Synthesis of some novel azo derivatives of 3,5-dimethyl-1-(2-hydroxyethyl)pyrazole as potent analgesic agents

A series of 1-(2-hydroxyethyl)-3,5-dimethylpyrazolylazo derivatives, incorporating thiosemicarbazide 2a-c, 1,3,4-thiadiazole 3a-c, and 1,2,4-triazole-3-thione 4a-c were synthesized. The structure of these novel synthesized compounds 2a-c, 3a-c, and 4a-c was confirmed by spectral analysis. All these compounds were screened for their analgesic activity. Hot-plate and tail-immersion tests were used for the determination of the analgesic activity. Morphine, an analgesic through both spinal and supraspinal pathways, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg i.p. Among the compounds, 2-(butylamino)-5-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-1,3,4-thiadiazole 3a and 4-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-4-(2-phenethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 4c showed analgesic effects in both tests. Especially 4c exerted strong analgesia starting at 30 min after injection.     

Synthesis and evaluation of 4-(substituted)-acetylamino-3-mercapto-5-(4-substituted) phenyl-1,2,4-triazole derivatives as antimicrobial agents

Triazoles and its derivatives are found to possess diverse applications in the field of medicine and industry. A series of novel 1,2,4-triazole derivatives have been synthesized as novel antimicrobial agents starting from different 4-substituted benzoic acids. The chemical structures of these newly synthesized compounds were elucidated by Fourier transform infrared spectroscopy (FTIR), ¹H NMR, ¹³C NMR, FAB⁺-MS spectral data, and elemental analysis. Their antimicrobial activities were investigated against four bacterial strains S. aureus (ATCC-25923), P. aeruginosa (ATCC-27853), E. coli (ATCC-8739), B. subtilis (ATCC-6633) and three fungal strains C. albicans (MTCC-227), A. niger (MTCC-3323), and F. oxysporum (MTCC-2087). Preliminary results indicate that some of them exhibit promising activities and deserve further consideration.     

Synthesis of thiadiazol derivatives of 4(3H)-quinazolinone as potential antimicrobial agents

Three series of quinazolinone derivatives were synthesised namely: 3-[4-(2-substituted amino-1,3,4-thiadiazol-5-yl)phenyl]-2-methyl-4-(3H)- quinazolinones; 3-[4-(2-substituted amino-1,3,4-thiadiazol-5-yl)anilino]-2-methyl-4-(3H)- quinazolinones and 3-[(2-substituted amino-1,3,4-thiadiazol-5-yl)methyl]-2-methyl-4(3H)-quinazolinones. The antimicrobial activity of representative compounds of these series as well as of the starting quinazolinone acids was studied.     

Synthesis and characterization of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives as potent antimicrobial and hydrogen peroxide scavenging agents

A series of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives were synthesized by coupling isoniazid with differently substituted aldehydes and benzophenones in the presence of absolute ethanol along with catalytic amount of glacial acetic acid. The structure of all the synthesized compounds were confirmed and characterized by using various spectral technique like IR, 1H NMR, 13C NMR and mass spectroscopy. All the synthesized compounds were evaluated for their antimicrobial activity in terms of zone of inhibition, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration in camparison to the standard drugs. The results revealed that all synthesized compounds had shown potent to mild biological activity. Among the synthesized derivatives, (E)-N'-(3,4-dimethoxybenzylidene)isonicotinohydrazide 2e, (E)-N'-(3,4,5-trimethoxybenzylidene)isonicotinohydrazide 2f and (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide 2g were found to be the most effective antimicrobial compounds, whereas compounds 2g and 2k were the most potent antioxidants with significant hydrogen peroxide scavenging activity.     

Synthesis and pharmacological evaluation of some novel 4-isopropyl thiazole-based sulfonyl derivatives as potent antimicrobial and antitubercular agents

A series of novel sulfonyl derivatives 3-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazoles 4a–4e, isopropyl thiazole-derived schiff bases 8a–8l, and 2-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-1,3,4-oxadiazoles 11a–11e were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, elemental, and mass spectral analysis. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv ascertain compounds 4e, 8b, and 8f as excellent antitubercular molecules, when compared with first line drug isoniazid (0.25 μg/mL).     

