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 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 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 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.     

Synthesis and H1-antihistaminic activity of some novel 1-substituted-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones

A series of novel 1-substituted-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones were synthesized by the cyclization of 2-hydrazino-3-(3-methylphenyl) quinazolin-4(3H)-one with various one carbon donors. The starting material 2-hydrazino-3-(3-methylphenyl)quinazolin-4(3H)-one, was synthesized from 3-methylaniline by a novel innovative route. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly, whereas the compound 1-methyl-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-one II was found to be equipotent (percent protection 70.0%) with the reference standard chlorpheniramine maleate (percent protection 71%). Compound II show negligible sedation (7%) when compared to chlorpheniramine maleate (25%). Hence it could serve as prototype molecule for further development as a new class of H(1)-antihistamines.     

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

A variety of novel 2-butyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-butyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines; the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, compounds A1, A2, A3 and A4 showed more potent analgesic activity and compound A4 showed more potent anti-inflammatory activity than the reference 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 pharmacological investigation of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as a new class of H1-antihistamine agents

A series of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones was synthesized by the cyclization of 2-hydrazino-3-(4-substituted phenyl)-3H-quinazolin-4-one with various one-carbon donors. The starting material, 2-hydrazino-3-(4-substituted phenyl)-3H-quinazolin-4-one, was synthesized from 4-substituted aniline by a novel innovative route. When tested for in-vivo H1-antihistamine activity on conscious guinea-pigs, all the test compounds significantly protected the animals against histamine-induced bronchospasm. The compound 1-methyl-4-(4-chloro phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (VII) was more potent (72.71% protection), and 1-methyl-4-(4-methoxy phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) was equipotent (71% protection), when compared with the reference standard, chlorpheniramine maleate (71% protection). Compounds II and VII showed negligible sedation (5% and 8% respectively) when compared with chlorpheniramine maleate (25%). Compounds II and VII could serve as prototype molecules for further development as a new class of H1-antihistamines.     

Synthesis and pharmacological activities of novel 3-(isoxazol-3-yl)-quinazolin-4(3H)-one derivatives

Several new 3-(isoxazol-3-yl)-quinazolin-4(3H)-one derivatives were synthesized and tested for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effect. A few compounds were as active as phenylbutazone in the writhing and acetic acid peritonitis tests. They had a very low ulcerogenic effect.     

Synthesis and evaluation of novel prodrugs of naproxen

A series of novel prodrugs of naproxen has been synthesized. Naproxen (1) was reacted with thionyl chloride to yield acid chloride (2) which was further reacted with glucose to form the glucosyl naproxen (3). Tetra-acetate of glucosyl naproxen was prepared and finally reacted with different amino acids to yield the title compounds. These compounds were evaluated for analgesic, anti-inflammatory activities, and for possible GI toxicity. Compound 5b depicted most potent analgesic activity with percentage inhibition of 98.15%. Compound 5a was found to be most potent anti-inflammatory agent with 76% inhibition. Compound 5n was second most active analgesic (92.26%) and anti-inflammatory (73%) agent. In vitro hydrolysis pattern of synthesized prodrugs was studied in phosphate buffer of pH 7.4 and acetate buffers of pH 3.0, 4.0, and 5.0, respectively. Selected compounds were evaluated for their ulcerogenic potential and all the tested derivatives were significantly less irritating to gastric mucosa than the parent drug.     

3‐(3‐Ethylphenyl)‐2‐substituted hydrazino‐3H‐quinazolin‐4‐one Derivatives: New Class of Analgesic and Anti‐Inflammatory Agents

A new series of 3‐(3‐ethylphenyl)‐2‐substituted hydrazino‐3H‐quinazolin‐4‐ones were synthesized by reacting the amino group of 2‐hydrazino‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti‐inflammatory and ulcerogenic index behavior. The compound 2‐(N′‐3‐pentylidene‐hydrazino)‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one ( AS2 ) emerged as the most active compound in exhibiting analgesic activity and the compound 2‐(N′‐2‐pentylidene‐hydrazino)‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one ( AS3 ) emerged as the most active compound in exhibiting anti‐inflammatory activity; and these compounds are moderately potent when compared with the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared with aspirin.     

Synthesis and pharmacological activity of 3-substituted pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-ones

A series of 3-substituted pyridothienopyrimidin-4(3H)-ones has been synthesized from 2,7,9-trimethyl-4H-pyrido[3',2':4,5]thieno-[3,2-d] [ 1,3]oxazin-4-one. These compounds have been evaluated for analgesic, anti-inflammatory and antipyretic activities. The ulcerogenic effect of the compounds has been also studied.     

