棉酚与三氮唑类衍生物的合成及抗菌活性研究

目的:探讨棉酚与三氰唑类衍生物合成工艺的条件及合成物的抗菌活性,反应条件涉及温度、物料比、反应时间及反应溶剂.方法:通过正交设计寻找最佳工艺,运用熔点测定仪、红外、紫外、核磁共振等榆测是否有新物质生成及化学结构,通过TLC监测反应进行程度,用抑菌实验对衍生物的抗菌活性进行研究.结果:棉酚与三氮唑类衍生物合成的最佳工艺的反应温度70℃,反应时间3 h,反应溶剂为无水乙醇,物料比为1:3.结论:生成的衍生物有较强的脂溶性,在优化工艺下进行反应产量较高,为棉酚与三氮唑类衍生物合成提供了较好的方法.     

白桦脂酸衍生物的合成修饰及其抗菌活性研究

目的：设计白桦脂酸（BA）的新型衍生物结构，研究其及衍生物的体外抗菌活性。方法：通过Jones氧化反应、Claisen Schmidt缩合反应等得到目标化合物BA-01；采用96孔板的琼脂稀释法测定化合物对5种细菌的最小抑菌浓度（MIC）。结果：合成了一种具有新型结构的BA衍生物，且为首次报道的新化合物，其结构通过¹H NMR，¹³C NMR和MS（ESI）等表征分析确定。体外抗菌活性测试结果表明，目标化合物对3种革兰阳性菌均有显著的抑菌活性，其中对金黄色葡萄球菌的抑菌活性最高，其最小抑菌浓度（MIC）为12.5 μmol·L^-1，与BA相比显著提高。结论：合成修饰的新型结构中C-3位羟基的修饰以及C-2位上苯环的连接对其生物活性具有重要影响，值得进一步深入探究。     

Synthesis and antibacterial activity of O-methylazithromycin derivatives.

A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1). O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually. Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1. The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity. The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.     

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 antimalarial activity of substituted pyrazole derivatives

The development of new antimalarial drugs is an urgent priority considering the increasing prevalence of drug-resistant Plasmodium falciparum parasites. A series of pyrazoles are described as part of efforts directed toward the synthesis of some potent antimalarial agents. The replacement of the ester group as a substituent in the pyrazole ring by nitrile group caused a precipitous loss of activity as antimalarial due to the lack of hydrogen-bond formation. Further modification of the heterocyclic ring to give substituted aryl derivatives afforded potent antimalarial derivatives: methyl 5-amino-3-anisidinepyrazole-4-carboxylic acid 3a (IC50: 0.149 mumol/l) and methyl 5-amino-3-(m anisidin)pyrazole-4-carboxylic acid 3c (IC50: 0.15 mumol/l). The synthesis, structure-activity relationships (SAR), X-ray crystallography and pharmacological activity associated with these series of compounds are discussed.     

Reactions with maleimides VII: synthesis of several new pyrazolonyl-pyrrolidino[3,4-d]pyrazoline and pyrazolonyl-pyrrolo [3,4-d]pyrazole derivatives

Several new pyrazolonyl-pyrrolidino[3,4-d]pyrazolidines and pyrazolonyl-pyrrolo[3,4-d]pyrazoles were synthesised via the reaction of N-arylmaleimides with the phenylhydrazones of 3-methyl-4-formyl-2-pyrazoline-5-one and 1-phenyl-3-methyl-4-formyl-pyrazolin-5-one and treating of the resulting adducts with chloranil. Structures were based on elemental analyses and spectral data.     

Quinolizidine derivatives with antibacterial activity

Six quinolizidinyl-derivatives were tested for antibacterial actvity against a large number of gram-positive and gram-negative strains. 9-Lupinyliden-fluorene (I) and its epimer (II) at concentrations between 12,5 and 100 mg/l inhibit all gram-positive strains, while they are only weakly active against a few gram-negative bacteria. The tertiary alcohols (III) and (IV) are inactive against the gram-positive strains, while still exhibiting weak activity on the gram-negative. Compounds (V) and (VI) are completely inactive. The values of minimal bactericidal concentrations for compound (I) against the sensitive strains are equal to or no more than 4 times higher than values of MIC. It is interesting to note that compound (I) is able to give rise to cellular lysis at MIC.     

环丙沙星衍生物的合成及抗菌活性研究

目的研究环丙沙星衍生物的合成及其抗菌活性。方法采用2-甲基-5-硝基咪唑、环丙沙星等为原料,通过亲核取代反应合成目的物；测定目的物的抗菌活性。结果设计、合成了9个新化合物,其结构经MS,¹H NMR和元素分析确证。化合物II, IV_C和 IV_D的体内抗菌活性较明显。结论化合物II, IV_C和 IV_D显示了一定的体内抗菌活性,值得进一步研究。     

诺氟沙星衍生物的合成及其抗菌活性研究

目的 设计合成具有抗菌活性的诺氟沙星衍生物。方法 采用2-甲基-5-硝基咪唑、诺氟沙星等为原料，通过亲核取代反应合成目的物；测定目的物的体内抗菌活性。结果 合成的9个化合物的结构经MS、^1H-NMR和元素分析所确证。结论 合成了9个未见报道的新化合物，体内活性测试结果表明：其中的3个化合物具有较高的抗菌活性。     

Non-steroidal antiinflammatory agents, II: Synthesis of novel pyrazole and pyrazoline derivatives of 4(3H)-quinazolinone

Antiinflammatory and/or analgesic activities have been ascribed to compounds containing the 4(3H)-quinazolinone or pyrazole moiety. Continuation to the previous work in the field of the synthesis of non-steroidal antiinflammatory 4(3H)-quinazolinones, the present investigation deals with the synthesis of new compounds having the pyrazole or pyrazoline and 4(3H)-quinazolinone moieties in one molecule, hoping that such combination might improve their antiinflammatory activity. alpha,beta-unsaturated ketones when treated with hydrazine hydrate achieve cyclization to the corresponding pyrazoline derivatives, whereas, when arylhydrazines are used, pyrazole derivatives are formed.     

Antimicrobial activity of new 4,6-disubstituted pyrimidine, pyrazoline, and pyran derivatives

A number of new 2,6-didisubstituted pyrimidine, pyrazoline, and pyran derivatives were synthesized starting from their chalcone derivative. The synthesized compounds displayed different degrees of antimicrobial activity against Bscillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes).     

Pharmacological aspects of pyrazoline derivatives from 2-hydroxy-butenolides.

A series of pyrazoline derivatives was synthetised and evaluated for toxicological and pharmacological effects; analgesic, hypnotic, anti-inflammatory, antipyretic and cardiovascular properties were screened. Tested compounds were found to have a low toxicity; one of them showed a good analgesic activity without side effects.