Synthesis of new 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antimicrobial agents

New (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 6 (pyrazolic chalcones) were synthesized from Claisen–Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 5. Subsequently, the cyclocondensation reaction of chalcones 6 with phenylhydrazine in acetic acid medium afforded the new 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7. The synthesized compounds were characterized by spectral studies and evaluated for their in vitro antibacterial activity against three pathogenic bacterial strains, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and in vitro antifungal activity against three pathogenic fungal strains Aspergillus flavus, Chrysosporium keratinophilum, and Candida albicans.     

Synthesis of certain N-aryl-N′-(2-pyrimidinyl) guanidine derivatives as potential antimicrobial agents

N-Aryl-N′-(4-hydroxy-6-methyl-2-pyrimidinyl) guanidines (IIa-c) were prepared by cyclization of N-arylbiguanides (Ia-c) with ethyl acetoacetate. Coupling of compounds (IIa-c) with the appropriate diazotized arylamine gave N-aryl-N′-(5-arylhydrazono-6-methyl-4-oxopyrimidin-2-yl) guanidines (IIIa-f). Whereas, their chlorination with phosphorus oxychloride followed by treatment of N-aryl-N′-(4-chloro-6-methyl-2-pyrimidinyl) guanidines (IVa-c) with the appropriate arylamine afforded the corresponding 4-arylamino derivatives (Va-f). Compounds (IIIa-f) were also formed when compounds (Ia-c) were treated with ethyl 2-arylhydrazono-3-oxobutyrates. The antimicrobial testing of some of the prepared compounds against some pathogenic microorganisms revealed that only two have a marked effect against.Escherichia coli.     

Synthesis and biological evaluation of novel 4,5-dihydropyrazole derivatives as potent anticancer and antimicrobial agents

A focused library of 4,5-dihydropyrazole dervivatives (4, 5, 6, 7a–h, 8, 9a–g, and 10a–g) were synthesized from novel 5-(2,6-difluorophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbothioamide 4. The synthesized compounds were characterized using elemental analysis and spectral data (IR, mass spectra, ¹H and ¹³C NMR) and evaluated for antimicrobial activity by broth dilution method and in vitro anticancer activity. Among the synthesized compounds 7a, 9c, 9g, and 10d exhibit broad spectrum antimicrobial activity against tested microbial strains. The in vitro cancer results ascertain 7a, 9c, and 10d are most potent molecules in comparison to reference standard cisplatin.     

Synthesis and antiinflammatory activities of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones

A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones was synthesized and evaluated as candidate antiinflammatory/analgesic agents as well as dual inhibitors of prostaglandin and leukotriene synthesis. Some compounds that showed dual inhibitory activity were found to possess equipotent antiinflammatory activities to indomethacin, with reduced ulcerogenic effects. One of the compounds, N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne, was found to have a wider safety margin than indomethacin or piroxicam, and was selected for detailed evaluation as a candidate drug for clinical application.     

含查尔酮结构N-取代饶丹宁衍生物的合成及抗菌活性研究

目的设计合成两个系列含L-异亮氨酸或L-色氨酸结构的饶丹宁与查尔酮拼合衍生物（4a-4n和5a-5n）,并对其进行体外抗菌活性评价。方法以取代苯乙酮为原料,经缩合反应和Knoevenagel反应得到目标化合物。采用连续稀释法,以诺氟沙星和苯唑西林为阳性对照药,选取7种金黄色葡萄球菌（＆aureusRN4220、＆aureusKCTC503、＆aureusKCTC209、MRSACCARM3167、MRSACCARM3506、QRSACCARM3505、QRSACCARM3519）和大肠杆菌（Ecoli1356）为测试菌株对目标化合物进行体外抗菌活性评价。结果与结论合成了28个未见文献报道的新化合物：（2R）-3-甲基-2-（（Z）-4-氧代-5-（4-（（E）-3-取代苯基-3-氧代丙-1-烯基）苯亚甲基）-2-硫代噻唑烷-2,4-二酮-3-基）戊酸（4a～4n）和（尺）-3-（1H-吲哚-3-基）-2-（（Z）-4-氧代-5-（4-（（E）-3-取代苯基-3-氧代丙-1-烯基）苯亚甲基）-2-硫代噻唑烷-2,4-二酮-3一基）丙酸（5a-5n）。两个系列化合物的结构经1H-NMR和IR谱确证。体外活性测试结果显示,所合成的大部分化合物具有较好的抗菌活性,其中,化合物4n、5g和5j的抗菌活性最好,它们对4种耐药菌的MIC值均为2μg·mL-1。     

