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Abstract: Chiral racemic α-diimines, tested in aziridination reactions with NsONHCO2Et, for the first time led to the synthesis of (±)-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-α-diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino process. The structures of the compounds were determined using 2D NMR on purified bidiaziridines. [Copyright &y& Elsevier]

Abstract: Introduction: Hyperthyroidism is a relative uncommon but important cause of atrial fibrillation. The aim of this study was to investigate the utility of routine thyroid-stimulating hormone (TSH) determination in the emergency department (ED) in patients presenting to the ED with stable, new-onset atrial fibrillation. We derive a set of clinical criteria in which TSH is likely to be normal and therefore thyroid function evaluation deferrable to a different time from ED visit. Methods: Cross-sectional observational study in a university hospital. Thyroid-stimulating hormone was measured in all patients admitted to the ED observational unit for new-onset atrial fibrillation in a 30 consecutive months'' period. Patients'' clinical characteristics and treatment received in the ED were recorded. Recursive partitioning analysis technique was used to determine which predictors were associated with a TSH level less than 0.35 μIU/mL. Results: Of 433 patients enrolled, 47 (10.8%) had a low TSH. Thyroid-stimulating hormone highly correlated with FT3 and FT4 levels (P < .001) confirming its good predictive value as screening tool. Recursive partitioning analysis showed that previous thyroid disease (P < .01), stroke/transient ischemic attack (P < .01), and hypertension (P = .10) were associated with low TSH. The final model had sensitivity of 93% and specificity of 31%, corresponding to a negative likelihood ratio of 0.02 (0.01-0.07). Conclusion: Hyperthyroidism is present in nearly 10% of new-onset atrial fibrillation. Although thyroid function screening is recommended in all patients, a simple model that included previous thyroid disease, stroke, and hypertension might help to identify those patients at high risk (low TSH) in the ED. [Copyright &y& Elsevier]

Abstract: (E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent. Similar results were obtained in the epoxidation reactions performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral diaziridines or oxaziridines were obtained with very high enantiopurity. [Copyright &y& Elsevier]

Abstract: New heterocyclic compounds characterized by the presence of a diaziridine and an oxaziridine ring directly bound were reported. A first desymmetrization reaction of α-diimines using nosyloxycarbamate as aminating agent in a H2O/CH2Cl2 system gives (E)-3-(iminomethyl)diaziridine-1-carboxylates which were further functionalized obtaining the never synthesized before 3-(diaziridin-3-yl)oxaziridines. [Copyright &y& Elsevier]

6,7-Dimethoxytetrahydroisoquinoline is widely used as basic moiety in σ 2 receptor ligands, in order to provide σ 2 versus σ 1 selectivity. This same moiety is also widely exploited in modulators of P-glycoprotein (P-gp) efflux pump, so that mixed σ 2 /P-gp agents are often obtained. Deconstruction of 6,7-dimethoxytetrahydroisoquinoline moiety present in the potent mixed σ 2 /P-gp agent 6,7-dimethoxy-2-[4-[1-(4-fluorophenyl)-1 H -indol-3-yl]butyl]-1,2,3,4-tetrahydroisoquinoline ( 1 ) could lead to the separation of σ 2 affinity from P-gp activity. Therefore, phenethylamino-, benzylamino- and indanamine series were obtained. The NH group was also methylated in the N-phenethylamino series, and ethylated in the benzylamino series, to better match 6,7-dimethoxytetrahydroisoquinoline. The σ 2 affinity drastically decreased with the increase of conformational freedom, whereas alkylation of the NH-group was beneficial for σ 2 receptor interaction. By contrast, deconstruction of 6,7-dimethoxytetrahydroisoquinoline slightly reduced P-gp activity, with dimethoxy-substituted derivatives displaying potent P-gp interaction. Therefore, ‘ring-opened’ 6,7-dimethoxytetrahydroisoquinoline derivatives represent a promising strategy to obtain P-gp selective agents devoid of σ 2 receptor affinity. [ABSTRACT FROM AUTHOR]