Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

The corresponding 5(4)-mercaptoimidazoles, from which various 5(4)-mercaptoimidazole-4(5)-carboxylic acid derivatives were synthesized, were obtained from the amide and ethyl ester of 5-diazoimidazole-4-carboxylic acid by substitution of the diazo group. 5-Diazo-imidazole-4-hydroxamic acid does not undergo substitution with sodium disulfide but does undergo cyclization to 3-N-hydroxyimidazo[4,5-d]-1,2,3-triazin-4-one under these conditions. The kinetics of the cyclization of diazoimidazoles were studied, and the interrelationship between the structure and reactivity of the latter was examined.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1550–1554, November, 1975.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 9. peculiarities of the reaction of 5(4)-aminoimidazole-4(5)-carboxhydrazide with nitrous acid and of 5-diazoimidazole-4-carboxazide with amines

The reaction of 5(4)-aminoimidazole-4(5)-carboxhydrazide with nitrous acid was investigated. A mixture of four compounds, viz., 5-diazoimidazole-4-carboxazide, 5-diazoimidazole-4-carboxylic acid, 5(4)-aminoimidazole-4(5)-carboxazide, and 2-azahypoxanthine, is formed under all of the investigated conditions, 5(4)-Azidoimidazole-4(5)-carboxamide derivatives were obtained in the reaction of diazoimidazole-carboxazide with various amines in protic and aprotic solvents. 5-N-(Piperidyl)-azoimidazole-4-carboxazide was isolated only in the reaction with piperidine in an aqueous medium.See [1] for Communication 8.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1536–1540, November, 1980.     

Synthesis and properties of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 14. Acylation of 5(4)-aminoimidazole derivatives

The acylation of 5(4)-aminoimidazole derivatives was studied. It is shown that acylation by means of carboxylic acid anhydrides and chlorides takes place at the amino group, whereas acylation by means of chlorocarbonic acid esters takes place at the nitrogen atoms of the imidazole ring. Methods for the selective introduction of a carbomethoxy group in the 1, 3, and 5 positions of the 5(4)-aminoimidazole-4(5)-carboxamide molecule were developed.See [1] for communication 13.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 247–252, February, 1984.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

5-Diazoimidazole-4-carboxazide was isolated in the diazotization of 5(4)-aminoimidazole-4(5)-carboxhydrazide. The diazotization of N-substituted hydrazides of 5(4)-aminoimidazole-4(5)-carboxylic acis was studied. It is shown that the resulting diazo derivatives undergo cyclization to 3-arylideneaminoimidazo[4,5-d]-1,2,3-triazin-4-ones.See [1] for communication 7.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 984–985, July, 1979.     

Synthesis and properties of analogs of 5 (or 4)-aminoimidazole-4 (or 5)-carboxamide (AICA) and purines. 13. Synthesis of 5 (or 4)-hydrazinoimidazqles and their derivatives

A method for the synthesis of derivatives of 5 (or 4)-hydrazinoimidazole-4 (or 5)-carboxylic acid by reducing the corresponding diazoimidazoles with stannous chloride has been developed, and a number of hydrazones and semicarbazides have been synthesized. It has been shown that under the reduction conditions selected imidazo[4,5-d]-1, 2, 3-triazinone does not have cryptodiazonium properties.For Report 12, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1555, November, 1983.     

Substituted 4(5H)-oxazolones and their salts. 3. Synthesis of 4(5H)-oxazolonium salts from amides of 2,4-dihydroxy-3,3-dimethylbutanoic acid

2-Alkyl-substituted 4(5H)-oxazolonium salts were synthesized by the reaction of amides of 2,4-dihydroxy-3,3-dimethylbutanoic (pantoic) acid with aliphatic carboxylic acid anhydrides in the presence of an equimolar amount of perchloric acid. The hydrolysis of these salts was realized. Various acyl derivatives of pantoic acid amides were obtained, and the possibility of their cyclization to give 4(5H)-oxazolonium salts under the influence of condensing reagents was demonstrated. The mechanism of the heterocyclization of pantoic acid amides is discussed on the basis of these results.See [1] for communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 894–900, July, 1981.     

