Synthesis and activities of new 4-hydroxy benzoxazolone derivatives

<正>A series of new 4-substituted benzoxazolone derivatives were synthesized according to a convenient method,their anti-inflammatory and analgesic activities in vivo were evaluated.All of them were new compounds,the structures of all the synthesized compounds were confirmed by ~1H NMR,~(13)C NMR,ESI-MS and HR-MS.Most of the compounds exhibited anti-inflammatory activity.     

Synthesis of （1H）—3,4—Dithydropyrrolo[2,1—c][1,4]oxazin—1—one Derivatives

In search of new anti-inflammatory and analgesic agents,(1H)-3,4-dihydro-pyrrolo [2,1-c][1,4]oxazin-1-one(3) and its acyl derivatives were designed and prepared .Compound 3 was prepared by treatment of methyl 1-(2-bromoethyl) pyrrole-2-carboxylate with silver oxide and its derivatives were obtained by Friedel-Carftes reaction.Nine of 6-acyl derivatives of compound 3 were prepared.     

Design and synthesis of 4-(1-(4-chlorobenzyl)-2,3-dioxoindolin-5-yl)-1 -(4-substituted/unsubstituted benzylidene) semicarbazide:Novel agents with analgesic,anti-inflammatory and ulcerogenic properties

A new series of isatin semicarbazide derivatives(7a-7j) were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively.The ulcerogenicity was also determined for all the compounds.Some of the compounds showed moderate enhancement of the activity.Among the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.     

Microwave mediated synthesis of non-carboxylic analogues of ibuprofen with improved pharmacological activity

A series of 1,2,4-triazolo[3,4-b]-thiadiazoles were synthesized following microwave irradiation method and also by conventional method.Newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activities.     

Regioselective Synthesis and Base Catalyzed Transacylation of Substituted 1H—Pyrazole—4—carboxamides

New type of substituted 1H-pyrazole-4-carboxamides were obtained by regioselective synthesis under the catalysis of different based.The stuctures of the title compounds were confirmed by elemental analysis,^1H NMR,IR,MS and X-ray crystallography.Compounds 1 were transcaylated into their corresponding.Compounds 1 were transacylated into their corresponding amides 3 in the prsence of sodium hydride.Preliminary bioassays indicated that some compounds showed fungicidal activities against Rhizoctonia solani and Sclerotinia sclerotiorum.     

Synthesis and Biological Activities of 3—（2—Furyl）—4—aryl—1,2,4—triazole—5—thiones

A series of novel compounds 3-(2-furyl)-4-aryl-1,2,4-triazole-5-thiones have been synthesized.All the compounds were characterized by spectral data and elemental analysis. The preliminary biological test showed that some of them exhibited excellent plant-growth regulative activities.     

1，3—Dipolar Cycloaddition of Substituted Benzonitrile Oxide to 5—（R）—（1—Menthyloxy）—2（5H）—furanone

Several isoxazoline compounds were obtained by the 1,3-dipolar cycloaddition of benzonitrile oxide to 5-(R)-(1-menthyloxy)-2(5H)-furanone. The reaction condition was investigated preliminarily, the structures of these compounds have been established via the analysis of NMR data (involved NOEID or HMBC) and the reaction seems occurred regioselectively.     

Synthesis and bioactivities of some new 1H-pyrazole derivatives containing an aryl sulfonate moiety

A new series of 1H-pyrazole derivatives 5a-j bearing an aryl sulfonate moiety have been synthesized by a one-pot cyclo-condensation reaction of 2-(3-(dimethylamino)acryloyl)phenyl-4-methyl benzene sulfonates 4a-e and hydrazine hydrate or phenyl hydrazine in ethanol under reflux conditions.Some of the newly synthesized compounds were screened for their anti-inflammatory activity.All synthesized compounds were screened against Gram positive and Gram negative bacterial and fungal strains.The compound 5b was found to be a potent anti-inflammatory agent while the majority of the compounds were found to be active against microbial strains.     

Organic Synthesis in Ionic Liquids： Condensation of 3-Methyl-1- phenyl-5-pyrazolone with Carbonyl Compounds Catalyzed by Ethylenediammonium Diacetate （EDDA）

The derivatives of pyrazolone are important class of antipyretic and analgesic compounds1. 1-Phenyl-3-methyl-4-arylmethylene-5-pyrazolones are very useful inter- mediates in the synthesis of substituted pyrazolones, generally, which were prepared by the c…     

Fragmentation Mechanism of Trans—α—Aryl—β—enamino Esters

Electron impact-induced fragmentation mechanism of Trans-α-Aryl-β-enamino esters were investigated using mass-analyzed ion kinetic energy (MIKE) spectrometry and high resolution accurate mass data It was found that the main characteristic fragmentations of compounds studied were:an odd electron ion M^ -EtOH was formed by losing a neutral molecule of ethanol;and the skeletal rearrangements took place;and the ring opening reaction happened after losing a carbon monoxide;and the typical McLafferty rearrangement underwent in ester group.The cycliztion reation caused by losing neutral molecule of TsNH2 due to the ortho-effects of substituted group of gromatic ring was also observed.     

