N. S. Minasyan

Synthesis and Neurotropic Activity of 8-Amino Derivatives of Condensed Thieno[3,2-d]- and Furo[3,2-d]Pyrimidines

New derivatives of pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines based on 3-chloro derivatives of pyrano[3,4-c]pyridines and pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines based on previously prepared 8-chloro derivatives were synthesized. Studies of the biological activity of the synthesized compounds showed that several of them exhibited neurotropic properties.

Synthesis and Neurotropic Activity of Triazolo[3,4-a]-and Triazolo[5,1-a][2,7]Naphthyridines

Methods for synthesizing new substituted 7,8,9,10-tetrahydro[1,2,4]triazolo[3,4-a][2,7]naphthyridines from -hydrazino-7-isopropyl-3-chloro-5,6,7,8-tetrahydro[2,7]naphthyridine-4-carbonitrile were developed. It was shown that heating triazolo[3,4-a][2,7]-naphthyridines in an excess of amines produced isomeric triazolo[5,1-a][2,7]naphthyridine derivatives. These isomers were interconverted using a Dimroth rearrangement. The neurotropic activity of the synthesized compounds was studied.

Annulation of 6-aminouracils with 2,3-dimethoxy- and 2-fluorobenzaldehydes and 2-chloro-7-methoxyquinoline-3-carbaldehyde

Abstract6-R-Aminouracils reacted with 2,3-dimethoxybenzaldehyde to give 10-R-substituted 9-methoxy-5-deazaflavins. No expected 5-deazaflavins were obtained in analogous reactions of 2,3-dimethoxybenzaldehyde with 6-aminouracil hydrochlorides. On the other hand, the corresponding 5-deazaflavin and naphthyridine hydrochlorides were formed in the reactions of 6-aminouracil hydrochlorides with 2-fluorobenzaldehyde and 2-chloro-7-methoxyquinoline-3-carbaldehyde. The newly synthesized 9,10-substituted 5-deazaflavins and benzo[b]pyrimido[5,4-g][1,8]naphthyridines attract interest as potential biologically active substances and substrates for further structural modifications.

Synthesis and neurotropic activity of 6,8-diamino derivatives of pyrano[3,4-c]pyridines

New diamino derivatives of pyrano[3,4-c]pyridines were synthesized by the pyridine ring recyclization. The presence of the intramolecular hydrogen bond in 6-[(4-methoxyphenyl)amino]-3,3-dimethyl8-methylamino-3,4-dihydro-1H-pyrano[3,4-c]pyridin-5-carbonitrile was identified by X-ray diffraction. A pharmacological study of the synthesized compounds was carried out in known tests, such as assay for antagonism induced by corazole subcutaneous injection and the open field test. The method of rotating rod was used to evaluate neurotoxicity. The diamino derivatives of pyrano[3,4-c]pyridines were found to possess neutrotropic properties. The synthesized compounds, as well as diazepam, prevent the occurrence of clonic seizures and clonic corazoleinduced convulsions in animals; however, they cause a behavior-depressing sedative effect.

Functionalization of 5-(4-alkoxybenzyl)-4-R-4H-1,2,4-triazole-3-thiols. Synthesis of novel DNA methylation inhibitors

Aminomethylation and cyanoethylation reactions of 5-(4-alkoxybenzyl)-4-methyl(phenyl, allyl)-4H-1,2,4-triazole-3-thiols have been investigated. According to NMR spectroscopy data, the reactions occur at the nitrogen atom Ν2. The effect of the synthesized compounds on cancer DNA methylation has been evaluated.

Synthesis of (Piperidin-1-yl)trihydropyrano(cyclopenta)- (4',5')pyrido(3',2' : 4,5)thieno(3,2-e)(1,2,4)triazolo- (4,3-c(1,5-c))pyrimidines

Reactions of 3-cyanopyridine-2(1H)-thiones with ethyl chloroacetate and chloroacetamide gave the corresponding amino-substituted thieno[2,3-b]pyridines which were treated with formamide or ethyl formate to obtain fused pyridothieno[3,2-d]pyrimidinones. The latter were converted into hydrazino derivatives whose cyclocondensation with triethyl orthoformate or formic acid afforded 7,10-dihydro-8H-pyranopyridothienopyrimidines and 2,3-dihydro-1H-cyclopentapyridothienopyrimidines annulated by triazole ring at the pyrimidine ring.

Azido–tetrazole tautomerism of pyrano[3,4- c ]pyridine derivatives

Treatment of N-aryl-8-hydrazinylpyrano[3,4-c]pyridine-5-carbonitriles with sodium nitrite in acetic acid afforded the corresponding 8-azido derivatives existing in solution as equilibrium mixtures with cyclic tetrazole tautomer whose fraction attains 48%. Lower solvent polarity and elevated temperature favor increased fraction of the azido tautomer.

Synthesis and neurotropic activity of the derivatives of fused triazolo[4,3-c]- and triazolo[1,5-c]pyrimidines

The methods for preparation of fused triazolo[4,3-c]- and triazolo[1,5-c]pyrimidines were developed. The Dimroth rearrangement of these systems was studied. Pharmacological investigation of the synthesized compounds was conducted in known tests, such as antagonism with subcutaneous administration of corazole and the open-field test. The rotating rod method was used to assess the neurotoxicity. Neurotropic properties were found in many derivatives of triazolopyrimidine. They, like diazepam, prevent the occurrence of clonic twitching and corazole-induced clonic convulsions in animals. All selected compounds as well as diazepam exhibit an anxiolytic effect.

Synthesis of 5,8-Diamino-Substituted Pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and Pyrimido[4′,5′:4,5]thieno[2,3-c]isoquinolines

Ethyl 1-amino-8,8-dimethyl-5-(piperidin-1-yl)-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate and ethyl 1-amino-5-(piperidin-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxylate reacted with benzoyl isothiocyanate to give the corresponding 1-thioureido derivatives which underwent cyclization to 2,2-dimethyl-5-(piperidin-1-yl)-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one and 5-(piperidin-1-yl)-10-thioxo-1,2,3,4,10,11-hexahydropyrimido-[4′,5′:4,5]thieno[2,3-c]isoquinolin-8(9H)-one. The cyclization products were converted into 8-chloro derivatives, and the chlorine atom therein was replaced by various amines.

New derivatives of 1,3,4-thiadiazole based on hydrazide of 3-methoxyphenoxyacetic acid

Abstract2-Substituted 1,3,4-thiadiazole-5-thiol has been synthesized basing on hydrazide of 3-methoxy-phenoxyacetic acid. Methods of SH-alkylation, aminomethylation, and cyanoethylation of the product have been elaborated. Reactions of the starting hydrazide leading to 4-amino-3,5-substituted 4Н-1,2,4-triazoles and acyl hydrazides of dicarboxylic acids containing pharmacophore groups in the molecule have been studied.