Synthesis and properties of (4-hydroxy-5-methoxycarbonylthieno)-tetrathiafulvalenes

6-Hydroxy-5-methoxycarbonylthieno[2,3-d]-1,3-dithiol-2-thione, -2-one, and 2-selenone were prepared by intramolecular cyclocondensation of 4-methoxycarbonylmethylthio-1,3-dithiol-2-thione-, 2-one-, and 2-selenone-5-carboxylic acid methyl ester. 2,6(7)-Di(methoxycarbonylmethylthio)-3,7(6)-di(methoxycarbonyl)tetra-thiafulvalene, 2-methoxycarbonylmethylthio-3-methoxycarbonyl-6,7-ethylenedithiotetrathiafulvalene, and the corresponding thieno-condensed tetrafulvalene derivatives were synthesized from them. The electrochemical oxidation potentials of the new tetrafulvalene derivatives were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 761–768, June, 1993.     

Synthesis and Antimicrobial Activity of Quinazolin-4(3H)-ones Incorporating Sulfonamido-4-thiazolidinone

Some new derivatives 7‐chloro‐2‐[2‐(2,6‐dichlorophenyl)amino]benzyl‐3‐[4‐(2‐substituted phenyl‐4‐oxo‐ thiazolidin‐3‐yl)phenyl]sulfonamido‐quinazolin‐4(3H)‐ones 5a – 5l were synthesized from 2‐[2‐(2,6‐dichloro‐phenyl)amino]phenyl acetic acid via acid chloride, benzoxazinone, amino quinazolin‐4(3H)‐one and Schiff base formation. The synthesized compounds were screened for in vitro antibacterial and antifungal activities by broth micro dilution method. Some of the Schiff base as well as 4‐thiazolidinone derivatives showed promising antibacterial activity while pronounced antifungal activity was observed against C. albicans.     

Indole and quinoline derivatives of 2,3-dihydro-l-benzothiepin-4(5H) one

By application of the Friedlander synthesis on 2,3-dihydro-l-benzothiepin-4(5H) one (4), the corresponding [4,5-b]quinoline derivatives 5a and 5b were obtained. Starting from the ketone (4) and by application of the Fischer indole synthesis, 1-benzolhiepino[4,5-b ]indole (6) and 1-benzothiepino[4,5-b]benzo[g]indole (7) were obtained. When β-naphthylhydrazine was used in the indolisation reaction, a mixture of 1-benzothiepino[4,5-b]benzo[e]indole ( 8 ) and 1-benzothiepino[4,3-b]benzo[e] indole (9) was obtained.     

Studies on Reactions of Cyclic Oxalyl Compounds with Hydrazines or Hydrazones. 2. Synthesis and Reactions of 4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid

4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid, obtained from the corresponding furan-2,3-dione and N-benzylidene-N'-(4-nitrophenyl)hydrazine, was converted via reactions of its acid chloride with various alcohols or N-nucleophiles into the corresponding ester or amide derivatives. The nitrile of the starting acid and 1-(4-aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic acid were also obtained. While cyclocondensation reactions of the two acids and the nitrile mentioned with hydrazines lead to pyrazolo[3,4-d]pyridazine derivatives, the reaction of starting acid with 2-hydrazinopyridine provided the hydrazonopyrazole acid derivative.     

Synthesis and microbial screening of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives

The present investigation describe the synthesis of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Quinolin-8-ol was transformed by five step synthetic procedures into 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one. Subsequently, 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one condensed with 1,3-Diphenyl-1H-pyrazole-4-carbothioic acid amide in the presence of acetonitrile to afford 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Synthesized compounds were screened for their antimicrobial activity against gram-positive and gram-negative bacteria. Most of the synthesized compounds are found to be active against tested bacterial strains and fungal strain.     

2-(3-芳氧甲基-4-苯基-1,2,4-三唑-5-硫基)乙酸的微波合成及生物活性研究

在微波辐射条件下, 芳氧乙酰肼经两步反应制得4-苯基-3-芳氧甲基-1,2,4-三唑-5-硫酮衍生物, 再与氯乙酸反应得到6种尚未见文献报道的2-(3-芳氧甲基-4-苯基-1,2,4-三唑-5-硫基)乙酸衍生物. 目标化合物的结构经IR, ¹H NMR和元素分析进行了确证. 生物活性试验结果表明, 该类化合物对双子叶植物油菜具有良好的生物调节活性.     

Synthesis and properties of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 11. Investigation of the structure and reactivity of imidazolethioamides

The IR, UV, and PMR spectra of 5(4)-mercaptoimidazole-4(5)-carboxamide, 5(4)-hydroxyimldazole-4(5)-thiocarboxyamide, 5(4)-mercaptoimidazole-4(5)-thiocarboxamide, and the corresponding methyl derivatives were studied. It is shown that the mercaptoimidazoles obtained exist in the form of zwitterions in solution. The methylation of the mercapto- and hydroxyimidazoles with various methylating agents in solvents was investigated, and the reaction of the thioamides with hydrazine was carried out.See [1] for Communication 10.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 957–962, July, 1982.     