Synthesis and pharmacological evaluation of novel 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one derivatives as potential antimicrobial agents

Novel compounds of biological interest were synthesized by in situ reduction of Schiff’s base of 5,6-dimethoxy indanone and 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one in the presence of Ti(OiPr)₄ and NaBH₃CN. Further alkylation using different alkyl/aryl halides in the presence of NaH in DMF gave a series of novel compounds. A formation of newly synthesized compounds was confirmed on the basis of their spectral and elemental analysis. Further these compounds were screened for their antimicrobial activity and found to have promising antibacterial and antifungal activity.     

Synthesis and antiinflammatory activity of acyl derivatives of 4-amino- and 4-(isopropylamino)antipyrine

Pharmaceutical Chemistry Journal -     

Synthesis of alkyloxybenzamide derivatives as potential antimicrobial agents

Three series of alkyloxybenzamido derivatives have been prepared. The first comprises N1-[4-(4-alkyloxybenzamido)benzoyl]-N2-substituted alkylidene hydrazine, the second involves 1-[4-(4-alkyloxybenzamido)benzoyl]-4-alkyl, aryl, or aralkyl-3-thiosemicarbazides, and the third includes 1-substituted-5-[4-(4-alkyloxybenzamido)phenyl]-1,3,4-triazole-2-t hione. Representative samples of the prepared compounds were tested for their in-vitro antimicrobial activity.     

Synthesis of benzimidazole derivatives as potential antimicrobial agents

Three novel series of benzimidazol derivatives were prepared. Namely; 2-alkyl-1-(4-substituted-4H-1,2,4-triazole-5-thion-3-yl)methylb enzimidazoles; 2-alkyl-1-(5-substituted amino-1,3,4-thiadiazol-2-yl)methylbenzimidazoles; and 2-alkyl-1-[(3,4-disubstituted thiazolin-2-ylidene)hydrazinocarbonyl] methylbenzimidazoles. The antimicrobial testing of the prepared compounds as well as of the key intermediate thiosemicarbazides was performed.     

Synthesis of new quinoline derivatives as antimicrobial agents

2-Hydroxyquinoline-4-hydrazide was condensed with some aromatic aldehydes and acetophenones to give the hydrazones 1a-h. It was also reacted with HCOOH, PhCOCl and p-CH3O-PhCOCl to afford 2a-c. Cyclization of 2b was completed by using PPA, POCl3 and/or P2S5, which gave compounds 3, 4, and 6 respectively. Reaction of 4 with some amines gave the corresponding derivatives 5a-f. The thiosemicarbazide 7 was cyclized under acid and basic condition to give the thiadiazolyl-8 and triazolyl-10 derivatives.     

Synthesis of some new glutamine linked 2,3-disubstituted quinazolinone derivatives as potent antimicrobial and antioxidant agents

A series of novel glutamine linked 2,3-disubstituted quinazolinone conjugates was synthesized from methyl anthranilate and different substituted acids and acid chlorides. The compounds 5a–l were prepared in good yields. All compounds were screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against Candida albicans and Aspergillus flavus using paper disk diffusion technique. The minimum inhibitory concentrations of the compounds were also determined by agar streak dilution method. The compound 5b was found to exhibit the most potent in vitro anti-microbial activity. When tested for their antioxidant activity, compounds 5i and 5l showed potent radical scavenging activity, while compound 5g had moderate effect against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, nitric oxide, and superoxide radical scavenging assays. These results suggest that, the three quinazolinone analogs (5g, 5i, and 5l) could be considered as useful templates for future development to obtain more potent antioxidant agents.