Synthesis and evaluation of 3 -nitro -2H- chromene derivatives as new antibacterials

目的 设计并合成一系列3-硝基-2H-色烯衍生物,研究其抗菌活性与构效关系.方法 以水杨醛和2-硝基乙醇为原料合成目标化合物,采用肉汤稀释法测定抗菌活性.结果 目标化合物结构均经过1HNMR和HRMS确证,3-硝基-2H -色烯衍生物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌具有很好的抑制活性(MIC =4 μg·mL-1).结论 3-硝基-2H-色烯衍生物具有进一步深入研究的价值.     

N-取代苯基-5-取代苯基-3H-1,2,4-三唑-3-硫酮衍生物的合成及抗菌活性研究

目的 以苯甲酸为原料,经4步反应合成一系列N-取代苯基-5-取代苯基-3H-1,2,4-三氮唑-3-硫酮化合物并研究其抗菌活性。方法 基于课题组前期对新型潜在三唑类抗菌化合物6h的作用机制研究,筛选多个侧链基团,使用乙醇和碳酸钠作溶剂改善最后一步反应条件,通过硅胶柱色谱分离纯化目标化合物,合成一系列1,2,4-三唑类化合物并采用质谱(MS)和1H NMR、13C NMR进行结构表征。通过琼脂扩散法初步筛选所有化合物对肺炎克雷伯菌、金黄色葡萄球菌和铜绿假单胞菌3种常见菌株的抗菌活性,并通过微量稀释法进一步测定它们的最小抑菌浓度(MIC值)。结果 合成17个含有卤代苯基和其他侧链基团的目标化合物,其MS以及核磁共振谱图数据表明所有化合物结构正确。抗菌活性初步筛选可知化合物6a、6b、6d、6f、6g、6h、6k、6m和6p等9个化合物具有不错的抑菌能力,其MIC测试结果表明,大部分化合物对所测菌株的MIC值在25~100μg/mL范围内。尤其是化合物6h和6k对肺炎克雷伯菌的MIC值达到25μg/mL,抑菌活性与对照药物氨苄西林相当。结论 在前期作用机制研究基础上,通过对构效关系的阐述,发现一些侧链片段如间位卤代苯基或对位卤代苯基、三氟甲基苯基等具有吸电子基团的苯基、吡啶基等对1,2,4-三唑类衍生物的抗菌活性有明显增强作用,证实侧链基团与受体蛋白形成特异性协调作用和氢键作用从而发挥衍生物的抗菌活性。     

2H-1-苯并吡喃衍生物的合成及其体外抗癌活性的初步评价

目的设计并合成2H-1-苯并吡喃衍生物化合库并对其体外抗癌活性进行评价。方法以2＇-羟基查耳酮为原料通过微波促进合成得到黄酮衍生物中间体，此中间体与POCl，反应得到4-氯-2H-色原烯-3-醛，通过微波辅助液相平行合成的方法，此醛与ROCONHNH2反应得到2H-1-苯并吡喃衍生物化合库。利用HL-60细胞系评价该化合物库的体外抗癌活性。结果与结论合成了含有32个化合物的2H-1-苯并吡喃衍生物库，体外活性评价表明。部分化合物对HL-60细胞的增殖有一定的抑制作用，其中。化合物9e在浓度为30μmol·L^-1的抑制率为70．8％。     

新红霉素衍生物结构修饰与抗菌活性研究进展

综述了近年来红霉素衍生物的结构修饰与抗菌活性关系研究的最新进展,结果显示,该红霉素类衍生物新药品种具有组织和血药浓度高,半衰期长和抗耐药菌等药代动力学新特性。     

抗菌活性红霉素衍生物研究进展

目的综述具有抗菌活性红霉素衍生物的研究进展。方法依据国内外近期公开发表的53篇文献,对具有抗菌活性红霉素衍生物的研究进展进行分类、归纳与总结。结果长期以来,红霉素及其衍生物作为抗菌药物被广泛使用。20世纪80年代后期问世的第二代大环内酯类抗生素,具有药代动力学性质好、毒性及不良反应小的特点,现已广泛应用于临床。目前,红霉素化学修饰研究的主要目标是研制对大环内酯耐药菌有效的第三代大环内酯类药物。结论利用具有抗菌活性红霉素衍生物研制开发新药,已逐步成为红霉素衍生物研究的重要内容,呈现良好的发展势头。     

