Synthesis and anti-inflammatory-analgesic activity of 2'',4''-difluoro-3-(carbamoyl)biphenyl-4-yl benzoates

Eighteen 2',4'-difluoro-3-(carbamoyl)biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1H NMR, MS and elemental analysis. The anti-inflammatory activity and analgesic activity for 18 compounds were evaluated. The preliminary assay results showed that compounds 4a and 4p exhibited potent anti-inflammatory-analgesic activity.     

Synthesis and anti-inflammatory-analgesic activity of 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates

Eighteen 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1^H NMR, MS and elemental analysis. The anti-inflammatory activity and analgesic activity for 18 compounds were evaluated. The preliminary assay results showed that compounds 4a and 4p exhibited potent anti-inflammatory-analgesic activity.     

Synthesis and pharmacological evaluation of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles: A condensed bridgehead nitrogen heterocyclic system

A series of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a–j and 5a–d) were synthesized by condensation of 4-amino-5-diphenylmethyl-4H-1,2,4-triazole-3-thiol with various substituted aromatic acids and aryl/alkyl-isothiocyanates. The structures of synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectroscopic studies. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic, lipid peroxidation and hepatotoxic effects. Compounds 6-(4-chlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (4a) and 6-(2,4-dichlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole(4c) emerged as the most active compounds of the series and were moderately more potent than the standard drug ibuprofen.     

Synthesis of {2,3-Dihydro-7-halopyrrolo-[(2,1-b)]-quinazolin-9-(1H)-one and 2,3-Dihydro-5,7-dihalopyrrolo-[(2,1-b)]-quinazolin-9-(1H)-one}: New Analogs of Deoxyvasicinone

A series of novel halogen-substituted deoxyvasicinone {2,3-dihydro-7-halopyrrolo-[(2,1-b)]-quinazolin-9-(1H)-one and 2,3-dihydro-5,7-dihalopyrrolo-[(2,1-b)]-quinazolin-9-(1H)-one} derivatives was synthesized by condensation of halogenated anthranilic acids (2, 3, 4, 5) with 4-aminobutyric acid (6) in refluxing m-xylene over phosphorus pentoxide for 3 h to give the desired compounds (7a–7d).     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Synthesis and antimicrobial activities of some novel substituted 2-imidazolyl-N-(4-oxo-quinazolin-3(4H)-yl)-acetamides

Several substituted-quinazolin-3(4H)-ones 8-11ad were synthesized by condensation of 2-chloro-N-(4-oxo-substituted-quinazolin-3(4H)-yl)-acetamides with various substituted imidazoles through one pot reaction. Elemental analysis, IR, (1)H-NMR and mass spectral data confirmed the structure of the newly synthesized compounds. Synthesized quinazolin-4-one derivatives were investigated for their antitubercular, antibacterial and antifungal activities. Some of the tested compounds showed good antitubercular activity. None of the synthesized compounds showed significant antibacterial and antifungal activity.     

Enantiomeric separation of novel anticancer agent 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one

The enantiomers of 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one, a novel anticancer agent, were separated by derivatisation with caronaldehyde, separation of the resulting diastereoisomers of the corresponding esters by silica gel column chromatography and regeneration of alcohols (S)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one under aqueous conditions. The absolute configuration of the enantiomers was determined by 1H NMR studies of the corresponding Mosher esters. Alternatively, the enantiomers were separated by preparative HPLC to collect the (S)- and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-ones with high purity which was comparable with that obtained by the chemical method. The details of these methods have been presented herein.     

