On the reactivity of nitrosoimidazoles with acids (the Cusmano–Ruccia reaction): a continuous source of new ring-into-ring interconversion

An extension of the ‘Cusmano–Ruccia’ reaction is reported. 6-(4-chlorophenyl)-3-methyl-5-nitrosoimidazo[ 2,1-b]oxazole by the action of hydrochloric acid gives 3-(4-chlorobenzoyl)-5-methyl-1,2,4-oxadiazole (13); presumably via ammonium ion, CO2 and methanol elimination. The relevance of the nature of the atom of the B-ring linked to C-2 of the imidazole for the occurrence of the ring-into-ring interconversion has been once more confirmed

Determination of the absolute configuration of the enantiomers of an oxadiazol-3-one calcium channel blocker, resolved by chiral HPLC, via concerted use of three chiroptical spectroscopies

Presentazione orale a Congresso riguardante la possibilita' di determinare la configurazione assoluta di alcune molecole correlabili strutturalmente al diltiaze

ortho-Substituted (aryl)(3-nitrobenzo[b]thiophen-2-yl)amines: study of the electrochemical behavior

The reduction potentials of the title compounds 4 have been measured by cyclic voltammetry. The effect of the substituents has been evaluated by using a linear free energy relationship treatment, thus evidencing that the present ortho-substituents affect the Epc values basically by electronic effects. A comparison with data previously collected on ortho-substituted (aryl)(2-nitrobenzo[b]thiophen-3-yl)amines 3 has provided some interesting information. Different electrochemical behaviors are observed during the reduction (a reversible process and an irreversible process are operating in 3 and 4, respectively): to elucidate the reasons for this different behavior, the "reversible" reduction potentials of 5 and of 6 have been measured. Moreover, higher susceptibility constants have been calculated for compounds of series 4 with respect to those of series 3 (rho4 = 329 and rho3 = 182, respectively). A rationale for all of these findings has been offered

Butadienic Building Blocks from 2-Nitrothiophene as Precursors of Nitrogen Heterocycles: Intriguing Dichotomic Behavior

none9With the goal of their exploitation for the synthesis of heterocycles, sulfides 10 and sulfones 11, derived from the initial ring-opening of 2-nitrothiophene (5) with pyrrolidine/AgNO3 in EtOH, were reacted with diazomethane. Interesting dichotomic behavior was found to yield pyrazolines 17 from 10 and isoxazolines 18 (as the main products) from 11. Intriguingly enough, in the latter case, an unexpected apparent C-C methylene insertion was also observed, leading to the homologous cyclopropanes 19 as secondary products.BIANCHI L.; GIORGI G.; MACCAGNO M.; PETRILLO G.; ROCCA V.; SANCASSAN F.; SCAPOLLA C.; SEVERI E.; TAVANI C.Bianchi, Lara; Giorgi, G.; Maccagno, Massimo; Petrillo, Giovanni; Rocca, VALERIA MARISA; Sancassan, Fernando; Scapolla, Carlo; Severi, E.; Tavani, Cinzi

Preliminary Finding on a New Calcium Channel Entry Blocker Chemotype: 5,6-Diamino-4-hydroxy-2-mercaptopyrimidine Derivatives

We report the preliminary in vitro characterization of a series of pyrimidines as a new chemotype that modulates cardiovascular parameters and relaxes ileum smooth muscle according to classical calcium entry blockers. Tested compounds showed an interesting negative inotropic selectivity. In patch-clamp experiments they block L- over T-type calcium currents. Two requisites seem essential for the activity: lipophilic substituents in positions 2 and 5 of the pyrimidine ring and the acetamidic function in position 6

Synthesis and biological evaluation of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines as new inhibitors of the Wnt/β-catenin signaling

Wnt/β-catenin signaling plays an important role in the regulation of embryonic development and tumorigenesis. Since its deregulation results in severe human diseases, especially cancer, the Wnt signaling pathway constitutes a promising platform for pharmacological targeting of cancer. In this study we synthesized a series of imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyridines and identified some derivatives that were able to inhibit the Wnt/β-catenin signaling pathway in a luciferase reporter assay and cell proliferation in selected cancer cell lines, endowed with APC or β-catenin gene mutations. The most active compounds significantly downregulate the expression of Wnt target genes such as c-myc and cyclin D1. Further studies indicated that these compounds function independently of GSK-3β activity. More importantly, in vivo experiments, carried out on a Wnt-reporter zebrafish model indicate, in particular for compounds 4c and 4i as the most active compounds, an activity comparable to that of the reference compound IWR1, suggesting their potential use not only as small molecule inhibitors of the Wnt/β-catenin signal in Wnt driven cancers, but also in other Wnt-related diseases

Absolute configuration and biological profile of two thiazinooxadiazol-3-ones with L-type calcium channel activity: a study of the structural effects

In the framework of our interest in racemic thiazinooxadiazol-3-ones we determined the absolute configuration and the biological activity as L-type calcium channel blockers of two compounds that differ in the length of the acetal chain, which could affect the pharmacological profile. We observed an interesting inversion of the stereoselectivity, with the activity residing on the R-form for a short chain compound (n = 1) and on the S-form for a long chain one (n = 12). The length of the linear acetal chain appears to be able to invert the stereoselectivity of such a class of compounds, and in silico simulations suggested that this different behaviour might be explained by different hydrophilic and hydrophobic interactions with the binding site