Formamidines with antinociceptive and antiinflammatory activities

Pursuing our investigations on 7-amino-2,3-polymethyleneindole derivatives, a set of 7-(dimethylaminomethylene)-amino-2,3-polymethyleneindoles, together with some other aryl or cycloalkyl substituted formamidines, were prepared and tested for analgesic and antiinflammatory activities. Several compounds resulted endowed with one or both of these activities; the indole derivatives 1 and 2 exhibited a good degree of both of them

Amides and formamidines with antinociceptive activity: note II

Forty amides, formamidines and trifluoromethylsulfonylamides bearing on the nitrogen a cyclohexyl residue, eventually 2-substituted, were prepared and tested for analgesic activity against a chemical stimulus. Good activity was exhibited by amides 9, 11 and 28, by formamidine 34, as well as by triflyamide 40. Eleven additional compounds exhibited a moderate activity

Fungicidal activity of some o-nitrophenyl-hydrazones

The antimycotic activity of 16 o-nitrophenylhydrazones against strains of Hansenula anomala, Saccharomyces cerevisiae, Candida parapsyliosis, and Cryptococcus albidus was tested. All 16 compounds inhibited growth of the yeast strains. The inhibitory activity of the 4 methyl-derivatives substituted on the aromatic nucleus was particularly significant

Tricyclic pyrazoles: synthesis and biological evaluation of novel 4,5-dihydrobenzo-1h-6-oxa-cyclohepta[1,2-c] pyrazole-based analogues of the cannabinoid antagonist ness 0327

We report in this poster the synthesis and in vitro evaluation of novel 4,5- dihydrobenzo-1H-6-oxa-cyclohepta[1,2-c]pyrazoles 1Cb-l variously substituted in position 3

Nuovi derivati 1,2-difenil-imidazolici come potenti ed efficaci modulatori allosterici positivi del recettore GABA_A

Il complesso recettoriale GABAA è il più importante recettore inibitorio presente nel sistema nervoso centrale dei vertebrati. Il legame dell’acido γ-aminobutirrico (GABA) ai recettori GABAA induce l’apertura di un intrinseco canale al Cl- con conseguente iperpolarizzazione e inibizione della cellula. Recentemente presso i nostri laboratori abbiamo sviluppato una serie di 1,2-difenilimidazol-piperazine dotate di significativa affinità di legame per i recettori dopaminergici D2- simili, serotoninergici 5-HT1A e 5-HT2A. La nostra attenzione si è focalizzata sulla capacità di alcuni derivati di inibire in modo concentrazione-dipendente (0.1-300 µM) le correnti al Cl- evocate dal GABA su recettori GABAA umani espressi in oociti di Xenopus

Synthesis of amides with anti-inflammatory and analgesic activities

A series of N-Aroyl-cyclohexyl- and cyclohexenylamides 3- or 4-methylsubstituted were synthesized and evaluated for their anti-inflammatory and analgesic potencies, and gastrointestinal irritation liability. One compound, N-benzoyl-4-methyl-cyclohexylamide 6a, possessed an anti-inflammatory activity comparable to that of indomethacin

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Sensitization to methyl methacrylate in the plastic catheter of an insulin pump infusion set

Cases of allergic contact dermatitis due to acrylics in the adhesive used to attach the needle to the tubing have previously been reported in pump infusion set users, but never previously due to an acrylic in the plastic tubing itself, as in this case. The presence of methyl methacrylate demonstrated in the catheter of the patient’s own infusion set correlated with her positive patch test results. Since patch testing and chemical-physical analysis was negative for methyl methacrylate in the alternative Cliniset® microinfusion set, this was supplied to the patient for her insulin therapy and no further adverse skin reactions were reported. Patch testing demonstrated probable cross-sensitivity between methyl methacrylate and other acrylics

Synthesis and cytotoxicity of substituted 2-benzylnaphth[2,3-<i>d</i>]imidazoles

Designed as a new series of so called “bivalent ligand” containing the proposed 2-benzylnaphthimidazole-type structure, a number of 2-benzylnaphth[2,3-d]imidazoles, bearing various substituents, have been prepared by a synthetic approach involving an heterocyclization of 2,3-diaminonaphthalene 4 with appropriate imidates 3 (for 1b–i) followed by alkylation (for 1j–l) with the desired alkylating agent. Compounds 1b–f, h–l were subjected to primary biological evaluation for cancer cell growth inhibition (one-dose, three-cell assay), and the four most active terms, 1c, h, i and j, were then evaluated for their cytotoxic profiles in the National Cancer Institute’s (NCI) human disease-oriented, 60 cell line, in vitro antitumor screening protocol. Among them, two compounds (1h and 1i) are the most representatives demonstrating not only high growth-inhibitory activities against some leukemia cancer cells, but also fairly good activities against the growth of certain cell lines of some solid tumor