2-咪唑基-戊-1,4-二烯-3-酮类衍生物的合成及其抗菌活性研究

目的设计合成2-咪唑基-戊-1,4-二烯-3-酮类衍生物,并进行抗菌活性测试。方法以不同取代的苯甲醛为起始原料,经过Aldol缩合、溴代、亲核取代和Knoevenagel缩合四步反应合成目标化合物;采用微量稀释法测定化合物最低抑菌浓度(MIC)值。结果合成了30个未见文献报道的新化合物,其结构均经1H-NMR、MS谱测定。结论目标化合物均表现出一定的抗菌活性,可作为先导化合物做进一步改造和修饰。     

红霉素衍生物抗菌活性构效关系研究进展

为解决抗生素的耐药性问题，近年来在红霉素化学结构修饰方面开展了大量的研究，并发现了诸如酮内酯、酰内酯、双环内酯等多种具有良好抗耐药菌活性的新型大环内酯类化合物。该文对红霉素衍生物抗菌活性研究成果做一概括，并对构效关系研究的某些重要结论加以探讨。     

前列腺癌显像剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯的合成

目的制备前列腺癌显像剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯的前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐;用前体和放射性核素~(18)F合成~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯。方法以2-羟基-1-乙氧基-3-醛基苯为起始原料,经烯化、环化、磺化、成盐反应得到标记前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐;然后与放射性核素~(18)F经亲核氟代反应,得到~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯。标记前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐及各步反应中间体的结构均经核磁共振谱和质谱确证。结果与结论成功合成前列腺癌诊断显影剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯,标记率为(25.8±2.6)%(n=5,未经衰减校正),TLC测定其放化纯度(RCP)为97.5%,为进一步临床研究奠定了基础。     

非抗菌活性红霉素衍生物研究进展

目的综述非抗菌活性红霉素衍生物的研究进展。方法依据国内外近期公开发表的40篇文献,对非抗菌活性红霉素衍生物的研究进展进行分类、归纳与总结。结果长期以来,红霉素及其衍生物作为抗菌药物被广泛使用。在临床实践中人们发现,该类化合物还具有一些新的生物活性,例如促进消化道运动、抗炎/免疫调节、抗寄生虫、抗肿瘤、拮抗黄体生成素释放激素、以及抑制磷酸二酯酶-3等活性。为提高新活性降低其抗菌作用,已经设计、合成了多种类型的新结构红霉素衍生物。结论利用红霉素衍生物的新活性研制、开发新药已经成为研究热点。     

3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的3位羟基红霉素衍生物。方法　以红霉素A为原料,经9位酮基肟化,9位肟羟基,2′位羟基和3′位二甲胺基同时苄基化,6位羟基甲基化,水解去3位克拉定糖,氢化还原脱苄基,对甲基苄基或邻氯苄基取代9位肟羟基等6步反应,制得3-羟基-6-O-甲基红霉素-9-肟基衍生物,其结构经¹³CNMR ,FAB MS确证。结果　共制得7个化合物,对其中4个(5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　5 ,7,8对部分红霉素诱导耐药菌有一定的活性     

Synthesis, antihypertensive activity, and 3D-QSAR studies of some new p-hydroxybenzohydrazide derivatives

p-Hydroxybenzohydrazide 2 on treatment with aromatic/aliphatic aldehyde followed by cyclization with carbon disulphide afforded compounds 4a-4n. Also, compound 2 by treatment of substituted isothiocyanate followed by the treatment of chloroacetic acid yields the corresponding compounds 6a-6i. All the test compounds were assayed for antihypertensive activity by non-invasive blood pressure measurement and invasive blood pressure measurement methods. The test compounds showed significant antihypertensive activity. The intact compounds were subjected to 3D-QSAR studies. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r(2) = 0.98, q(2) = 0.74) was achieved. The 3D-QSAR plots illustrated insights into the structure-activity relationship of these compounds which may aid in the design of potent p-hydroxybenzohydrazide derivatives as antihypertensive agents.     

Synthesis of new hydantoin-3-ethanethiol derivatives

5-sec-Butylthiomethyl-5-alkyl (methyl or phenyl) hydantoins (3−x) were prepared by the reaction of sec-butylthiomethyl alkyl (methyl or phenyl) ketone (1–2), potassium cyanide and ammonium carbonate. 3-(2-Bromoethyl) hydantoins (5–6) were the reaction products of 5-sec-butylthiomethyl-5-alkyl (methyl or phenyl) hydantoin and 1,2-dibromoethane in the presence of potassium hydroxide. Alkylation of5 and6 with an excess of alkyl (methyl or ethyl) iodide in THF with sodium hydride as base gave three 1-alkyl (methyl or ethyl)-3-(2-bromoethyl) hydantoins (7–9). Treatment of the 2-bromoethyl group with potassium thioacetate and triethylamine gave three 1-alkyl (methyl or ethyl)-3-(2-acetylthioethyl) hydantoins (10–12). Hydrolysis of the 2-acetylthioethyl group with sodium hydroxide in methanol afforded the three 1-alkyl (methyl or ethyl)-3-(2-mercaptoethyl) hydantoins.     

