二酰基双哌嗪双季铵盐类衍生物的合成及镇痛活性

目的：寻找活性强,毒性低的新型镇痛药物。方法：以1-甲基哌嗪为起始原料, 通过与不同的二酰氯反应得双二酰基哌嗪(IIIa-d), IIIa-d分别用不同的溴化物季铵化得6个新的1,1-二酰基-4,4,4′,4′-四烷基双哌嗪双季铵盐溴化物(IVa-f)。 结果：初步生物活性试验结果表明,这些化合物均有一定的镇痛和镇静活性, 尤其是IVe(剂量20 mg.kg^-1, 镇痛活性80.3%,镇静活性95.3%)和IVf(剂量0.5 mg.kg^-1, 镇痛活性75.5%,镇静活性53.8%)活性显著。结论：构效关系研究表明,两个季氮原子之间的距离对活性和毒性有较大影响,当n=4时, 活性最强,而毒性随两个季氮原子之间距离的减小而降低。苄基的引入可使活性明显增强,而且毒性降低。     

1,1-二烷基-4-(3-溴丙酰基)-哌嗪溴化物的合成及生物活性研究

设计合成了七种新的1,1-二烷基-4-(3-溴丙酰基)哌嗪季铵盐溴化物,通过IR,¹HNMR和元素分析证实其结构。初步生物活性试验结果表明,Ⅵa,Ⅵc和Ⅵe～g有明显的镇痛活性,Ⅵe～g还有较好的抗氧化SOD活性,但未发现有抗肿瘤作用。     

5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛活性

目的寻找高效低毒、有抗炎镇痛活性的新的吡咯里嗪酮类化合物。方法以二芳基取代杂环类COX-2选择性抑制剂为模板,以吡里酮为母体,设计并合成了5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物。用IR,¹HNMR和MS确定其结构。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定这些化合物的(po 200mg·kg^-1)抗炎及镇痛活性。结果合成了17个新化合物(1-17)。生物实验结果显示,多数化合物有一定的抗炎和(或)镇痛活性。结论化合物3,8,11,14和15抗炎活性优于对照药布洛芬;化合物9,10和11镇痛活性接近于对照药布洛芬,值得进一步研究。     

强啡肽A-(1-13)类似物的合成及生物活性

用固相多肽合成方法,合成了强啡肽A-(1-13)(I)及其类似物[Ala⁸,D-Pro¹⁰]-DYNA-(1-13)-NH₂(II)和[D-Ala²,Ala⁸,D-Pro¹⁰]-DYNA-(1-13)-NH2(III),并对其进行了镇痛活性试验和MVD及RVD试验。结果表明,合成产物均有镇痛活性,其中类似物III的镇痛活性是1的3.6倍,RVD试验活性比1强135倍,比已知的k-受体强激动剂U500488强11倍。     

5-芳基-1,2-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛作用

目的 研究5-芳基-1，2-二氢-1-吡咯里嗪酮类化合物的抗炎镇痛作用构效关系，寻找高效低毒、具有抗炎镇痛活性的新型吡咯里嗪酮衍生物。方法 以吡咯里嗪酮为母体，设计并合成了5-芳基-1，2-二氢-1-吡咯里嗪酮类化合物。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定了该类化合物的抗炎及镇痛活性。结果 用两条路线合成了10个目标化合物，经1H-NMR和MS确证其结构。小鼠试验表明，一些所合成的化合物具有明显的抗炎和／或镇痛作用。结论 化合物Ⅲ1及Ⅲ5的抗炎活性优于对照药布洛芬；化合物Ⅲ5的镇痛活性优于对照药布洛芬；其中化合物Ⅲ5的抗炎及镇痛活性均强于对照药布洛芬，值得进一步研究。     

3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚类衍生物的合成及其抗癌活性

目的　研究3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚类衍生物的合成及其抗癌活性。方法　通过亲电取代、羟醛缩合、选择性还原、相转移Wittig反应和水解反应合成目的化合物,利用几种药理模型进行抗癌和抗炎活性筛选。结果　设计合成了11个3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚化合物,均为新化合物。生物活性实验结果表明,化合物8对HL-60,HCT-8和Bel7402癌细胞株有效,且在浓度为10^-5mol·L^-1时,其抗炎抑制率可达100％。结论　化合物8显示了抑癌作用和抗炎活性,值得进一步研究。     

