Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones

A variety of novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines, the starting material dithiocarbamate was synthesized from methylanthranilate. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, the compounds A1, A2, A3 and A4 shown more potent analgesic activity, and the compound A4 shown more potent anti-inflammatory activity than the reference diclofenac sodium.     

Synthesis of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 3-butyl-2-hydrazino-3H-quinazolin-4-one with various aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 3-butyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (AS3) emerged as the most active analgesic agent. Compound 3-butyl-2-(1-ethylpropylidene-hydrazino)-3H-quinazolin-4-one (AS2) emerged as the most active anti-inflammatory agent and is moderately more potent when compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Synthesis and pharmacological evaluation of some 3-(4-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of 3-(4-methyl phenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-methyl phenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(4-methyl phenyl)-3H-quinazolin-4-one was synthesized from 4-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. While the test compounds exhibited significant activity, compounds Al, A2, and A3 showed more potent analgesic activity and the compound A3 showed more potent anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Synthesis,analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4(3H) ones

A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium.     

Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methyl-3-substituted quinazolin-4-(3H)-ones

A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The compounds synthesized were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown more potent analgesic activity, and the compounds VA3 and VA4 shown more potent anti-inflammatory activity than the reference compound diclofinac sodium.     

Synthesis and analgesic, anti-inflammatory activities of 3-(3-methoxyphenyl)-2-substituted amino-quinazolin-4(3H)-ones

A variety of novel 3-(3-methoxyphenyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methoxyphenyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methoxyphenyl)-quinazolin-4(3H)-one was synthesized from 3-methoxy aniline. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic behavior. Among these the compound 2-(1-methyl butylidene-hydrazino)-3-(3-methoxyphenyl)-3H-quinazolin-4-one (AS3) emerged as the most active compound for the analgesic activity, while the compound 2-(1-ethyl propylidene-hydrazino)-3-(3-methyoxyphenyl)-3H-quinazolin-4-one (AS2) showed most potent anti-inflammatory activity of the series and these compounds are moderately more potent when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.     

Synthesis and pharmacological evaluation of some 3-(2-methylphenyl)-2-substituted amino-quinazolin-4(3H)-ones as analgesic and antiinflammatory agents

A variety of novel 3-(2-methylphenyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(2-methylphenyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(2-methylphenyl)-quinazolin-4(3H)-one was synthesized from 2-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. Among these, the compound 2-(1-ethylpropylidene)-hydrazino-3-(2-methylphenyl)-quinazolin-4(3H)-one emerged as the most active compound for analgesic activity, while the compound 2-(1-methylbutylidene)-hydrazino-3-(2-methylphenyl)-quinazolin-4(3H)-one showed most potent anti-inflamma-tory activity of the series and was moderately more potent in its anti-inflammatory activity when compared to the reference standard diclofenac sodium (CAS 15307-86-5). Interestingly, the test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid (CAS No: 50-78-2).     

Synthesis and pharmacological investigation of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one was synthesized from 3-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. Compound 2-(1-ethylpropylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS2) was the most active analgesic agent. Compound 2-(1-methylbutylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS3) was the most active anti-inflammatory agent and was moderately more potent than the reference standard diclofenac sodium. The test compounds showed only mild ulcerogenic potential compared with aspirin.     

Synthesis,analgesic and anti-inflammatory activities of some novel 2,3-disubstituted quinazolin-4(3H)-ones

A series of novel 2-benzylamino-3-substituted quinazolin-4(3H)-ones have been synthesized by treating 3-amino-2-benzylamino quinazolin-4(3H)-one, with different aldehydes and ketones. The starting material 3-amino-2-benzylamino quinazolin-4(3H)-one was synthesized by nucleophilic substitution of thiomethyl group of 3-amino-2-methylthio quinazolin-4(3H)-one by benzylamine. The title compounds were investigated for analgesic and anti-inflammatory activities. All the test compounds exhibited significant analgesic activity, whereas the compound III is equipotent with diclofenac sodium. The compounds I, II and III showed more potent anti-inflammatory activity than diclofenac sodium.     

