Synthesis and anticancer activity evaluation of 3-(4-oxo-2-thioxothiazolidin-5-yl)-1H-indole-carboxylic acids derivatives

Abstract

A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano[3,4-b]indole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of 3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.     

Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones

By cycloaddition of arylazides to acetylacetone are obtained derivatives of 1,2,3-triazole. In the reaction of 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones (VIIa-VIIe) with isatin are obtained 2-[1-(R-phenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-quinolinecarboxylic acids (IIIa–IIIe) and 2-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] -4-quinolinecarboxylic acids (IXa, IXb), respectively. We found that 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) readily transform into [5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] acetic acids (IVa–IVc) by the method of Wilgerodt-Kindler. The (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)acetic acid reacts with 5-phenyl-4-amino-4H-1,2,4-triazol-3-thiol affording 6-[(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl) methyl]-3-phenyl[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazole (VI). Original Russian Text ? N.T. Pokhodylo, R.D. Savka, V.S. Matiichuk, N.D. Obushak, 2009, published in Zhurnal Obshchei Khimii, 2009, vol. 79, no. 2, pp. 320–325.     

From Levulinic Acid to Biheterocycles: Synthesis of 1-[(5-Hydroxy-5-trifluoromethyl-3-substituted-4,5-dihydro-1H-pyrazol-1-yl)-3-(5-trifluoromethyl-1H-pyrazol-3-yl)propan-1-ones

We develop an efficient method to synthesize novel propionyl-spaced bisheterocyclic compounds. It entails cyclocondensation of 3-(5-trifluoromethyl-1H-pyrazol-3-yl)propanoyl hydrazide obtained from levulinic acid, with 1,1,1-trifluoro-4-methoxy-3-alken-2-ones proceeding regiospecifically to 1-[(5-trifluoromethyl-5-hydroxy-3-substituted-4,5-dihydro-1H-pyrazol-1-yl)-3-(5-trifluoromethyl-1H-pyrazol-3-yl)propan-1-one derivatives.     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

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.     

Synthesis and characterization of polymeric triphenyltin and cyclotetrameric tricyclohexyltin 2-(1H-imidazol-1-yl)acetates

The reaction of 2-(1H-imidazol-1-yl)acetic acid with (Ph₃Sn)₂O or Cy₃SnOH (Cy?=?cyclohexyl) yields triphenyltin 2-(1H-imidazol-1-yl)acetate (1) and tricyclohexyltin 2-(1H-imidazol-1-yl)acetate (2), respectively. 2-(1H-imidazol-1-yl)acetates in these two complexes show remarkably different coordination modes. Complex 1 forms a polymeric chain structure through intermolecular Sn–N interactions, while 2 displays a 28-membered macrocyclic tetranuclear structure by the assembly of Sn–N coordination bonds.     

Reactions of 3-alkylsulfanyl-2-arylazo-3-(1-azacycloalk-1-yl)acrylonitriles with maleimide

Reactions of 2-arylazo-3-(1-azacycloalk-1-yl)-3-methylsulfanylacrylonitriles with male-imide in benzene gave octahydropyrrolo[3,4-a]pyrrolizines 2a–c, decahydro-2,7a-diaza-cyclopenta[a]indene 2e, and decahydro-5-oxa-2,7a-diazacyclopenta[a]indene 2f as a result of 1,3-dipolar cycloaddition. In a similar reaction with 3-allylsulfanyl-2-arylazo-3-(1-azacycloalk-1-yl)acrylonitriles 3, dipolar cycloaddition and intramolecular cyclization competed to give a mixture of compounds 2 (major products) and 1,4,6,7,8,8a-hexahydropyrrolo[2,1-c]-1,2,4-triazines 4b–d, 1,6,7,8,9,9a-hexahydro-4H-pyrido[2,1-c]-1,2,4-triazine 4e, and 1,4,6,7,9,9a-hexahydro-1,4-oxazino[3,4-c]-1,2,4-triazine 4f (minor products).     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Novel one-pot multicomponent synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives

Abstract

An expeditious, one-pot multicomponent reaction has been developed for the synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives. Condensation of 4-amino-5-hydrazino-4H-1,2,4-triazole-3-thiol with phthalic anhydride and aromatic aldehyde afforded the (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-diones in acetic acid medium with excellent yields. All the synthesized compounds were characterized by their analytical and spectral data.     

Synthesis and insecticidal activities of O,O-dialkyl-2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyloxy] (aryl) methylphosphonates

A series of novel O,O-Dialkyl-2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyloxy](aryl) methy-lphosphonates I-1–14 were designed and synthesized. The structures of all the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, ³¹P-NMR, IR and elemental analysis. Their insecticidal activities against Mythimna separata and Plutella xylostella were evaluated. The results of bioassays indicated that the title compounds exhibited 20–80% larvicidal activity against Mythimna separata at 1000 mg/L.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

Efficient Synthesis of 6-(1H-1,2,4-Triazol-1-yl)-thieno[2,3-d]pyrimidin-4(3H)-ones via an Iminophosphorane

Ethyl 2-amino-4-methyl-5-(1H-1,2,4-triazol-1-yl)thiophene-3-carboxylate 2, obtained from Gewald reaction of 1-(1H-1,2,4-triazol-1-yl)acetone 1 with ethyl cyanoacetate and sulfur, was transferred into iminophosphorane 3. Further reaction of 3 with aromatic isocyanates gave carbodiimides 4, which were treated subsequently with a secondary amine to give 6-(1H-1,2,4-triazol-1-yl)-thieno[2,3-d]pyrimidin-4(3H)-ones 6 in good yields in the presence of a catalytic amount of sodium ethoxide.     

