金刚烷胺衍生物的设计、合成及其抗禽流感病毒活性

目的 设计合成金刚烷胺衍生物并对其进行抗禽流感病毒活性测试。方法 以金刚烷甲酰氯和氨基酸甲酯盐酸盐为起始原料经酰胺化、水解、成盐等反应依次得到3个系列金刚烷胺衍生物。以金刚烷胺为阳性对照,采用幼犬肾（MDCK）细胞系噬斑形成实验测定目标化合物的抗禽流感病毒活性。结果与结论 共合成了20 个未见报道的新化合物,目标化合物的结构均经¹H-NMR、IR、MS 谱确证;仅有化合物 A₅ 显示出较好的抗禽流感病毒活性。     

具抗病毒活性的金刚烷胺衍生物的研究进展

目的 介绍M2离子通道抑制剂金刚烷胺衍生物的研究进展,为设计新的抗流感病毒药物提供相关依据和信息。方法 对近年来关具抗流感病毒活性金刚烷胺衍生物、类似物的相关文献进行综述。结果 国内外课题组主要集中在金刚烷的1位和2位修饰,合成一系列金刚烷胺衍生物或结构类似物,并进行抗流感病毒活性测试。结论 部分金刚烷胺衍生物具有较好的抗流感病毒活性,其中一些化合物的活性优于金刚烷胺和金刚乙胺,这些结果对设计新的抗流感病毒药物具有较好的参考价值。     

新型阿魏酸类衍生物的设计、合成及对LPS诱导N9小胶质细胞激活的抑制作用研究

目的设计合成一系列阿魏酸衍生物并测定其体外抑制LPS激活N9小胶质细胞的活性。方法以香兰素为起始原料,经Knoevenagel反应,与美金刚胺盐酸盐直接缩合得基本母核结构(AMJ),再经Mannich反应得到8个目标化合物。采用建立体外LPS激活N9小胶质细胞异常活化的筛选模型对合成的目标化合物活性进行评价。结果合成了8个未见报道的新化合物,其结构经MS及1H-NMR谱确证。活性实验结果表明,化合物4a⁴g能够显著抑制LPS刺激的N9小胶质细胞NO释放,在其发挥抑制作用的浓度范围内不影响小胶质细胞存活率。结论阿魏酸衍生物可能具有减轻小胶质细胞活化介导的神经系统疾病(如神经退行性疾病)的潜在作用。     

若干莽草酸衍生物的合成和生物活性研究

虽然对莽草酸(shikimic acid)的研究由来已久,但只是在陆续发现了具有生物活性的乙二醛酶Ⅰ抑制剂(glyoxalase Ⅰinhibitor 1)和二(口恶)霉素(dioxolamycin 2)等含莽草酸类母核的天然产物后,才有合成莽草酸衍生物进行生物活性研究的报道,即由莽草酸甲酯合成乙二醛酶Ⅰ抑制剂的类似物3。     

γ－聚谷氨酸衍生物合成研究进展

目的：对γ－聚谷氨酸衍生物的研究背景和合成研究进展展开综述,为γ－聚谷氨酸衍生物的合成提供工作思路。方法通过 CNKI、PUBMED、Elsevier等国内外数据库对相关的近年期刊文献,研究成果进行查阅。结果列出了聚谷氨酸衍生物合成方法中主要的四种方法,并综述了合成产物药理作用。结论四种合成方法为合成新型γ－聚谷氨酸衍生物提供了新的思路。开发新型聚谷氨酸衍生物将在未来的医药行业中具备巨大的发展潜力。     

含氟β-咔啉类衍生物的合成及其生物活性

以色氨酸甲酯盐酸盐、三氟乙酸和三苯基膦为原料，在四氯化碳溶剂中用一锅法在β-咔啉母核中引入三氟甲基，并通过酯的氨解反应合成一系列新型含氟．β-咔啉类衍生物，其结构经IR、MS、^1H—NMR和^13C-NMR确证。初步体外活性实验表明，所合成的化合物具有一定的抗肿瘤活性和对单胺氧化酶的抑制活性。     

章鱼胺衍生物的合成及抗氧化活性研究

目的以章鱼胺为原料合成其衍生物,考察它们的抗氧化活性。方法利用DPPH法对酪胺、章鱼胺及章鱼胺衍生物的抗氧化活性进行测定。结果与结论既往研究指出,章鱼胺的前体化合物酪胺具有较高的抗氧化活性。本研究结果表明,章鱼胺及其两种衍生物具有高于酪胺的抗氧化活性,值得进一步研究。     