1,6-二(4-苯乙基-1-甲基-1-哌嗪基)己烷二溴化物镇痛作用及机制探讨

目的　研究哌嗪类新化合物1,6-二( 4-苯乙基1-甲基-1-哌嗪基)己烷二溴化物(97-9-G4)的镇痛作用及机制。方法　扭体法、热板法研究镇痛活性;联合给药观察纳洛酮、利血平、阿托品、CaCl₂和EDTA等对97-9G4镇痛作用的影响;并测定97-9-G4对小鼠体内PGE₂的影响。结果　sc 97-9-G4 5mg/kg即可有效抑制小鼠扭体反应(P<0.05) ;sc 40mg/kg和icv 2.5μg/kg均可明显延长热板实验的舔足阈(P<0.05) ;纳洛酮、CaCl₂和EDTA均可拮抗、减弱或加强其镇痛作用;利血平、阿托品对97-9-G4的镇痛作用影响不明显。结论　97-9-G4具有明显的镇痛活性,其镇痛作用与阿片受体及体内Ca²⁺等因素有一定关系。     

3-芳基-2-甲基-1-吡咯并[1,2-a]吡嗪酮类衍生物的合成和抗炎镇痛作用

目的研究3-芳基-2-甲基-1-吡咯并[1,2-a]吡嗪酮(2)类化合物抗炎镇痛作用的构效关系.方法通过吡咯-2-甲酸甲酯与α-溴代芳基乙酮的烃基化反应,制得1-(2-氧代-2-芳基)乙基吡咯-2-甲酸甲酯(4),4与甲胺反应经过环合直接生成目的化合物2;用小鼠测试了所合成化合物的抗炎镇痛活性.结果与结论合成了15个目标化合物;小鼠试验表明,一些所合成的化合物具有明显的抗炎和/或镇痛作用,其中化合物2o的作用活性与阳性对照药布洛芬相似.     

新型含羟基E,E-1-(3′-吲哚基)-5-取代苯基-1，4-戊二烯-3-酮化合物的合成及抗炎活性

目的寻找新的非甾体抗炎药物。方法利用羟醛缩合反应，合成了8个新型含羟基的E,E-1-(3′-吲哚基)-5-取代苯基-1，4-戊二烯-3-酮化合物，通过¹H NMR，ESI-MS和元素分析对其结构进行表征。并测定了体外抗炎活性。结果体外抗炎活性测试结果表明，所有化合物都有一定程度的抗炎活性。结论其中化合物4d和4e具有较强的抗炎活性，其抗炎活性与白藜芦醇接近，值得进一步研究。     

3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物的合成及抗炎镇痛作用

目的研究(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物抗炎镇痛作用的构效关系。方法以2-吡咯甲酸甲酯为原料,经取代、环合,制备(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮(3);通过Friedel-Crafts酰基化反应,制得其6-酰基衍生物4a~4j。用小鼠测试了所合成化合物的抗炎和镇痛活性。结果与结论合成了10个未见文献报道的新化合物4a~4j,其结构经MS1、H-NMR分析确证。抗炎镇痛试验表明,有些化合物具有明显的抗炎和/或镇痛作用,其中化合物4d的活性与对照药布洛芬相当。     

Synthesis of novel 1-pyrazolylpyridin-2-ones as potential anti-inflammatory and analgesic agents

A new series of 4-alkyl/aryl-2-oxo-1-pyrazolyl-1,2-dihydropyridine-3-carbonitriles, pyrazolo[3,4-b]pyridine-5-carbonitriles and pyrido[2,3-d]pyrimidine-6-carbonitriles have been synthesized and tested for their anti-inflammatory and analgesic activities. Among the tested compounds, 3e and 8b exhibited comparable anti-inflammatory activity to the standard (indomethacin). Compounds 5, 7a, and 8b displayed potent analgesic activity. Detailed syntheses, spectroscopic and biological data are reported.     