Synthesis,anti-inflammatory and analgesic activity of 2-[4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid derivatives

The title compounds 3a–l have been synthesized by the reaction of thiocarbohydrazide with substituted phenoxy acetic acid to obtained substituted 1,2,4-triazoles (1). Compound 1 was treated with various substituted aromatic aldehydes which results in 4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-2H-1,2,4-triazol-3(4H)-thiones (2a–g), further 2a–g is converted to 2-[4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3a–l) derivatives by the reaction with chloroacetic acid. All the newly synthesized compounds were evaluated for in vivo anti-inflammatory and analgesic activities. Among the series 2-[4-(2,4-dichlorobenzylideneamino)-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3d), 2-[4-(4-dichlorobenzylideneamino)-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3e), 2-[4-(2,4-dichlorobenzylideneamino)-5-[(2,4-dichlorophenoxy)methyl]-4H-1,2,4-triazol-3-yl thio] acetic acid (3j) and 2-[5-[(2,4-dichlorophenoxy)methyl)]-4-(4-chlorobenzylideneamino)-4H-1,2,4-triazol-3-yl thio] acetic acid (3k) showed significant anti-inflammatory activity with P < 0.001 (63.4%, 62.0%, 64.1% and 62.5% edema inhibition, respectively), as compared to the standard drug diclofenac (67.0%) after third hour respectively and also compounds 3j, 3k exhibited significant analgesic activity with P < 0.001 (55.9% and 54.9% protection, respectively) and less ulcerogenic activity as compared with standard drug aspirin (57.8%).     

Synthesis and anticonvulsant activity of some quinazolin-4-(3H)-one derivatives

A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity.     

One-pot multi-component synthesis of novel ethyl-2-(3-((2-(4-(4-aryl)thiazol-2-yl)hydrazono)methyl)-4-hydroxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate derivatives and evaluation of their in vitro antimicrobial activity

A novel series of ethyl-2-(3-((2-(4-(4-aryl)thiazol-2-yl)hydrazono)methyl)-4-hydroxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate derivatives ( 4a-f and 5a-f ) were synthesized by employing one-pot multi-component approach involving ethyl 2-(3-formyl-4-oxy/isobutoxyphenyl)-4-methylthiazole-5-carboxylate, thiosemicarbazide and various phenacyl bromides/3-(2-bromoacetyl)-2H-chromen-2-one/2-(2-bromoacetyl)-3H-benzo[f]chromen-3-onein ethanol in the presence of catalytic amount of acetic acid. The structures of all the synthesized compounds were confirmed with spectral analysis, ie, IR, 1H NMR, 13C NMR and mass spectrometry, and all the compounds were screened for their in vitro antimicrobial activity.     

Synthesis, characterization, and biological activities of some transition metal(II) complexes with the thiosemicarbazone derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one

A new 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one thiosemicarbazone (HL) was synthesized derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one. Four transition metal(II) complexes of HL have been prepared. Elemental analysis, molar conductivity, IR, UV, ¹H NMR spectra, and TG-DTA have been used to characterize these complexes. The complexes have the general formula ML₂, where M = Zn, Cu, Co, and Ni. The ligand and its complexes have been studied for their possible biological activity including anti-inflammatory, antibacterial, and antitumour activity in vitro.     

Synthesis,Bioactivity and Crystal Structure Analysis of 2-(Benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) Acetamide

A novel benzisothiazolin-3-one derivative, 2-(benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) acetamide(8), was synthesized from the initial compound benzo[d]isothiazol-3(2H)-one(BIT) 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed the target compound exhibited a good anti-microbial activity.     

Synthesis of 2-Benzylidene and 2-Hetarylmethyl Derivatives of 2H-1,4-Benzoxazin-3-(4H)-ones as Neuroprotecting Agents

A wide variety of the title compounds were synthesized by conventional and microwave methods in which the main step is a condensation of an aldehyde with a 1,4-benzoxazin-3-(4H)-one. In all cases, the Z diasteromers were the major products. Of particular importance is the synthesis of novel 2-(3,5-dibromo-4-hydroxy) and 2-(4-acetoxy-3,5-dibromobenzylidene derivatives of 2H-1,4-benzoxazin-3-(4H)-ones, four of which were shown in a previous publication to exhibit potent neuroprotecting properties. The yields of titled compounds ranged from 25 to 83%.     