New thiazolidinyl analogs containing pyridine ring: synthesis, biological evaluation and QSAR studies

A series of pyridine derivatives of thiazolidin-4-ones (4a–4o) has been synthesized. Structures of these compounds were established on the basis of elemental analysis, IR, ¹H NMR, ¹³C NMR, and Mass spectral data. All the synthesized compounds have been evaluated for their anti-inflammatory and analgesic effects. The results showed that compound 2-[4-methylphenylimino]-5-(1H-pyridin-2-ylmethylidene)-1,3-thiazolidin-4-one (4d), 2-(2,4-dinitro-phenylhydrazinylidine)-5-(1H-pyridin-2-yl-methylidene)-1,3-thiazolidin-4-one (4h), and 2-[3-nitro-phenylimino]-5-(1H-pyridin-2-yl-methylidene)-1,3-thiazolidin-4-one (4j) exhibited good anti-inflammatory and analgesic activity. Compound 4h was found to be the most active compound of the series with an interesting dual anti-inflammatory and analgesic activity. Docking simulation was performed to position synthesized compounds into the active site of COX-2. The relationships of energy-based docking score with analgesic and anti-inflammatory activities were also investigated by linear regression method. The QSAR models with R ² of 0.621 and 0.740 were developed for analgesic and anti-inflammatory activities, respectively.     

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.     

Pharmacological screening for anti-inflammatory, analgesic activity of pyrazolyl derivatives along with molecular docking studies

The pyrazole derivatives were synthesized and pharmacologically evaluated for analgesic (tail flick) and anti-inflammatory (based on carrageenan-induced paw edema) activities. Compound 4k showed high potency as an anti-inflammatory agent after 3 and 4-h time intervals (P?<?0.001) equipotent to indomethacin. They were devoid of ulcerogenic potential when administered at a dose of 30?mg/kg. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the byproduct of lipid peroxidation. Further docking studies of titled compounds was done to understand key interactions responsible for observed inhibition of COX enzyme. The most active compound 4k was found to have ?11.192?kcal/mol, as the free energy of binding. Various other key interactions between the synthesized molecules and active site of COX-2 enzyme, responsible for the obtained pharmacological results were also reported. Most of the active compounds were docked well into the active sites of the receptor.     

Synthesis, analgesic, anti-inflammatory, and in vitro antimicrobial activities of some novel quinazolin-4(3H)-one derivatives

With the aim of developing potent analgesic, anti-inflammatory, and antimicrobial agents a series of novel quinazolin-4(3H)-one derivatives were synthesized and characterized by FT-IR, ¹H-NMR, mass spectroscopy and bases of elemental analysis. Tail-flick technique, carrageenan-induced foot paw edema test, and agar streak dilution test were performed for screening analgesic, anti-inflammatory, and in vitro antimicrobial activity, respectively. Moreover, all compounds were examined for its ulcerogenicity. Results revealed that entire series of compounds exhibited mild to good analgesic, anti-inflammatory, and antimicrobial activity with low to moderate ulcer index. The relationship between the functional group variation and the biological activity of the evaluated compounds were discussed. Compound 2-(2-(4-(trifluoromethyl)benzylidene)hydrazinyl)-N-(4-(2-methyl-4-oxoquinazolin-3(4H)-yl) phenyl) acetamide 5e was determined to be the most active compound.     

Synthesis and anti-inflammatory evaluation of new substituted 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole derivatives

A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3-carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)-one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3-disubstituted pyrazole moiety were synthesized on reaction with semicarbazide, thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohydrazide, 2-acetyl thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds, respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (2) as starting material. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The anti-inflammatory screening showed that most of the obtained compounds were found to have significant anti-inflammatory activities with prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg comparable to celecoxib as a reference control. The ulcer indices of all compounds are mainly in the safe level (UI = 2.10-4.27) except for compounds 9a and 14a, which were highly ulcerogenic.     

Synthesis and evaluation of anti-inflammatory and analgesic activity of 3-[(5-substituted-1,3,4-oxadiazol-2-yl-thio)acetyl]-2H-chromen-2-ones

A novel series of 3-[(5-substituted-1,3,4-oxadiazol-2-yl-thio)acetyl]-2H-chromen-2-one (7a–i) were synthesized by the condensation between the appropriately substituted 5-substituted-1,3,4-oxadiazolyl-2-thione (4a–i) derived from various existing NSAIDs and 3-(2-bromoacetyl)-2H-chromen-2-one (6) under reflux in the presence of sodium ethoxide. Structure of the synthesized compounds was established on the basis of physicochemical, elemental analysis, and spectral data. The title compounds were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 200 mg/kg bw. Among the series, four compounds 7c, 7e, 7f, and 7h were found to possess a significant anti-inflammatory and analgesic activity profile. In addition, these compounds were also found to possess a less degree of ulcerogenic potential as compared to standard NSAIDs.