5-Isoquinolinesulfonamide derivatives. III. Synthesis and vasodilatory activity of 1-(5-isoquinoline-sulfonyl)piperazine derivatives.

On the basis of a hypothesis that cyclization and alkylation of the diamine part in formula 1 may give highly active compounds, a new series of 5-isoquinolinesulfonamide derivatives, shown as formula 2, were prepared from cyclic diamines. Their vasodilatory effects were subsequently evaluated in vivo according to the increase in arterial blood flow after the formulas were injected locally to the femoral and/or vertebral arteries of dogs. Cyclization of the diamine structure in formula 1 gave very potent vasodilators: 6 and 14. Acylation and sulfonylation of terminal amino nitrogen afforded much less potent compounds. In contrast to the hypothesis, alkylation on the ring carbon and the terminal nitrogen of the cyclic amine afforded less active compounds except for compound 11. The most active compounds, 6, 11 and 14, showed more potent vasodilatory effects and more selective activity to the vertebral artery than either trapidil or diltiazem.     

Indole derivatives. I.β-(3-indolyl) ketones

A number of -skatyl--substituted acetoacetic esters (ethyl, tert. -butyl, and benzyl) are prepared by treating gramine with sodium derivatives of -substituted acetoacetic esters. When ethyl -alkyl--skatylacetoacetates are heated with dilute alkali, they are split into indole and a substituted acetoacetic ester, while saponification with concentrated alcoholic alkali gives -substituted-(3-indolyl)propionic acids. 3-Skatyl-heptan-2-one can be obtained by pyrolysis of 3-skatyl-3-carbo-tert. -butoxyheptan-2-one, or by hydrogenolysis of 3-skatyl-3-carbobenzoxyheptan-2-one over a palladium catalyst. Alkylation of cycloheptanone and cyclohexanone enamines by gramine gives cyclic-(3-indolyl)ketones, viz., 2-skatylcyclopentanone and 2-skatylcyclohexanone.     

Tetrazole derivatives. 26. 2-Aryl-3-(p-dimethylaminophenyl)-5-phenyltetrazolium salts

Deeply colored tetrazolium salts were obtained by oxidation of triarylformazans containing a p-dimethylamino group in the N-phenyl substituent with bromine or nitrous acid.See [1] for communication 25.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 987–990, July, 1981.     

Indole derivatives. 131. The basicity of 5- and 6-aminoindoles

The pK_a values for the 5- and 6-aminoindoles were determined from potentiometric titration curves and from ¹³C NMR data on the total change of the chemical shifts of the carbon atom signals on protonation of the amino group. The pK_a values obtained (5.99 and 5.53) were higher than those of aniline (3.92) or -naphthylamine (3.39).For Communication 130, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, 766–769, June, 1988.     

1,6- and 1,7-naphthyridines. I. Rearrangement of quinolinimidoacetic acid derivatives

The reaction of N-substituted quinolinimides 1a-d with sodium alkoxides afforded a mixture of 1,6-naphthyridines 2 and 1,7-naphthyridines 3 which were isolated by chromatographic methods. Structure assignment for each pair of isomers was made by comparison of their ¹H nmr spectra with those of picolinamide and nicotinamide. When esters 1a -c were treated with alkoxides from primary alcohols, other than that of the ester, total transesterification took place. Experimental results suggest that transesterification occurs in open intermediary species.     

Pyrimidine derivatives XII. A convenient preparation of 6-formylpyrimidinedione and 2- and 3-formylpyridine derivatives from corresponding nitrooxymethyl derivatives

The convenient preparation of 6-fomylpyrimidinedione derivatives and 2- and 3-formylpyridine are described. Thus, 5-bromo-1,3-dimethyl- ( 1a ), 5-bromo-3-methyl-1-(2-nitrooxyethyl)- ( 1b ), and 5-bromo-3-methyl-1-(3-nitrooxypropyl)-2,4(1H,3H)-pyrimidine-dione ( 1c ) were converted to the corresponding 6-formyl compounds 2a, 2b , and 2c , respectively, in excellent yields by the reaction with triethylamine and 1,4-diazabicyclo[2.2.2]octane. These 6-formylpyrimidinedione derivatives are key intermediates for the preparation of 6-carbon-carbon substituted compounds, which are expected to be potential antitumor and antiviral agents. Similarly, 2-(and 3-)formylpyridine ( 9a (and 9b )) were obtained by the reaction of 2-(and 3)nitrooxymethylpyridine ( 8a (and 8b )) with 1,4-diazabicyclo[2.2.2]octane.     