6-(4-取代苯基)-5-甲基-4,5二氢-3(2H)哒嗪酮化合物的合成及其抑制血小板聚集作用

血小板聚集在血栓形成中起着先导而关键的作用,而严重威胁人类生命健康的心脑血管疾病多数与血栓形成和血栓栓塞有着密切的联系[1]。二氢哒嗪酮类化合物对抑制血小板聚集有较强的药理活性,对二磷酸腺苷(ADP)、花生四烯酸(AA)、血小板活化因子(PAF)和胶原(Collagen)引起的血小板聚集均有抑制作用。深入研究二氢哒嗪酮类化合物的构效关系,以期寻找活性更强的抗血小板聚集药物,是开发新型心脑血管系统疾病药物的重要研究方向之一。本文设计合成了6-(4-取代苯基)-5-甲基-4,5二氢-3(2H)哒嗪酮类化合物[2,3,4],并进行了体外药理实验。1实验部…     

One-pot Multicomponent Synthesis,Spectroscopy, Crystal Structures and Theoretical Calculations of 3-Cyano-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-2(1H)-pyridinone and 3-Cyano-4-chlorophenyl-6-(4-tolyl)-2(1H)-pyridinone

Pyridinone derivatives are of great interest in medicinal chemistry where they were found to be potent to various diseases. Their metal complexes added more value to their applications. Here, we have synthesized two 2-pyridinone derivatives(3-cyano-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-2(1 H)-pyridinone and 3-cyano-4-chlorophenyl-6-(4-tolyl)-2(1 H)-pyridinone) using one-pot multicomponent system. They were well characterized using spectroscopic techniques like nuclear magnetic resonance(NMR-1 H 13 C), Fourier transform infrared(FT-IR) and UV/Vis spectroscopy. The final structures were determined using single-crystal X-ray diffraction technique which helps us to determine their geometries. Density functional theory(DFT) and time-dependent density functional theory(TD-DFT) with suitable basis-sets of calculations have correctly simulated these spectroscopic parameters. The intramolecular charge transfer(ICT) of both substrates has been discussed using natural bond orbital(NBO) technique. Molecular electrostatic potential(MEP) surfaces showed their reactive locations for intermolecular charge transfer. Compared to p-nitroaniline(pNA), both substrates were shown to have substantial molecular hyperpolarizability.     

1,5-二取代吡唑基-1,4-戊二烯-3-酮类化合物的合成及生物活性研究

设计合成了13个未见文献报道的1,5-二取代吡唑基-1,4-戊二烯-3-酮类化合物, 其结构经元素分析, 1H NMR, IR确证. 初步生物活性测试结果表明, 部分化合物有一定的抗烟草花叶病毒(TMV)活性, 所有化合物抑菌活性较低.     

Synthesis of Novel 2-(4-Oxo-3,4- Dihydroquinazolin-2-Ylsulfinylmethyl)-3H-Quinazolin-4-One

Abstract

Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave 4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3) gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). Oxidation of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4- dihydroquinazolin-2-ylsulfinyl methyl)-3H -quinazolin-4-one) (5). The entire sequences of reactions in this work have been carried out using eco-friendly solvents and green conditions.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis of azoles from 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides

Condensation of 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides with 2,4-pentanedione, phenyl isocyanate or phenyl isothiocyanate (with subsequent work up of the semicarbazides obtained by base), and carbon disulfide gave respectively: 1-(3,5-dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl)-3-oxopropylanilino]-1-propanone, 3-(2-{[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-5-one and its thio analog, and 5-(2-{[2-(2-thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl)ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-oxadiazole-2(3H)-thione plus their methyl derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1353–1358, September, 2007.     

Synthesis and pharmacological activity of 4-(4'-(chlorophenyl)-4-hydroxypiperidine) derivatives

A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.