对甲磺酰基苯丙烯酸异羟肟酸和酰脲衍生物的合成及抗炎活性

目的研究对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物的合成及其抗炎活性.方法 将对甲磺酰基苯丙烯酸转化成其异羟肟酸(Ⅳ)和酰脲衍生物(Ⅴ),评价Ⅳ和Ⅴ的抗炎活性以及连续经口服给药对大鼠胃肠道的影响.结果 合成了10个新化合物(Ⅳ1～Ⅳ5和Ⅴ1～Ⅴ5),其结构经IR、1H-NMR和MS确证.小鼠试验表明:Ⅳ1、Ⅳ4、Ⅳ5和Ⅴ1、Ⅴ3、Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当(P＞0.05);大鼠试验显示:Ⅴ3和Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当(P＞0.05),Ⅳ4、Ⅴ3和Ⅴ5的胃肠道损伤显著小于双氯芬酸钠(P＜0.01),与罗非昔布和CMC-Na相当(P＞0.05).结论 对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物抗炎活性较强,胃肠道不良反应小,值得深入研究.     

Synthesis and anti-inflammatory activity of certain piperazinylthienylpyridazine derivatives

In this study, a novel series of 2-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (3a-f), 2-(4-substituted piperazin-l-yl carbonylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (4a-c) and 2-[2-(4-substituted piperazin-l-ylcarbonylethyl)]-6-(thien-2-yl)-2H-pyridazin-3-ones (5a,b) were prepared from 6-(thien-2-yl)-2H- pyridazin-3-one (1). In addition, 3-(4-substituted piperazin-l-ylcarbonyl methyl thio)-6-(thien-2-yl) pyridazines (6a-c) and 3-[2-(4-substitutedpiperazin-1-ylcarbonyl ethylthio]-6-(thien-2-yl) pyridazines (7a,b) were synthesized. Furthermore, 5-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (12a,b) were prepared. The structures of the new compounds were confirmed by elemental analysis as well as by 1H-NMR, IR and MS data. Some of the newly prepared compounds were subjected to evaluation for their anti-inflammatory activity against carrageenan-induced paw edema at a dose of 10 mg/kg using indomethacin as the reference standard.     

Synthesis and anti-inflammatory activity of some pyrazole derivatives

A novel series of pyrazoles containing benzenesulfonamides, 1,3,4-oxadiazole-2-thiones, 4-substituted-1,2,4-triazole-3-thiones, and 2-substituted-1,3,4-thiadiazoles has been synthesized. Anti-inflammatory activity of some synthesized compounds was evaluated in vivo utilizing a standard acute carrageenan-induced paw edema method. The most active anti-inflammatory agents 3, 8f, and 10f were evaluated for ulcerogenic liability in rats compared to indomethacin and celecoxib as reference standards. Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.     

Synthesis and anti-inflammatory activity of some heterocyclic derivatives of phenothiazine

Some new 10-{[5'-amino-(1"-ace tyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-thiadiazol-2'-yl] methyl}-phenothiazines (11-16) and 10-{[5'-amino-(1"-acetyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazines (26-31) have been synthesized from 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-thiadiazol-2'-yl)]methyl}phenothiazines (5-10) and 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-oxadiazol-2'-yl)]methyl}phenothiazines (20-25), respectively. All these compounds of the present series have been screened in vivo for their anti-inflammatory and acute toxicity. Compounds 16 and 31 were found to be potent members of the present series, which showed 46.2% and 48.0% anti-inflammatory activity, respectively, at a dose of 50 mg/kg p.o., while standard drug, phenylbutazone, exhibited 44.52% anti-inflammatory activity at same dose. However, 10-{[5'-amino-(1"-acetyl-5"-(o-methoxyphenyl)-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazine (31) was found to be most active and less ulcerogenic compound of this series. The structure of these compounds have been elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis.     

Synthesis,anti-inflammatory and antioxidant activity of ring-A-monosubstituted chalcone derivatives

A library of ring-A-monosubstituted chalcone derivatives (4a–4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (¹H NMR, ¹³C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential.     