超声辐射下合成1-[(未)取代苯酰基-3-[5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑-2-基]-硫脲

1-苯基-3-甲基-5-氯吡唑-4-甲酸与氨基硫脲在三氯氧磷中反应得到2-氨基-5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑(1), 然后分别采用超声辐射法和常规加热法与(未)取代苯甲酰基异硫氰酸酯(2)反应合成了一系列未见报到的1-[(未)取代苯酰基-3-[5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑-2-基]-硫脲(3a～3j). 化合物的结构经元素分析, IR, ¹H NMR确证.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesis and mass spectral studies of 1-[5-chloro-1-substituted-2(1H)-pyrazin-2-on-3-yl]-5-aryl-3-methylpyrazoles

Sixteen new 1-[5-chloro-1-substituted-2(1H)-pyrazin-2-on-3-yl]-5-aryl-3-methylpyrazoles V have been synthesized by condensation of 5-chloro-1-substituted-3-hydrazino-2(1H)-pyrazin-2-ones III and 1-aryl-1,3-butanediones IV in dry 1,4-dioxane. The general mass spectral fragmentation mode of these compounds has been studied.     

Synthesis of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles

A number of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles were obtained in high yields by thermal dehydration of acylated 4-methyl-1,2,5-oxadiazole-3-carboxamide hydrazones.     

2-(1-苯基/取代苯基-3-甲基-5-氯-1H-4-吡唑基)-3-芳酰胺-4-噻唑啉酮的合成及生物活性

利用1-芳基-3-甲基-5-氯-1H-4-吡唑醛(2)分别与取代苯甲酰肼反应, 进一步与巯基乙酸关环, 合成了11个新的2-(1-芳基-3-甲基-5-氯-1H-4-吡唑基)-3-芳酰胺-4-噻唑啉酮类化合物 3a～3k, 并利用元素分析, IR, ¹H NMR和X-ray晶体衍射确定了其结构. 初步生物活性表明: 3e具有杀菌活性, 3e和3k具有除草活性.     

Synthesis and characterization of diorganotin(IV) complexes of tridentate Schiff bases: crystal structure of [N-(3-hydroxypyridine-2-yl)-5-chlorosalicylideneiminato]dimethyltin(IV)

Some five-coordinated dimethyltin(IV) complexes of the type Me₂SnL (where L is the anion of a bifunctional tridentate Schiff base) were synthesized. These Schiff bases are N-(3-hydroxypyridine-2-yl)-3-methoxysalicylideneimine, HOC₆H₃OCH₃CH=NC₅H₃NOH (1), N-(3-hydroxypyridine-2-yl)-3-ethoxysalicylideneimine, HOC₆H₃OC₂H₅CH=NC₅H₃NOH (2), N-(3-hydroxypyridine-2-yl)-5-chlorosalicylideneimine, HOC₆H₃ClCH=NC₅H₃NOH (3), and N-(3-hydroxypyridine-2-yl)-3-methoxy-5-bromosalicylideneimine, HOC₆H₂OCH₃BrCH=NC₅H₃NOH (4). Dimethyltin(IV) complex of 3 (3a) was characterized by single crystal X-ray diffraction method and a coordination geometry that is nearly halfway between trigonal–bipyramidal and square pyramidal arrangement was found. Dimethyltin complexes of (1), (2), and (4) were also prepared and characterized by the comparison of their elemental analysis and ¹H-NMR-, IR-, UV- and mass spectral data with those of (3a). For example, in the ¹H-NMR spectra, the ²J(¹¹⁹Sn-¹H) in the Sn-CH₃ moiety have values between 80 Hz and 90 Hz, typical of five-coordinated tin species. By using these values in Lockart’s Equations, H₃C–Sn–CH₃ angles in the complexes were estimated to lie between 130° and 145°. X-ray diffraction value for 3a, confirms this estimate within 3.4% relative deviation (129.7° exp. Vs. 134.9° estimate).     

Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

Synthese von 3,3-Bis(alkylthio)-2-(2-thioxo-benzo-2H-1,3-thiazol-3-yl)-acrylsäure-Derivaten und Kristallstruktur des entsprechenden Ethyl 3,3-Bis(methylthio)acrylats

Summary The 3,3-bis(alkylthio)-2-(2-thioxo-benzo-2H-1,3-thiazole-3-yl)acrylonitriles3a–e, the methyl and ethyl acrylates4 and5a–d, respectively, are prepared by dithiocarboxylation of the corresponding derivatives of acetic acid1a–c. The crystal structure of ethyl 3,3-bis(methylthio)-2-(2-thioxo-benzo-2H-1,3-thiazole-3-yl)acrylate5a has been determined by X-ray analysis.