Indolizines. 6. Relative reactivities of isomeric 6-, 7-, and 8-ethoxycarbonylindolizine derivatives

The kinetics of the alkaline hydrolysis of 2-phenyl-6-, -7-, and -8-ethoxycarbonylindolizines were studied. The rate constants for the hydrolysis of these compounds and the indexes of the dissociation constants of 2-phenylindolizine-6-,-7-, and -8-carboxylic acids were determined by spectrophotometry. The indexes of the electronic structures and reactivities of 2-methyl-6-, -7-, and -8-ethoxycarbonylindolizines were calculated from theory.See [1] for Communication [5].Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 627–633, May, 1979.     

Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives.

To find a novel alpha-blocker with high alpha-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking selectivity as well as potent alpha-blocking activity.     

Indole derivatives. 136. 4-, 5-, 6-, and 7-Nitro-3-indolesulfonic chlorides and sulfonamides

The reaction of nitroindoles with chlorosulfonic acid in the presence of sodium sulfate was used to synthesize 4-, 5-, 6-, and 7-nitroindole-3-sulfonyl chlorides. Under the influence of ammonia and several amines these compounds were convened to nitroindole-3-sulfonamides which were reduced with hydrazine hydrate in the presence of Raney nickel to the corresponding amines.See [1] for Communication 135.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1341–1345, October, 1990.     

Indole derivatives. 128. Synthesis and properties of 5,6- and 4,5-ethylenedioxyindoles

Reaction of 3,4-ethylenedioxyphenyldiazonium chloride with ethyl 2-methylacetoacetate and subsequent cyclization of the 3,4-ethylenedioxyphenylhydrazone of ethyl pyruvate gives a 14 mixture of 4,5- and 5,6-ethylenedioxy-2-ethoxycarbonylindoles, respectively, from which 4,5- and 5,6-ethylenedioxyindoles are formed by subsequent hydrolysis and decarboxylation. Mannich and Vilsmeyer reactions as well as acetylation and azo coupling have been studied for 5,6-ethylenedioxyindole.For Communication 127, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1624–1628, December, 1986.     

Indole derivatives. 135. 5-[2-(4-Methoxyphenyl)ethenyl]indolines and indoles

5-[2-(4-Methoxyphenyl)ethenyl]indolines were obtained from 5-formyl-1-methyl- or 5-forrayl-1-benzylindolines by the Witting reaction with 4-methoxybenzylidenetriphenylphosphorane. Their dehydrogenation led to the formation of the corresponding compounds of the indole series. The corresponding hydroxy compounds were obtained by demethylation of the methoxyindole with boron tribromide and were converted into the acetoxy derivatives of indoline and indole.For communication 134, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 911–914, July, 1989.     

Nitrogen derivatives of 2-(1-naphthyl) thiopene. II

5-Amino-2-(1-naphthyl) thiophene and 4-amino-2-(1-naphthyl) thiophene are synthesized in the form of their complex salts with stannic chloride. It is shown that the stannic chloride complexes with amino derivatives of 2-(1-naphthyl) thiophene diazotize, and can be used as azo components.For Part I see [1].     

Syntheses of new 1,2-, 1,3-, and 1,4-diazine derivatives. 1. Synthesis of diazinylarylacetonitriles

A number of diazinylarylacetonitriles were obtained in the reactions of properly substituted 3-chloropyridazine, 2-chloropyrimidine, or 2-chloropyrazine derivatives with various arylacetonitriles. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1346–1354, September, 2006.