Synthesis,anti-inflammatory and analgesic activities of arylidene-2-(3-chloroanilino)nicotinic acid hydrazides

A new series of 2-(3-chloroanilino)nicotinic acid hydrazides 12a–p were synthesized and evaluated for their anti-inflammatory and analgesic activities. Most of the compounds have shown anti-inflammatory activity with a moderate-to-excellent activity range. Among them, 3-chloro 12d and 4-methoxyphenyl derivatives 12i exhibited the most potent anti-inflammatory activity relative to niflumic acid as the reference drug (95, 87, and 81 % reductions in inflammation, respectively). The compounds with the highest anti-inflammatory activity were subjected to analgesic assay and showed moderate-to-excellent analgesic activities. The 2,4-dimethoxyphenyl derivative (12j) exhibited the highest analgesic activity relative to niflumic acid (99.6 and 68 % activity, respectively).     

Synthesis and pharmacological investigation of 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones as analgesic and anti-inflammatory agents

In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid.     

Synthesis and evaluation of analgesic, anti-inflammatory and antioxidant activities of new 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones

A new series of 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones have been obtained starting from 5-methyl-2(3H)-benzoxazolone. All the compounds have been characterized by IR, 1H-NMR and mass spectroscopy. The new compounds were screened for analgesic and anti-inflammatory activities and ulcerogenic effect. The in vitro antioxidant capacity of the synthesized compounds were tested by the nitric oxide radical scavenging assay. Most of the compounds showed antiinflammatory activity. Among them, 3-[4-(4-fluorophenyl)piperazinomethyl] -6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) was found more potent than the reference drug indometacin (CAS 53-86-1) with 41.66% decrease in edema. Compared with the control, some of the compounds exhibited analgesic effects. Similar to the anti-inflammatory activity results, compound 3j showed the highest analgesic profile with 48.56% inhibition. No active hemorragic focus was observed in the microscopic evaluation in the ulcerogenic effect studies of the tested compounds. 6-(3-Chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (2b) and 3-[4-(4-fluorophenyl-piperazino)methyl]-6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) showed nearly maximum antioxidant activity compared to ascorbic acid (CAS 50-81-7) with IC50 values of 27.6 and 30.1 microg/mL, respectively.     

Synthesis and pharmacological investigation of novel 3-(benzyl)-2-substituted amino-3<Emphasis Type="Italic">H</Emphasis>-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of novel 3-(benzyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-benzyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-benzyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from benzyl amine. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. The compound 3-benzyl-2-[N’-(1-ethyl-propylidene)-hydrazino]-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Microwave-assisted synthesis and evaluation of anti-inflammatory activity of new series of N-substituted 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde derivatives

A series of N-substituted 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde derivatives bearing potentially bioactive substituents were synthesized by microwave irradiation method in good yield compared with conventional method. The synthesized compounds were screened for their anti-inflammatory activity and were compared with a standard drug. The compounds demonstrated potent to weak anti-inflammatory activity. Of the compounds studied, compounds 6i and 6d showed potent activity comparable to the standard drug ibuprofen at the same dose in carrageenan-induced paw edema in rat model.     

Amide derivatives of [6-(5-methyl-3-phenylpyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acids as potential analgesic and anti-inflammatory compounds

In this study, amide derivatives of [6-(5-methyl-3-phenyl-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were synthesized and tested for their in vivo analgesic and anti-inflammatory activity by using the p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a, 6d, 6e, 6g, 6h and 6m were more potent than that of aspirin as an analgesic and indomethacin as an anti-inflammatory drug, respectively. The other derivatives generally resulted in comparable activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro human whole blood assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and other mechanisms might be involved.     

Synthesis and analgesic and anti-inflammatory activity of some new (6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid residues

In this study for developing potent analgesic and anti-inflammatory compounds, we synthesized 6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid side chain, and performed preliminary screening of their in vivo analgesic and anti-inflammatory activities at a single dose of 100 mg/kg inmice by a p-benzoquinone-induced writhing test and a Carrageenaninduced hind paw edema model, respectively. We also determined their gastric ulceration effects in the tested animals. Propanoic acid derivatives were generally found to have higher analgesic and anti-inflammatory activities, and among them, 3-(6-benzoyl-2-benzothiazolinon-3-yl)propanoic acid (Compound 4 a) exhibited the highest analgesic and anti-inflammatory activity. However, all compounds showed lower anti-inflammatory effects than we observed for indomethacin at 10 mg/kg dose. Consequently, 6-acyl-2-benzoxazolinone/2-benzothiazolinones having propanoic acid side chain might lead to further studies for developing better candidates with potent analgesic and anti-inflammatory effects while acetic acid derivatives do not exhibit comparable satisfactory features.     