Synthesis and anti-inflammatory activity of 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives

New 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives 17-31 were synthesized by the acylation of amines 9-16 with acyl chlorides. Amines 9-16 were obtained from aryl ketones 1-8. Aryl ketones 1-8 were synthesized by the acylation of corresponding aromatic compounds. As it was preliminary predicted by PASS (Prediction of Activity Spectra for Substance) program, all 1-acylaminoalkyl-3,4-dimethoxy- and 3,4-diethoxybenzene derivatives possess anti-inflammatory activity. Activity of compounds 18, 19, 21, 24, 26, 27, 28, 29 was similar to that of acetylsalicylic acid or ibuprofen however their acute toxicity was less than that of mentioned anti-inflammatory drugs. A series of 1-acylaminoalkyl-3,4-dimethoxybenzene, 1-acylaminoalkyl-3,4-diethoxybenzene and 6-acylaminoalkyl-2,3-dihydro-1,4-benzodioxine derivatives have been synthesized. These compounds possess moderate or strong anti-inflammatory activity and low toxicity.     

1位芳基取代的青藤碱衍生物的合成和抗炎活性研究

目的 进行1位取代芳基的青藤碱衍生物的合成及体外抗炎活性研究。方法 以青藤碱为先导化合物,首先1位溴取代反应,然后通过Suzuki偶联反应对A环1位进行修饰,制得一系列取代芳基的青藤碱衍生物,所有化合物均经¹H-NMR、¹³C-NMR、MS结构确认;采用报告基因法研究青藤碱衍生物对NF-κB转录活性的影响。结果 Suzuki偶联反应得到的一系列化合物活性均优于对照药青藤碱。结论 筛选到的4f和4g可作为候选药物进行深入研究,对研发治疗风湿性关节炎药物具有重要意义。     

甘草次酸3位酯类衍生物的合成及其抗炎活性的研究

目的 研究甘草次酸3位酯类衍生物的合成及其抗炎活性.方法 以甘草次酸为原料,结合甘草次酸的构效关系,采用化学方法合成了氨基酸类化合物或咪唑杂环类化合物与甘草次酸结构单元构筑的N-乙酰氨基乙酸甘草次酸酯、N-乙酰-DL-α-氨基丙酸甘草次酸酯、N-乙酰-DL-蛋氨酸甘草次酸酯、咪唑-4-羧酸-5-甘草次酸酯和咪唑-4-羧酸-5-(11-脱氧甘草次酸)酯等5种甘草次酸3位酯类衍生物,并经IR、1HNMR、MS等确证其结构.以二甲苯引起的小鼠耳肿胀模型评价其抗炎活性.结果 所合成的衍生物对二甲苯致小鼠耳肿胀具有明显的抑制作用.结论 甘草次酸3位酯类衍生物具有明显的抗炎活性,抗炎活性接近于氢化可的松,部分化合物的抗炎活性高于氢化可的松.     

Synthesis and anti-inflammatory activity of 2-pyridyl-2-thiobenzothiazole derivatives.

A series of novel 2-pyridyl-2-thiobenzothiazole compounds was prepared and investigated by a number of in vitro methods in order to determine their anti-inflammatory properties. Results are discussed with reference to well known NSAIDs. (3-carboxy-2-pyridyl)-2-thiobenzothiazole had the most potent anti-inflammatory activity, being 1.34 times more active than indomethacin used as reference compound.     

Synthesis anti-inflammatory and anticancer activity evaluation of some pyrazole and oxadiazole derivatives

Pyrazole derivatives IIa–l have been synthesized by condensation of chalcones Ia–f with hydrazine hydrate and phenyl hydrazine under microwave irradiation in good yields. Oxadiazole derivatives IVa–f have been synthesized by condensation of N′-hydroxypicolinamidine, N′-hydroxy isonicotinamidine, N′-hydroxypyrazine-2-carboxamidine with 2,5 dimethoxybenzaldehyde and 3-methoxy-4-hydroxy benzaldehyde, respectively. Structures assigned to IIa–l and IVa–f are fully supported by correct spectral and analytical data. All compounds (IIa–l & IVa–f) have been screened for anti-inflammatory and anticancer activities. Compounds IIj, IIk, and IVb exhibited good anti-inflammatory activity, while, IIa, c, j, and IVd showed better anticancer activity against four and three cancer cell lines, respectively.     

Synthesis and biological evaluation of anti-inflammatory activity of 1,3 diphenyl propenone derivatives

A series of five chalcone derivatives were synthesized by Claisen–Schmidt condensation of acetophenone with appropriately substituted benzaldehyde in the presence of aqueous alkali. The synthesized compounds were characterized by their IR, NMR, and Mass spectral data. These compounds have been subjected to anti-inflammatory screening using the carrageenan-induced rat hind paw edema model. Chalcone derivatives at dose 25 mg/kg by oral route inhibited significantly the formation of edema. Chalcone posses a highly electrophilic α,β-unsaturated carbonyl moiety showed better anti-inflammatory activity.