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首页> 外文学位 >Part I. Synthesis of N-substituted 2,5-bis-[4-guanidinophenyl]thiophenes as potential antileishmanial compunds. Part II. Synthesis of novel potential prodrugs of bis-guanidino and bis-amidino molecules.
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Part I. Synthesis of N-substituted 2,5-bis-[4-guanidinophenyl]thiophenes as potential antileishmanial compunds. Part II. Synthesis of novel potential prodrugs of bis-guanidino and bis-amidino molecules.

机译：第一部分：N-取代的2,5-双-[4-胍基苯基]噻吩的合成作为潜在的抗衰老化合物。第二部分双胍基和双-基分子的新型潜在前药的合成。

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摘要

Leishmaniasis is a disease caused by several species of Leishmania which are associated with three clinically different manifestations of the disease: cutaneous, mucocutaneous, and visceral. The regions where leishmaniasis is endemic have expanded significantly and large population movements are fuelling a growing epidemic. More recently, co-infections of HIV and leishmaniasis are becoming more common. The interaction of the two diseases makes each more destructive, accelerating the onset of AIDS and shortening the life expectancy of HIV-infected people. Dealing with evolving infectious diseases requires development of new therapeutic agents.; Aromatic dicationic molecules have shown activity against a variety of animal models for opportunistic infections when given by intravenous infusion (e.g. Pneumocystis carinii). However, the activity of these compounds is significantly less on oral administration. With this promising background, we began to synthesize potential drugs in the guanidine family. The novel guanidino compounds have a furan or a thiophene central ring linked in a symmetrical way (positions 2 and 5) to a phenyl ring which contains the guanidino moiety. The structure of the cationic centers was modified by N-alkyl and N-aryl substitution. The new diguanidino compounds were evaluated for their activities against Leishmania and Trypanosomes. Thermal melting studies were performed to examine their binding affinity to nucleic acids by the Wilson laboratory.; Since the oral bioavailability of these dicationic potential drugs is expected to be low, a prodrug approach was used to attempt to enhance bioavailability of these type of compounds. The guanidino moiety was modified in three different ways. Single (carbamates), double (N-methoxy), and triple (a combination of carbamate and N-methoxy) potential prodrugs were synthesized. In an effort to develop new prodrugs for the amidine functional group, 4,5-dihydro-3,5-disubstituted-1,2,4-oxadiazoles analogs of furamidine were also synthesized.
机译：利什曼病是由几种 Leishmania 引起的疾病，与三种临床上不同的疾病表现有关：皮肤，粘膜皮肤和内脏。利什曼病流行的地区已大大扩大，人口的大量流动加剧了这一流行病的流行。最近，HIV和利什曼病的合并感染变得越来越普遍。两种疾病的相互作用使每种疾病更具破坏性，加速了艾滋病的发作，并缩短了艾滋病毒感染者的预期寿命。应对不断发展的传染病需要开发新的治疗剂。当通过静脉内输注（例如卡氏肺孢子虫）给予时，芳香性双能分子已表现出针对多种机会性感染动物模型的活性。然而，这些化合物的活性在口服给药时明显降低。在这种有希望的背景下，我们开始合成胍家族中的潜在药物。新的胍基化合物具有呋喃或噻吩中心环，该环以对称方式（位置2和5）连接至包含胍基部分的苯环。通过 N -烷基和 N -芳基取代修饰阳离子中心的结构。评价了新的双胍化合物对利什曼原虫和锥虫的活性。威尔逊实验室进行了热熔研究，以检查它们与核酸的结合亲和力。由于预期这些潜在的潜在药物的口服生物利用度较低，因此使用前药方法尝试增强这些类型化合物的生物利用度。胍基部分以三种不同方式被修饰。合成了单（氨基甲酸酯），双（ N -甲氧基）和三（氨基甲酸酯和 N -甲氧基的组合）潜在前药。为了开发用于am官能团的新前药，还合成了呋喃啶的4，5-二氢-3，5-二取代-1，2，4-恶二唑类似物。

著录项

  • 作者

    Gonzalez-Roman, Jose Luis.;

  • 作者单位

    Georgia State University.;

  • 授予单位 Georgia State University.;
  • 学科 Chemistry Organic.; Chemistry Pharmaceutical.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 p.5849
  • 总页数 125
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 有机化学;
  • 关键词

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