A large group of 3-methylidene, 5-methylidene, and 3,5-dimethylidene derivatives, as well as pyrrolo-[3,4-b]indole and pyrrolo[3,4-b]quinoline derivatives, has been synthesized on the basis of pyrrolidine-2,4-dione (tetramic acid). Some of the synthesized 3,5-disubstituted pyrrolidine-2,4-diones exhibit anticonvulsant activity.

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The aim of the study is to evaluate the metabolism of progestin drug Gestobutanoil in the experiment with administration of tablet dosage form containing Gestobutanoil (2 mg), to experimental animals (rats and rabbits). Materials and Methods. There was performed analysis of biomatrix obtained from different species of animals: female rats weighing 200.0±60.0 g and female rabbits weighing 3.0±0.2 kg, which were administered different doses of the drug, single or multiple. Metabolites were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). Results. The analysis shows that Gestobutanoil is rapidly metabolized into 17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one (AMP-17) and 17-hydroxy-6-methylpregna-1,4-diene-3,20-dione in the form of acetate (MA). The steroid core of Gestobutanoil has the butyric acid radical in the 3β position. This radical cleavage underlies biotransformation of Gestobutanoil. The obtained pharmacokinetic parameters for metabolites have demonstrated that Gestobutanoil has a stepwise nature of metabolism: the time to reach the maximum concentration of AMP-17 is 1.5 h, MA-3 h. Also AMP-17 proves to penetrate into the peripheral tissues better than MA. Conclusion. The data obtained speak of a unique, different from other gestagens, metabolism of Gestobutanoil. Unlike the known progestogen medroxyprogesterone acetate whose main route of transformation is hydroxylation of the steroid nucleus of the molecule with rather high bioavailability in an unchanged state, Gestobutanoil shows rapid biotransformation into metabolites AMP-17 and MA manifesting their own gestagenic activity with release of butyric acid, which, in turn, may produce a calming effect on the central nervous system.

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Reactions of 3 [(N aryl N chloroacetyl)amino] 2 formylindoles with substituted anilines gave 1,4 diaryl 2 oxo 1,2,3,6 tetrahydro[1,4]diazepino[6,5 b]indol 4 ium chlorides and those with 4 aminopyridine yielded 4 amino 1 (1 aryl 2 oxo 2,5 dihydro 1H pyrido[3,2 b]indol 3 yl)pyridinium chlorides. Reduction of 1,2,3,6 tetrahydrodiazepinoindol 4 ium chlorides af forded the corresponding hexahydro derivatives. An alternative synthesis of 1 (4 nitrophenyl) 3 oxo 4 phenyl 1,2,3,4,5,6 hexahydro[1,4]diazepino[6,5 b]indole from 3 [N (4 nitro phenyl)amino] 2 [(phenylimino)methyl]indole was developed. The method involves the fol lowing sequence of transformations: reduction, chloroacetylation, and intramolecular alky lation.