scanner, ma l’economicità degli strumenti di rilievo (una semplice macchina digitale con una definizione possibilmente superiore ai 5000 pixel) rendono questa tecnologia estremamente innovativa e interessante. L’obiettivo del lavoro, condotto su beni d’interesse archeoastronomico, è di analizzare la logica di questi processi, applicando anche programmi open source sviluppati da enti di ricerca nazionali e internazionali, per verificarne l’applicabilità
4-Chloro-N-(4-chlorophenylsulfonyl)-N-(3-oxo-2,3-dihydro-1,2-benzisothiazol-2-yl)benzenesulfonamide
No full textIn the title compound, C19H12Cl2N2O5S3, the benzene rings of the chlorophenylsulfonyl groups form a dihedral angle of 35.85 (8)° and are inclined at angles of 23.51 (6) and 59.22 (6)° with respect to the essentially planar benzisothiazole ring system [maximum deviation = 0.030 (2) Å]. The molecular conformation is stabilized by an intramolecular C—H...O hydrogen bond. In the crystal packing, molecules are linked into chains parallel to the a axis by intermolecular C—H...O hydrogen bonds and π–π stacking interactions, with centroid–centroid distances of 3.592 (5) Å
4-Methyl-N-(3-oxo-2,3-dihydro-1,2-benzisothiazol-2-yl)benzenesulfonamide
No full textIn the title molecule, C14H12N2O3S2, the benzisothiazolone ring system is essentially planar and forms a dihedral angle of 67.37 (6)° with the plane of the benzene ring. In the crystal structure, molecules are linked via intermolecular N—H...O and C—H...O hydrogen bonds to form chains parallel to the b axis
Complete 1H and 13C NMR spectral assignment of benzo[d]isothiazole derivatives and of an isoindole isoster
No full textSynthesis and antimicrobial properties of 2-(benzylidene -amino)-benzo[d]isothiazol-3-ones
No full textThe in vitro antimicrobial activity of 2-amino-benzo[d]isothiazol-3-one and of several 2-arylideneamino derivatives carrying in the second position a substituted or unsubstituted aromatic ring or an arylalkenylidene moiety was determined by the broth dilution method against several strains selected to define their spectrum and potency. All the compounds demonstrated good antibacterial properties against Bacillus subtilis, streptococci, enterococci and staphylococci including penicillin-resistant clinical isolates. Several compounds showed excellent inhibitory properties against Streptococcus pyogenes, which is the most sensitive microorganism tested. Many benzisothiazolones exhibited good activity against Gram-negative Haemophilus influenzae. As regards antifungal activity, several of the tested compounds inhibited Saccharomyces cerevisiae at concentrations of 3–6 microg ml–1. In all cases the parent 2-amino-benzo[d]isothiazol-3-one was the most effective agent, with minimum inhibitory concentration (MIC) values ranging from 0.07 to 6 microg ml–1. The results obtained indicate that most of these compounds are wide-spectrum antimicrobial substances and promising agents against penicillin-resistant staphylococci
Are we using the right pharmacological tools to target EphA4?
No full textThe EphA4 receptor has been proposed to be a key actor in neurodegenerative diseases. In the last years, several research groups focused their efforts on the discovery of small molecules capable of blocking EphA4 activity by binding its extracellular domain. However, none of the compounds so far identified possess adequate chemical and/or pharmacological profiles to assess the "druggability" of EphA4 in animal models. New efforts are required to deliver a new generation of suitable pharmacological tools
A one-pot PPh3-promoted synthesis of new functionalized heterocycles derived from 2-aminobenzo[d]isothiazol-3-one
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