G. Ya. Dubur

Autoxidative transformations of 2-substituted 3-alkyl-4-hydroxy-1-oxo-1, 2-dihydroisoquinolines

A method for the preparation of 2-substituted 3-alkyl-4-hydroxy-1-oxo-1, 2-dihydroisoquinolines is described. It is shown that 2, 3-dialkyl-substituted derivatives readily undergo autoxidation and dealkylation to give N-methylphthalonimide and 3-hydroperoxy and 3-hydroxy-2, 3-dialkyl-1, 4-dioxo-1,2,3,4-tetrahydroisoquinolines.

Preparation and properties of piperidine salts of 6-hydroxy-4,6-diaryl-5-ethoxycarbonyl-3-cyanopiperidine-2-thiones

Alkylation of piperidine salts of 6-hydroxy-4,6-diaryl-5-ethoxycarbonyl-3-cyanopiperidine-2(1H)-thiones yielded 6-hydroxy-2-alkylthio-4,6-diaryl-5-ethoxycarbonyl-3-cyano-3,4,5,6-tetrahydropyridines which were dehydrogenated with the formation of 2-methylthio-1,4- and 4,5-dihydropyridines. The oxidation of the compounds prepared has been studied.

13C-NMR spectra of substituted 1,4-dihydropyridines

It has been found that the electron shift in the C(2)=C(3) bond, under the influence of the substituent attached to the nitrogen atom and the substituents in the 3- and 5-positions, occurs via a π-inductive mechanism. 4-(1,4-Dihydropyridyl) functional groups behave as electron donating substituents via an inductive mechanism.

Synthesis and cardiovascular activity of 4-substituted 2-alkylthio-1,4-dihydropyridines

decrease in pressure was more pronounced. The remaining compounds were inactive under these experimental conditions. In experiments on an isolated seminal duct of rats during intramural electrical irritation of adrenergic nervous extremities, compounds la-c, Va, Vllc at concentrations of i0-6-i0 -~ g/ml did not change the contraction amplitude of the organ, i.e., did not display sympatholytic action. Under these experimental conditions, octadyne decreased the contraction amplitude of an isolated seminal duct by 50% at a concentration of 5.4.10 -7 g/ml.

Octahydropyrrolo[4,3,2-m,n]acridine derivatives. 2. 1-Aryl-4,4,8,8-tetramethyl-2,3,4,5,7,8,9,10-octahydropyrrolo[4,3,2-m,n]-acridin-10-ones and intermediates in their synthesis

A series of 9-aroyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroxanthen-1,8-diones has been prepared from arylglyoxals and dimedone in a dehydrating medium; upon heating with ammonia these compounds are converted to 1-aryl-4,4,8,8-tetramethyl-2,3,4,5,7,8,9,10-octahydropyrrolo[4,3,2-m,n]acridin-10-ones. These reactions occur via the intermediate formation of tetrahydroindole derivatives.

Synthesis of 3-amino-6-methyl-5-ethoxycarbonyl-4,7-dihydrothieno(2,3-b)pyridine derivatives

The alkylation of piperidinium salts of substituted 1,4-dihydropyridine-2-thiols with chloroacetonitrile or iodoacetamide gave 2-cyanomethylthio- and 2-carbamoylmethylthio-substituted 6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-3-cyano-1,4-dihydropyridines, which undergo intramolecular cyclization in basic media to give 3-amino-6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-2-cyano(carbamoyl)-4,7-dihydrothieno[2,3-b]pyridines.

Synthesis of 3-cyano-4, 6-diaryl-3, 4-dihydropyridine-2-thionks

Abstract3-Cyano-4, 6-diaryl-3, 4-dihydropyridine-2-thiones have been synthesized for the first time by the condensation of arylideneacetophenones or 1-piperidino-1-phenyl-2-benzoylethane with cyanothioacetamide and the 1, 1-dicyano-2-aryl-3-benzoylpropane with hydrogen sulfide in the presence of bases. It has been established by PMR spectroscopy that 3-cyano-3,4-dihydropyridine-2-thiones exist in solutions in the form of mixture of cis and trans isomers.

