Synthesis and biological activities of new 1,4-benzothiazine derivatives.

New 2H-1,4-benzothiazin-3(4H)-one derivatives possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position were synthesized and tested for calcium antagonistic and calmodulin antagonistic activities. Antihypertensive effects in spontaneously hypertensive rats were also evaluated. In general, these compounds were rather weak calcium channel blockers, although, in contrast, many of them had moderate to potent calmodulin antagonistic activity, and 2-[3-(4-(4-fluorophenyl)-1-piperazinyl]propyl]-2H-1,4-benzothiazin -3 (4H)-one derivatives 45, 74 and 75 showed potent antihypertensive effects.     

Synthesis and oxidation of 2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylic acid esters

Twenty-six esters of 2,6-dihydropyridine-3,5-dicarboxylic acid were obtained by means of the Hantzsch pyridine synthesis. The synthesized compounds were oxidized by chloranil to the corresponding pyridine derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1230–1237, September, 1975.     

Synthesis and biological activities of new 2-substituted 1,4-benzoxazine derivatives.

A series of new 1,4-benzoxazine derivatives (XI, XII) possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position and related compounds (XIII) were synthesized and tested for calcium antagonistic, calmodulin antagonistic and antihypertensive activities. Various compounds had in vitro calmodulin antagonistic activity superior or comparable to that of trifluoperazine. Among these compounds, tetrahydronaphtho[2,3-b] [1,4]oxazine derivatives such as 51, 53, 54, 58, 59, 60, 73 and 75 showed potent antihypertensive effects in spontaneously hypertensive rats. Optical isomers of 51 were also synthesized and evaluated biologically. No differences in biological activities were seen between the enantiomers.     

Synthesis of Ammonium 5-Arylcarbamoyl-4-heteryl-6-methyl-3-cyano-1,4-dihydropyridine-2-thiolates and 4-Heteryl-5-carbamoyl-6-methyl-3-cyano-1,4-dihydropyridine-2-selenolates

The condensation of enamines derived from acetoacetanilides, heterocyclic aldehydes, and cyanothioacetamide yielded ammonium 5-arylcarbamoyl-5-heteryl-6-methyl-3-cyano-1,4-dihydropyridine-2-thiolates, which were subsequently used for the synthesis of substituted 2-alkylthio-1,4-dihydropyridines, 2-alkylthiopyridines, and thieno[2,3-b]pyridines. The reaction of acetoacetamide with heteroaromatic aldehydes and cyanoselenoacetamide in the presence of N-ethylmorpholine yielded N-ethylmorpholinium 4-heteryl-5-carbamoyl-6-methyl-3-cyano-1,4-dihydrolyridine-2-selenolates, from which substituted 2-alkylseleno-1,4-dihydropyridines were prepared.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 483–492.Original Russian Text Copyright © 2005 by Dyachenko.     

Synthesis and antitumor activities of novel 1,4-substituted phthalazine derivatives

<正>A series of 1,4-substituted phthalazine derivatives were designed and synthesized.All the prepared compounds were screened for their cytotoxic activities against A549.HT-29 and MDA-MB-231 cell lines in vitro.Among them,compounds 7a-7h showed excellent selectivity for MDA-MB-231 cell line with IC_(50) values from 1 nmol/L to 0.92μmol/L.A preliminary SAR study of these derivatives was performed.     

Studies on chemotherapeutics I. Synthesis of 5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylic acid derivatives

Ethyl 5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylates were synthetized by reacting 1,3,5-triazine with 4-substituted ethyl acetoacetate derivatives in ethanol, in the presence of sodium ethoxide. The l-alkyl-5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylic acids required for the antimicrobial studies were prepared by N-alkylation (with triethyl phosphate or alkyl halides) and alkaline hydrolysis of the pyridone esters.     

Bromination of amides of 2,6-dimethyl-1,4-dihydropyridine-5-carboxylic acids

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, p. 1276, September, 1991.     

Synthesis and Electrochemical Oxidation of Nitriles of 4-Aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic Acids

Nitriles of 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-6-hydroxy-1,4,5,6-tetrahydropyridine-3-carboxylic acids were obtained by the alkylation of 1,4,5,6-tetrahydropyridine-2-thiolate with iodoacetamide or by a three-component synthesis by condensing 2-arylmethylene-1,3-dicarbonyl compounds with 2-cyanothioacetamide in the presence of piperidine with subsequent reaction with iodoacetamide. Nitriles of 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acids were obtained by the dehydration of 6-hydroxy-1,4,5,6-tetrahydropyridines or with a one-reactor three-component system from 2-cyano-3-(4-methoxyphenyl)thioacrylamide, 1,3-dicarbonyl compounds, and iodoacetamide. The electrochemical oxidation of the synthesized nitriles was investigated and it was established that derivatives of 1,4,5,6-tetrahydropyridine as a rule are oxidized readily to the corresponding 1,4-dihydropyridines. A comparative analysis has been carried out of the ability of hydrogenated pyridines to be oxidized electrochemically depending on the electron-withdrawing properties of the substituents in the heterocycle.     

Bromination of amides of 2,6-dimethyl-1,4-dihydropyridine-5-carboxylic acids

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, p. 1275, September, 1991.     

Synthesis and properties of derivatives of 1,4-dihydropyrimidine-5-carboxylic acid

1,4-Dihydropyrimidines were synthesized by reductive dethionation of the corresponding 2-thiono-4-aryl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid derivatives, and some of their properties were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1223–1227, September, 1986.     

Synthesis of monosubstituted amides of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid

Monosubstituted amides of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid were obtained when acetoacetic acid anilide and 2-pyridylamide were used in place of acetoacetic ester in the Hantzsch synthesis.     

Thiazolo[4,3-c][1,4]benzodiazepines. I. Synthesis of amidine derivatives

Reactivity of 1,2,3,10,11,11a-hexahydro-5H-thiazolo[4,3-c][1,4]benzodiazepin-5-one-11-thione and 1,2,3,10,11,11a-hexahydro-5H-thiazolo[4,3-c][1,4]benzodiazepine-5,11-dithione was evaluated against various amines. The synthetic pathways involved in these reactions which led to new thiazolo[4,3-c]-[1,4]benzodiazepine amidines are described.     

New synthetic method for functionally substituted morpholinium 1,4-dihydropyridine-2-thiolates and their derivatives

By condensation of aromatic aldehydes with cyanothioacetamide and enamines of 1,3-dicarbonyl compounds functionally substituted morpholinium 1,4-dihydropyridine-2-thiolates were obtained applied to the synthesis of 2-alkylsulfanyl-1,4-dihydropyridines, 1,4-dihydrothieno[2,3-b]-pyridines, and 2,3,4,7-tetrahydrothiazolo[3,2-a]pyridine.