Synthesis and pharmacological evaluation of some 4-oxo-quinoline-2-carboxylic acid derivatives as anti-inflammatory and analgesic agents

The synthesis and the pharmacological activity of a series of 1-aroyl derivatives of kynurenic acid methyl ester (4-oxo-quinolin-2-carboxy methyl (KYNA) esters), structurally related to NSAID indomethacin are described. The derivatives were screened in vivo for anti-inflammatory and analgesic activities. Most of the compounds exhibited good anti-inflammatory and analgesic activities. An automatic docking of the synthesized compounds was performed using X-ray structures of COX-1 and COX-2. Docking results are in good accordance with the experimental biological data.     

Synthesis, anti-inflammatory and analgesic activity of some new 4(3H)-quinazolinone derivatives

4(3H)-quinazolinone and pyrazole derivatives have been shown to have analgesic and anti-inflammatory properties. In this study, 14 new 3-methyl-4(3H)quinazolinone derivatives bearing 2-[1'-phenyl-3'-(substituted-phenyl)-2'-propenylidene]hydrazino or 2[5'-(substituted phenyl)-3'-phenyl-2'-pyrazolin-1'-yl] groups have been synthesized with the aim of obtaining new analgesic and anti-inflammatory leads. The structures were elucidated by means of UV, IR, 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis data. The anti-inflammatory activities of the synthesized compounds were determined by carrageenan-induced hind paw edema test in mice. All the compounds showed statistically significant effects. For analgesic activity assessment, p-benzoquinone-induced writhing test was applied in mice. The results obtained were in accordance with the anti-inflammatory activity tests.     

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.     

六应丸抗炎和镇痛活性的实验研究

目的：观察六应丸的抗炎和镇痛作用,为其在临床应用提供实验依据。方法：采用醋酸致小鼠扭体模型和热刺激致疼痛模型,考察其镇痛活性;采用二甲苯所致的小鼠耳肿胀和酵母所致大鼠足趾肿胀,考察其抗炎作用,并和六神丸的疗效进行比较。结果：六应丸能有效抑制醋酸引起的小鼠扭体反应、二甲苯所致的小鼠耳肿胀和酵母所致大鼠足趾肿胀,其抗炎镇痛作用与六神丸无显著差异。结论：六应丸具有显著的抗炎镇痛作用。     

A study of anti-inflammatory activity of some novel alpha-amino naphthalene and beta-amino naphthalene derivatives

In the present study, some naphthalene derivatives have been synthesized by incorporating azetidinyl and thiazolidinyl moieties at its alpha- or beta-positions such as alpha-(3-chloro-2-oxo-4-substituted)aryl-1-azetidinyl)naphthalenes 6-10, alpha-((substituted)aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 11-15, beta-(3-chloro-2-oxo-4-substituted aryl-1-azetidinyl)naphthalenes 21-25, and beta-(substituted aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 26-30. These compounds have also been screened for acute toxicity and anti-inflammatory and analgesic activities. Compounds which showed better anti-inflammatory and analgesic activities were also examined for their ulcerogenic liability and underwent a cyclooxygenase assay. Two compounds, 12 and 28, were found to exhibit potent anti-inflammatory activity as compared to the standard drugs phenylbutazone and naproxen.     

Quinoline: A versatile heterocyclic

Quinoline or 1-aza-naphthalene is a weak tertiary base. Quinoline ring has been found to possess antimalarial, anti-bacterial, antifungal, anthelmintic, cardiotonic, anticonvulsant, anti-inflammatory, and analgesic activity. Quinoline not only has a wide range of biological and pharmacological activities but there are several established protocols for the synthesis of this ring. The article aims at highlighting these very diversities of the ring.     

4-Dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol-4-yl)butan-1-ols: synthesis and evaluation of analgesic, anti-inflammatory and platelet anti-aggregating activities

A number of 4-dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol-4-yl)butan-1-ols 2a-n were synthesized and tested in vivo for anti-inflammatory and analgesic activities and in vitro for platelet anti-aggregating activity. Dimethylaminoderivatives 2b, e, g showed good analgesic activity; almost all of them had strong platelet anti-aggregating properties at a final concentration of 1 x 10(-3) M; pyrazoles 2c, d, f-h showed weak anti-inflammatory activity.     

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

Objectives:

Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models.

Materials and Methods:

Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy''s hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg.

Results:

The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg).

Conclusion:

Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract.