The alkylations of Ei-acylamino-l,2,3-thiadiazoles (4) have been investigated ; the N -3 position is preferably alkylated forming new mesoionic heterocycles ( 5 ) and (1 0). The mesoionic 1,2,3-thiadiazolium-5-alkoxyand -5-aryloxy-carbonylaminides are converted into the corresponding salts of the 5-imine derivatives (1 1 ) by hydrolysis with hydrochloric acid.

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BackgroundTaxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy.MethodsFrom January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model.ResultsNinety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P < 0.001). The hazard ratios for the accumulation rate and cumulative dose, evaluated using Cox proportional hazards regression analysis, were 1.44 (P = 0.036) and 0.99 (P < 0.001), respectively.ConclusionsThe results of the present study indicated that the drug accumulation rate influenced the time to onset of docetaxel-induced onychopathy.Trial registrationThis study is not applicable for trial registration due to retrospective chart review without intervention.

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Das Hydrazid (I) wird mit dem Phthalimid (II) zum Hydrazon (III) kondensiert, dieses zum Thiadiazol (IV) cyclisiert, aus dem unter Abspaltung der Schutzgruppe das Amin (V) erhalten wird, das mit Chlorameisenesterzum Acylaminothiadiazol (VIa) kondensiert.