Synthesis of (1H)-3,4-Dihydropyrrolo[2,1-c][1,4]oxazin-1-one Derivatives

It has been found that some acyl derivatives of 1,2,3,4-tetrahydro-1-indolizin-1-one 1and (1H)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one 2 show remarkable anti-inflammatory and analgesic activities1,2. The interest in extending the study of structure-activity relationships and search of new potent anti-inflammatory and analgesic agents led us to design and synthesize (1H)-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one 3 derivatives. NO 1 NNHO2 87654321ONO3 A few examples of the p…     

Synthesis,molecular docking with COX 1& II enzyme,ADMET screening and in vivo anti-inflammatory activity of oxadiazole,thiadiazole and triazole analogs of felbinac

Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy. The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals. The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively). Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (6c) emerged as the most potent NSAID compound exhibiting the highest anti-inflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least severity index on gastric mucosa (0.20). Further, molecular docking on cyclooxygenase and in silico ADME-Toxicity prediction studies also supported the experimental biological results and indicated that 6c has a potential to serve as a drug candidate or lead compound for developing novel anti-inflammatory and analgesic therapeutic agent(s) with minimum toxicity on gastric mucosa.     

Synthesis of 3-methyl-substituted pyrazolotriazolopyrimidin-4-one and pyrazolothiazolopyrimidin-4-one derivatives

As a part of a research on anti-inflammatory analgesic compounds 3-methyl substituted pyrazolotria-zolopyrimidin-4-one and pyrazolothiazolopyrimidin-4-one derivatives were prepared by previously reported procedures. None of the compounds showed improved activity when compared with the previously reported unsubstituted analogs.     

Synthesis of 1-trifluoroacetyl-3-dialkylamino-methyl-5-monosubstituted benzimidazoline-2-thiones using trifluoroacetic acid as an acylating agent

1-Trifluoroacetyl-3-dialkylaminomethyl-5-monosubstituted benzimidazoline-2-thiones have been synthesized from p-substituted anilines which were acetylated with trifluoroacetic acid. The trifluoroacetanilides were nitrated, reduced and cyclised with carbon disulphide in the presence of alcoholic potassium hydroxide and finally treated with formaldehyde and suitable secondary amines to afford the Mannich bases. The compounds were characterised by their analytical and spectral (ir, pmr, ¹⁹F and mass) data. The synthesized compounds have been screened for anti-inflammatory and analgesic activity and found to be active.     

Synthesis and Characterization of Some Novel 3-Bromo-2-acetylthiophene Chalcones and Biological Evaluation of Their Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylate Derivatives

Novel chalcones 1-(3-bromothien-2-yl)-3-(aryl)prop-2-en-1-ones derived from 3-bromo-2-acetylthiophene and their cyclization product with ethylacetoacetate such as 4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylate derivatives were synthesized and studied by X-ray, analytical, and spectral methods. Compounds were screened for their anti-inflammatory, analgesic, and antimicrobial activities. The compound ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-propoxyphenyl) cyclohex-3-ene-1-carboxylate 5c exhibited promising anti-inflammatory, analgesic and antibacterial activities.     

Synthesis and evaluation of analgesic and anti-inflammatory activities of most active free radical scavenging derivatives of embelin-A structure-activity relationship

Antioxidant and related properties of the plant Embelia ribes and embelin are well known. In the present study embelin was condensed with various aromatic substituted primary amines to yield ten new and one reported derivatives along with monomethyl embelin. All these compounds along with embelin were evaluated for in vitro antioxidant activity using 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and 2,2'-diphenyl-1-picryl hydrazyl (DPPH) methods. Two para-substituted embelin derivatives showed potent antioxidant activity. These compounds along with embelin were studied for analgesic and anti-inflammatory activities at 10 and 20 mg/kg doses by standard methods. Potent analgesic activity higher than the standard pentazocine was observed. Embelin and both of its derivatives almost completely abolished the acetic acid induced writhing. p-Sulfonylamine phenylamino derivative showed better anti-inflammatory activity than embelin.     

Microwave-assisted parallel synthesis of benzofuran-2-carboxamide derivatives bearing anti-inflammatory,analgesic and antipyretic agents

A series of benzofuran-2-carboxamides of biological and medicinal significance were synthesized by a microwave-assisted one-pot parallel approach via O-alkylation/Knoevenagel condensation. All the compounds were characterized and assayed for their in vivo anti-inflammatory, analgesic and antipyretic activities. The activity data of all compounds were listed and discussed in detail, among which some derivatives exhibited potent activities of particular interest.