Synthesis and evaluation of analgesic,anti-inflammatory and antimicrobial activities of 6-acyl-3-piperazinomethyl-2-benzoxazolinones

In this study, 16 new 6-difluorobenzoyl-3-piperazinomethyl-2-benzoxazolinones were synthesized by Mannich reaction. Their chemical structures were proven by IR, 1H-NMR and elemental analysis. The compounds were screened for their analgesic and anti-inflammatory activities. A modified Koster test, using acetylsalicylic acid (ASA, CAS 50-78-2) as the reference drug, was used to assess analgesic activity. The anti-inflammatory activity was evaluated by the carrageenan induced hind-paw oedema test. The analgesic activities of all compounds were higher than their anti-inflammatory activities and therefore the prominent analgesic actions of the compounds are thought to be due to a central effect. The microbiological effects of the compounds were evaluated in vitro against various pathogenic fungi and bacteria using the microdilution method. Most of the compounds were found to be inactive against bacteria and fungi. One of the compounds (31) possessed considerable analgesic activity as well as moderate antibacterial activity against S. aureus. Another compound (3m) showed analgesic and antifungal activities comparable to those of ASA and fluconazole (CAS 86386-73-4), respectively.     

Synthesis and analgesic-anti-inflammatory activities of some 1,2,4-triazine derivatives

A variety of novel N-arylidene-N'-[5-(4-isobutylphenyl)-[1,2,4]-triazin-3-yl] hydrazines 4, carboxylic acid N'-[5-(4-isobutylphenyl)-[1,2,4]-triazin-3-yl] hydrazides 5, triazolotriazines 6 and other related triazine derivatives were synthesized. Several synthetic routes were employed to access the desired compounds from 5-(4-isobutylphenyl)-[1,2,4]-triazin-3-yl hydrazine 3 as a parent compound. The analgesic and anti-inflammatory activities of the synthesized compounds were studied. The results showed that compound 4 g exhibited pronounced analgesic activity, while compound 4f displayed the highest anti-inflammatory activity. Meanwhile, compound 6d evoked dual analgesic-anti-inflammatory effect without any ulcerogenicity.     

Synthesis and Pharmacological Investigation of 5-Substituted-3-methylsulfanyl-1H-pyrazole-4-carboxylic Acid Ethyl Esters as New Analgesic and Anti-inflammatory Agents

To synthesize a new series of 5-substituted-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl esters for their analgesic and anti-inflammatory activity.The title compound synthesized by reacting the amino group of 5-amino-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl ester with acid anhydrides, acid chlorides and phenyl dithiocarbamates. The synthesized compounds were characterized by IR, 1H-NMR and mass spectral data; the purity of the compounds was determined by elemental analysis. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behaviour.The compound 5-benzoylamino-3-methylsulfanyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (4c) emerged as the most active compound and exhibiting imperative analgesic and anti-inflammatory activities. Interestingly the test compounds showed only mild ulcerogenic potential when compared to indomethacin.The compound (4c) could serve as a lead molecule for further modification to obtain a clinically useful novel class of analgesic and anti-inflammatory agents.     

Synthesis and investigation of anti-inflammatory activity of novel nitric oxide donating hybrid drugs

A small library of nitric oxide donating groups, 4-acetamidophenyl-2-[{2-(nitrooxy)ethyl}(phenyl) amino]benzoate (5a–e) possessing a variety of substituents (–H, –NO₂, –CH₃, –acetamidophenyl, –SO₂NH₂) attached to the fourth position of phenyl ring were synthesized and evaluated for anti-inflammatory, analgesic and ulcerogenic potential. Structure–activity relationship data showed that the 2-phenylaminobenzoic acid skeleton is required for selective COX-2 inhibition. Among all compounds 4-acetamidophenyl-2-[{2-(nitrooxy)ethyl}(phenyl)amino]benzoate (5a) has shown potent anti-inflammatory activity while 4-acetamidophenyl-2-[{4-{(4-acetamidophenoxy)carbonyl} phenyl}{2-(nitrooxy)ethyl}amino]benzoate (5d) has shown potent analgesic activity compared to standard drug diclofenac.