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Orale Antidiabetica vom Sulfonylsemicarbazid-Typ wie Tolazamid (1) und Glisoxepid (2) wurden unter milden nitrosierenden Bedingungen, auch annahernd physiologischen in vitro Bedingungen, nach einem neuartigen Reaktionsverlauf in Sulfonyltriazene 3a, b umgewandelt. Modellverbindungen mit N4-Acyl-semicarbazidstruktur 4 zeigen abweichendes Reaktionsverhalten, wobei Saureamide 5 neben Nitrosaminen 6 gebildet werden. Nitrosations with Hydrazine Derivatives, VI: Novel Reaction of Oral Antidiabetics of the Sulfonylsemicarbazide Type under Nitrosating Conditions Oral antidiabetics of the sulfonylsemicarbazide type like Tolazamide (1) and Glisoxepide (2) were transformed under mild nitrosating conditions, even nearly physiological in vitro conditions, to sulfonyl triazenes 3a, b by a novel reaction pathway. Model compounds with N4-Acyl-semicarbazide structure 4 showed different reaction behaviour yielding carbonamides 5 and nitrosamines 6.

The effect of some insulinotrophic drugs on the transport of sugar was investigated in fasted, narcotized rats by continuous perfusion of cannulated long intestinal loops with galactose solution (18 mM.) circulated by air lift. Three consecutive perfusions (fifty minutes each) were performed in each rat, the drug being given in the second perfusion only. The rate of galactose disappearance was expressed as per cent of that in the first perfusion in the same rat. Tolbutamide (50 mg./l kg. weight), glycodiazine (50 mg./l kg. weight), glisoxepid (BAY 4231, 2 mg./l kg. weight) and glibenclamide (0.25 mg./l kg. weight) were found to increase the rate of galactose disappearance in the second perfusion by 21 per cent, 5 per cent, 12 per cent and 25 per cent, respectively, and in the third perfusion by 21 per cent, 26 per cent, 32 per cent and 21 per cent, respectively, as compared to the rate in the corresponding perfusion of a control group. This increase was significant (P values < 0.05) with all drugs in the second and third perfusions with the exception of glisoxepid in the second perfusion. These results are discussed in relation to the action of insulin and the effect of diabetes on intestinal absorption of sugars.

Typical signs and symptoms of type III allergy occurred in a 55-year-old diabetic during diabetes and diuretic treatment with glisoxepid, glibenclamide, furosemide and probenecid. Symptoms of this type of allergy unintentionally recurred with every subsequent therapeutic administration of each one of these drugs. The possibility of a cross allergy between sulphonamide diuretics, chemotherapeutic sulphonamides and sulphonyl-urea compounds has only rarely been described.

5-Alkyl-2-(arylsulfonylamino)pyrimidine (1–5 und 11–16) wurden mikrobiologisch hydroxyliert. Mit Streptomyces griseolus wurden Propyl-, Butyl- und lsobutylgruppen an C-2, athylgruppen an C-1, Isopropylgruppen an C-1 und C-2, sowie Neopentylgruppen an C-3 hydroxyliert. Die Antidiabetika Glibenclamid (25) und Glisoxepid (29) mit Sulfonylharnstoff-Struktur wurden zu Sulfonamiden abgebaut, ferner wurden in 2- und 4-Stellung des Cyclohexanrings von 25 Hydroxylgruppen eingefuhrt. Microbiological Transformations of Nonsteroidal Structures, III. Hydroxylation of 5-Alkyl-2-(benzenesulfonylamino)pyrimidines and Structurally Related Antidiabetics 5-Alkyl-2-(arylsulfonylamino)pyrimidines (1–5 and 11–16) have been hydroxylated microbiologically Propyl, butyl, and isobutyl groups were hydroxylated at C-2, ethyl groups at C-1, isopropyl groups at C-1 and C-2, and neopentyl groups at C-3, respectively, by Streptomyces griseolus. The sulfonylurea part of the antidiabetics glibenclamid (25) and glisoxepid (29) was degradated to sulfonamide; in addition, hydroxyl groups were introduced into the 2- and 4-positions of the cyclohexane ring of 25.

1. A modification of the digitonin method of Zuurendonk & Tager (1974) (Biochim. Biophys. Acta 333, 393-399) (i.e. the ‘convaentional’ method) was developed that allows the fractionation of isolated hepatocytes at −5 degrees C (i.e. ‘low-temperature’ method). 2. With respect to compartmentation of adenine nucleotides, glutamate and citrate, the two methods yielded very similar results. 3. In contrast, the mitochondrial amounts of aspartate and malate, as revealed by the low-temperature method, were about twice as high as those found by the conventional procedure. No change in the total cellular content occurred. 4. With n-butylmalonate and glisoxepid present in the conventional digitonin medium, significantly higher amounts of malate and aspartate respectively were found in the mitochondrial pellets. The results obtained by the low-temperature method, however, were not influenced by the these inhibitors. 5. It is concluded that under the conventional conditions of cell fractionation no appreciable redistribution of adenine nucleotides, glutamate and citrate occurs.