Synthesis and antibacterial evaluation of 1beta-methyl-2-(5-substituted heterocyclic carbamoyl)pyrrolidin-3-ylthio)carbapenem derivatives

The synthesis of a new series of 1beta-methylcarbapenems having a substituted heterocyclic carbamoyl pyrrolidine moiety is described. Their in vitro antibacterial activity against both gram-positive and gram-negative bacteria was tested, and the effect of heterocyclic substituents on the pyrrolidine was investigated. One particular compound (III(d)) having a substituted oxadiazole moiety showed the most potent antibacterial activity.     

Synthesis and antibacterial activity of new 7-piperazinyl-quinolones containing a functionalized 2-(furan-3-yl)ethyl moiety

A number of 7-piperazinylquinolones carrying a functionalized 2-(furan-3-yl)ethyl moiety attached to the piperazine ring have been synthesized and evaluated as antibacterial agents against a panel of Gram-positive and Gram-negative bacteria. Most of the synthesized compounds exhibited significant antibacterial activity, and this activity can be modulated through the nature of the functionality on ethyl spacer attached to piperazine ring and the type of side chain present at the N-1 position of quinolone ring.     

7-[(2S)-2-氨甲基-1-吡咯烷基]-喹诺酮衍生物的合成及体外抗菌活性

为寻找具有广谱抗菌活性的新喹诺酮类化合物，本文以L-脯氨酸为原料，经甲酯化，苄基(Bz)保护，氨解，LiAlH4还原，叔丁氧羰基(BOC)保护，脱苄基，然后与不同的喹诺酮母环化合物缩合。最后脱去叔丁氧羰基等8步反应制得目标化合物，其结构经。H-NMR，FAB-MS确证。本文共制得16个化合物，对其中5个(13～17)目标化合物进行体外抗菌活性测定的结果表明，化合物15对肺炎链球菌的体外活性相当于对照药加替沙星而优于环丙沙星，对其余菌株的活性总体上看则低于对照品。其余4个目标化合物总体上看其活性均低于对照品，甚至基本无活性。     

苯并噁嗪利福霉素衍生物的合成及其抗菌活性初探

目的 设计合成苯并噁嗪利福霉素衍生物，并研究其抗菌活性。方法 以利福霉素S为原料合成目标化合物，并测定其抗菌活性。结果 初步的抗菌活性研究表明：合成的新化合物均有抗菌作用，但其抗菌活性低于对照品。结论 3′-苯并噁嗪酚利福霉素的3′位酚羟基醚化对抗菌活性有影响。     

Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents

Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4–11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12 h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24 h post-administration at tested anti-inflammatory doses. In addition, LD₅₀ for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.     

7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究

目的 寻找新的喹诺酮类抗菌药.方法 设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物,测定其体外抗菌活性.结果 化合物10对金葡菌(包括MRSA)和表葡菌(包括MRSE)的活性(MIC:0.06～4μg/mL)与左氧氟沙星和吉米沙星基本相当.化合物11对肺炎链球菌08-2的活性(MIC:0.25μg/mL)分别是左氧氟沙星和吉米沙星的128倍和32倍,化合物12对肺炎克雷伯菌09-22和09-23的活性(MIC:1μg/mL)分别是左氧氟沙星和吉米沙星的16倍和4倍,但目标物对革兰阴性菌的活性普遍弱于对照药.结论 7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素.     

Synthesis and antioxidant activity of new tetrahydro-naphthalene-indole derivatives as retinoid and melatonin analogs

A number of retinoid-related compounds represent classes of antioxidative and proapoptotic agents with promising potential in the treatment of neoplastic diseases. Indeed, the synthetic retinoid amide fenretinide [N-(4-hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts as a chemotherapeutic drug in cancer therapy. In the present work, and as a continuation of our studies on retinoid-type compounds, the synthesis of melatonin retinamide derivatives was studied as a novel series of melatonin retinoids, using the condensation reaction sequence involving tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin-type moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized compounds, some of them showed a strong inhibition on lipid peroxidation (IVa-b, Va, and VIIa-c, 88, 96, 90, 94, 93, and 86%, respectively at 10(-4) M concentration) when melatonin (85% at 10(-4) M concentration) was used as a reference compound.