酚苄明衍生物的合成及其生物活性

利用酚苄明结构中氯乙胺基的活性，结合一些钙拮抗剂含乙二胺结构的特征，设计合成了５个酚苄明衍生物。初步药理结果表明，所合成的化合物在１０＾－５ｍｏｌ／Ｌ时对高血钾引起的细胞内钙升高具有一定的抑制作用，体外抑制血小板聚集的作用其ＩＣ５０在１０＾－４￣１０＾－５ｍｏｌ／Ｌ。     

苦参碱及其衍生物合成及生物活性研究进展

目的综述苦参碱及其衍生物的最新研究进展。方法通过查阅大量相关文献,对苦参碱及其衍生物的合成和药理活性资料进行整理、分析,并总结了一部分化合物的构效关系。结果与结论大多数苦参碱衍生物在抗肿瘤、抑菌、抗炎镇痛等方面的生物活性都有较大的提高。     

肌肽酯类衍生物的合成与生物活性评价

目的设计并合成10个肌肽酯类衍生物,并评价其清除丙烯醛活性。方法以三甲基氯硅烷为起始原料,以相应的醇作为溶剂和反应物,与肌肽反应得到目标化合物。采用丙烯醛法对目标化合物进行清除丙烯醛活性评价。结果与结论合成了10个肌肽的酯类衍生物,其中7个化合物未见文献报道,目标化合物的结构经1H-NMR、13C-NMR和MS谱确证。活性测试结果表明,目标化合物在1.5 mmol·L-1浓度下对丙烯醛均有一定的抑制作用,其中化合物3a、3i和3j活性最强,清除率分别为71.4%、69.8%和69.8%,与对照药物肌肽(88.0%)相当,具有深入研究的价值。     

新型丹参素衍生物的合成与初步活性研究

目的对丹参素进行结构修饰,改善其理化性质和生物活性。方法以丹参素为母核结构,设计并合成丹参素衍生物。建立叔丁基过氧化氢诱导心肌细胞损伤模型,MTT方法检测丹参素及其衍生物对叔丁基过氧化氢诱导的H9c2细胞损伤的保护作用。结果合成了5个全新丹参素衍生物（2、3、4、7、8）,其化学结构经现代波谱学方法确认。结论丹参素羧基部位进行酯键修饰能明显增加其抗氧化活性,结果优于酰胺键。     

阿齐利特类似物的合成及其抗心律失常活性研究

目的 设计合成阿齐利特类似物,并研究其体外抗心律失常活性。方法 以1-氨基海因盐酸盐(1)为原料,1与一系列醛进行缩合反应得到关键中间体1-(取代甲叉基)氨基海因(2);2与1,4-二溴丁烷或1,3-二溴丙烷反应生成3,3与一系列仲胺反应,再经成盐得到盐酸阿齐利特衍生物。结果 设计合成了未见文献报道的12个目标化合物,所有化合物均经过¹H-NMR谱及MS谱确证。结论 目标化合物5b、5h、5i、5j对离体心肌细胞具有III类抗心律失常药物延长动作电位时程的特征,其中化合物5h活性最好。     

Synthesis and antifertility activity of zoapatanol analogues

The synthesis of and guinea pig contragestational screening data for several oxepane and 3,8-dioxabicyclo[3.2.1]octane analogues of zoapatanol (1) are described and their structure-activity relationships discussed. Conversion of the 5-keto group on the nonenyl side chain of 1 into a hydroxyl function enhanced the potency. Further significant enhancement in the potency was realized with the transformation of several oxepanes into the 3,8-dioxabicyclo-[3.2.1]octane-1-acetic acid derivatives. Detailed, comparative contragestational evaluation of the three most potent compounds 9, 33, and 37 is presented, which led to the selection of 33 (ORF 13811) for further biological evaluation.     

Synthesis and biological activity of sinefungin analogues

A series of nucleosides (2-4) that derive from adenosine by chain extension at the 5'-end have been synthesized starting from the known phosphonate 7. The latter was first combined with 4-pentenal to give 8, which underwent chemical manipulations to provide triacetate 11, which was found suitable for the adenylation step. Further transformations, among them the Hofmann degradation of the amide group of compound 13, and final deprotection gave nucleosides 2-4. They were considered as analogues of sinefungin (1) and tested for their antileishmanial activity together with compounds 5 and 6, which were obtained independently. All the modifications with respect to sinefungin resulted in nearly complete loss of growth inhibitory activity. These results indicate that the 9' terminal amino and carboxyl groups are necessary for the activity and that the presence of the amino group at C-6' is not sufficient to maintain the antileishmanial effect. Some of the analogues however could antagonize or reverse the inhibitory activity of sinefungin (1).     