Syntheses of 3-[5-Methyl-1-(4-Methylphenyl)-1,2,3-Triazol-4-yl]-6-Substituted-s-Triazolo[3,4-b]-1,3,4-Thiadiazoles

1,2,3-Triazole derivatives have been reported as inhibiting tumor proliferation, invasion, and metastasis^[1]. The fused l,3,4-triazolo[3,4-b]-1,3,4-thiadiazoles derivatives show various biological effects such as antifungal^[2], antibacterial, hypotensive and CNS depressant activities^[3]. We have reported several 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazoles in the previous paper^[4]. The novel 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[2,4-b]-1,3,4-thiadiazoles 6a-j have been synthesized by the condensation of 4-amino-5-mercapto-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazole 5 with various aromatic carboxylic acids in the presence of phosphorus oxychloride. The mercaptotriazole 5 was prepared from 4,the latter being prepared from 1 throng 2 and 3. The title compounds 6 were depicted in scheme 1. The structures of these compounds were established by elemental analysis, NMR, MS and IR techniques.     

C-alkyl-4-nitropyrazoles from 5-chloro-4-nitropyrazoles

5-Chloro-4-nitro-1H-pyrazoles reacted with arylsulfonyl-, cyano-, and acetylacetic acid esters in DMSO in the presence of potassium carbonate to give 5-[alkoxycarbonyl(acetyl, cyano, or arylsulfonyl)-methyl]-substituted 4-nitropyrazoles which may be promising from the viewpoint of preparation of other functionalized pyrazole derivatives and bicyclic ensembles.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

4-Chloroimidazo[4,5-d]-1,2,3-triazine was obtained by oxidative chlorinatlon from imidazo[4,5-d]-1,2,3-triazine-4-thione, and its reaction with nucleophilic agents and cleavage of the triazine ring to give 5-diazoimidazole-4-carbonitrile were studied. The newly synthesized diazoimidazole was subjected to C- and N-diazo coupling. It was established that 3-methylimidazo[4,5-d]-1,2,3-triazine-4-imine, formed by reaction of the diazo compound with methylamine, is capable of recyclization to 4-methylaminoimidazo[4,5-d]-1,2,3-triazine.See [1] for communication IV.Translated from Khimiya Getereotsiklicheskikh Soedinenii, No. 4, pp. 556–559, April, 1976.     

Preparation of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)-5-methoxybenzo[b]furan derivatives and their leukotriene B(4) inhibitory activity

A series of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)benzo[b]furan derivatives 6-10 were prepared and their leukotriene B(4) inhibitory activity was evaluated. We found that several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors. Among them, 3-(4-chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 9b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252.     

One-step synthesis of substituted 2-amino-5,6,7,8-tetrahydro-4H-benzo[b]pyrans. Molecular and crystal structure of 2-amino-3-(2-methoxyethoxycarbonyl)-4-(2-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran

Substituted 2-aminobenzo[b]pyrans were synthesized by three-component condensation of aromatic aldehydes, cyanoacetic acid derivatives, and cyclic 1,3-diketones. The molecular and crystal structure of 2-amino-3-(2-methoxyethoxycarbonyl)-4-(2-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran was established by X-ray diffraction analysis.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

The Synthesis And Crystal Structure Of 3-[5-Methyl-1-(4-Methylphenyl)-1,2,3-Triazol-4-yl]-s-Triazolo[3,4-b]-1,3,4-Thiadiazole

Likewise the 1,3,4-thiadiazole nucleus which incorporates an N-C-S linkage exhibits a large number of biological activities^[1]. The fused 1,3,4-triazolo[3,4-b]-1,3,4-thiadiazoles derivatives show various biological effects, such as antifungal^[2], antibacterial, hypotensive and CNS depressant activities^[3]. The novel 3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole 6 have been synthesized by the condensation of 4-amino-5-mercapto-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazole 5 with formic acid in the presence of phosphorus oxychloride. The compound 5 was prepared from 4 that was prepared from 1 throng 2 and 3. Recently, we obtained the crystal structure of the novel compound 3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole, C₁₄H₁₂Cl₃N₇S, Mr=416.72, Crystallizes in the triclinic space group with unit cell parameters a=9.049(2), b=10.486(3), c=10.843(2)Å, α=116.79(2), β=93.83(2), γ-100.64(3)°. V=889.3(4)ų, Z=1, Dx-0.778 Mgm^-3. The final R was 0.0535.