Effects of glutapyrone, a new amino acid-containing 1,4-dihydropyridine, on focal penicillin-induced epileptic activity and on bicuculline- or thiosemicarbazide-induced convulsions

1. A. A. Bonetskii and V. I. Fedorov, Lab. Delo, No 4, 2125 (1989). 2. A. A. Bonetskii and V. I. Fedorov, Fiziol. Zh. SSSR, 76, No 4, 486-491 (1990). 3. A. A. Bonetskii and V. I. Fedorov, Pat. Fiziot., No. 3, 10-12 (1992). 4. V. V. Karpitskii, S. V. Slovesnov, and R. A. Rerikh, Ibid., N o . 1, 74-77 (1986). 5. G. Feuerstein, P. Boonyaviroj, and Y. Gutman, Eur. Z Pharmacol., 44, 131-142 (1977). 6. A. F. Junod, Amer. Rev. Resp. Dis., 115, N_~ 6, 51-57 (1977). 7. N. Katon, D. D. Sheriff, C. Siu, and K. S~awa, Amer. J. Physiol., 256, No 1, Pt. 2, H291-H296 (1989). 8. D. Palaic and P. A. KhairaUah, J J)harm. PharmacoL, 19, 396-397 (1967). 9. J. M. Patel, F. R. Yarid, E. R. Block, and M. K. Raizada, Amer. J. Physiol., 256, No 5, Pt. 1, C987-C993 (1989). 10. A. B. Silverberg, S. D. Shan, M. W. Haymond, and P. E. Oryer, Ibid., 234, No 3, E252-E256 (1978).

Bromination of 4-aryl-3,5-dialkoxycarbonyl-2,6-dimethyl-1,4-dihydropyridines

Abstract4-Aryl-3,5-dialkoxycarbonyl-2,6-dimethyl-1,4-dihydropyridines are brominated by N-bromosuccinimide in methanol at room temperature at the methyl groups at positions 2 and 6 to form mono-, di-, tri-, and tetrabromo derivatives. When the N-unsubstituted bromomethyl-1,4-dihydropyridines are heated they are easily converted to tetrahydrofuropyridines, but in the case of the analogous N-substituted-1,4-dihydropyridines cyclization does not occur. The 2,6-bis(bromomethyl)-substituted products easily replace bromine under the influence of nucleophilic reagents.

Synthesis, antioxidant activity and membrane binding of 4,5,6-substituted 2-methylthio-3-cyano-1,4-dihydropyridines

Continuing our research on the synthesis and properties of the 2-alkylthio-l,4-dihydropyridines [1, 2], we have obtained new 4,5,6-substituted 2-methylthio-3-cyano-1,4-dihydropyridines, and determined their antioxidant activity (AOA) and membrane binding level. AOA has been extensively studied in the 2,6-dimethyl-3,5-dialkoxycarbonyl-l,4-dihydropyridine series [3, 4]. Antioxidant and hepatoprotective properties have also been found in related compounds such as the 1,4-dihydropyridine-2(3H)thiones [5, 6, 7]. Investigation into the AOA and membranotropic properties of the newly-synthesized 2-alkylthio-l,4dihydropyridines is vital in the continuing search for physiologically active substances among the derivatives of 1,4dihydropyridines (DHP), since the peroxide oxidation of lipids and the regulation of this process by membranotropic compounds is of considerable importance in a number of diseases. 4,5,6-Substituted 2-methylthio-3-cyano-l,4-DHP (Ia, lb, Id-g) were obtained in high yields by alkylating readily available piperidine 3-cyano-l,4-dihydropyridine-2-thiolate with methyl iodide or dimethyl sulfate. Compound Ic was synthesized either by alkylating 1,4-dihydropyridine-2(3H)-thione, or dehydrating the appropriate 6-hydroxy-l,4,5,6-tetrahydropyridine.