Synthesis and antiviral activity of helioxanthin analogues

A series of natural product analogues based on helioxanthin (2), with particular attention to modification of the lactone ring and methylenedioxy group, were synthesized and evaluated for their antiviral activities. Among them, lactam derivative 18 and helioxanthin cyclic hydrazide 28 exhibited significant in vitro antiviral activity against hepatitis B virus (EC(50) = 0.08 and 0.03 microM, respectively). Compound 18 showed the most potent antiviral activity against hepatitis C virus (55% inhibition at 1.0 microM). Compound 12, an acid-hydrolyzed product of helioxanthin cyclic imide derivative 9, was found to exhibit broad-spectrum antiviral activity against hepatitis B virus (EC(50) = 0.8 microM), herpes simplex virus type 1 (EC(50) = 0.15 microM) and type 2 (EC(50) < 0.1 microM), Epstein-Barr virus (EC(50) = 9.0 microM), and cytomegalovirus (EC(50) = 0.45 microM). Helioxanthin lactam derivative 18 also showed marked inhibition of herpes simplex virus type 1 (EC(50) = 0.29 microM) and type 2 (EC(50) = 0.16 microM). The cyclic hydrazide derivative of helioxanthin 28 and its brominated product 42 exhibited moderately potent activities against human immunodeficiency virus (EC(50) = 2.7 and 2.5 microM, respectively). Collectively, these molecules represent a novel set of antiviral compounds with unique structural features.     

Synthesis and cytostatic activity of geiparvarin analogues

In an attempt to determine some of the structural features of geiparvarin (1) that account for its cytostatic activity in vitro, a series of geiparvarin analogues (4a-g) modified in the 3(2H)-furanone moiety have been designed and synthesized. The preparation of 4a-g was achieved through a new approach to the 3(2H)-furanone ring based on the elaboration of isoxazole derivatives. Among these synthetic analogues, 4b, the 5-methyl-5-ethyl derivative, proved as active as 1 in inhibiting the proliferation of murine and human tumor cell lines in vitro. As a rule, substitutions at the C5 atom of the 3(2H)-furanone moiety of 1 slightly decreased the cytostatic activity of geiparvarin. Several geiparvarin analogues described in this study (i.e. the 5-methyl-5-ethyl derivative 4b, 3(2H)-furanimine 4c, 5-methyl derivative 4f, and 5-ethyl derivative 4g) showed such activity in vitro and deserve further investigation for their antitumor potentials in vivo.     

Synthesis and evaluation of neuroprotective alpha,beta-unsaturated aldehyde scavenger histidyl-containing analogues of carnosine

The synthesis, scavenging activity, and cytoprotective profiles of histidyl-containing carnosine analogues bearing hydrazide or 1,2-diol moieties is reported. Some compounds have demonstrated higher aldehyde-sequestering efficiency than carnosine and were also efficient in protecting SH-SY5Y neuroblastoma cells and rat hippocampal neurons from 4-hydroxy-trans-2,3-nonenal (HNE)-mediated death. The cytoprotective efficacy of these compounds suggests their potential use as therapeutic agents for disorders that involve excessive membrane lipids peroxidation and HNE-mediated neuronal toxicity.     

Antiviral activity of uridine 5'-diphosphate glucose analogues against some enveloped viruses in cell culture

Twenty five analogues of uridine 5'-diphosphate glucose were screened against herpes simplex type 2, vaccinia virus, Sindbis virus and African swine fever virus. After screening, the compound 5'-[[[[(2",3",4",6"-tetra-O-benzoyl-alpha-D- glucopyranosyl)oxi]carbonyl]amino]sulfonyl]uridine (2), the synthesis of which has been reported (Camarasa et al., J. Med. Chem. 28, 40-46, 1985), was selected for further study. This compound showed in vitro activity against all viruses tested. The replication of herpes virus type 2 and African swine fever virus was completely inhibited at 100 micrograms/ml and 150 micrograms/ml respectively; vaccinia virus and Sindbis virus were inhibited to a lesser extent. The compound may inhibit several steps in the viral replication process.