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Syntheses of 2,3-Dihydro-1,4-Benzodioxins and Bioisosteres as Structural Motifs for Biologically Active Compounds
Current Organic Chemistry ( IF 2.6 ) Pub Date : 2011-02-28 , DOI: 10.2174/138527211794518925
Olga Cruz-Lopez , Maria C. Nunez , Ana Conejo-Garcia , Maria Kimatrai , Joaquin M. Campos

The 2,3-dihydro-1,4-benzodioxin ring system is present in a large number of structures of therapeutic agents possessing important biological activities. Some of them are antihypertensive agents. Others are involved in nervous breakdown and schizophrenia or represent an attractive therapeutic target for the treatment of glaucoma. The 2,3-dihydro-1,4-benzodioxin core has also been developed for the synthesis of inhibitors of 5-lipoxygenase and accordingly, these 2,3-dihydro-1,4-benzodioxins are useful for the treatment of inflammatory diseases such as asthma and arthritis. The synthesis and reactivity of several bioisosteres of the non-aromatic ring will be discussed. The occurrence of the 2,3-dihydro-1,4-benzodioxin structure in various naturally abundant compounds is also known. The total synthesis of angustureine (a novel 1,2,3,4-tetrahydroquinoline alkaloid with a n-pentyl side chain at position 2) will be presented. The bioisosteric replacement of benzene by pyridine in compounds containing the 2-substituted-2,3-dihydro-1,4-benzodioxin core has yielded derivatives of biological interest in diverse therapeutic areas such as central nervous system and cardiovascular diseases. These promising results have prompted interest in the area of 1,4-dioxino-[2,3-b]pyridine analogues. Several modifications on both the aromatic and the non-aromatic rings will be reviewed, including several transformations of the new heterocycles, such as the Smiles rearrangement. Moreover, the enantiomers of 2- and 3-hydroxymethyl- 2,3-dihydro-1,4-dioxino-[2,3-b]pyridines, important chiral building blocks for the preparation of several biologically active compounds, have been synthesized. We have made an attempt to take into account the largest possible number of original papers, including our research and others. Publications of the last eleven years are included in this review.



中文翻译:

2,3-二氢-1,4-苄二恶英和生物甾体的合成作为生物活性化合物的结构基序。

2,3-二氢-1,4-苯并二恶英环系统存在于许多具有重要生物学活性的治疗剂结构中。其中一些是降压药。其他涉及神经衰弱和精神分裂症或代表青光眼治疗的有吸引力的治疗靶标。还已经开发了2,3-二氢-1,4-苯并二恶英核心以合成5-脂氧合酶的抑制剂,因此,这些2,3-二氢-1,4-苯并二恶英可用于治疗炎症性疾病,例如如哮喘和关节炎。将讨论非芳香环的几种生物等排体的合成和反应性。还已知在各种天然丰富的化合物中存在2,3-二氢-1,4-苯并二恶英结构。总的合成方法(一种新的1,2,3,将介绍在位置2)具有正戊基侧链的4-四氢喹啉生物碱。在含有2-取代的2,3-二氢-1,4-苯并二恶英核心的化合物中,吡啶被吡啶进行生物等位取代,从而在各种治疗领域(如中枢神经系统和心血管疾病)中产生了具有生物学价值的衍生物。这些有希望的结果引起了人们对1,4-二恶英-[2,3-b]吡啶类似物的兴趣。本文将对芳族和非芳族环上的几种修饰进行综述,包括新杂环的几种转化,例如Smiles重排。此外,已经合成了2-和3-羟甲基-2,3-二氢-1,4-二氧杂-[2,3-b]吡啶的对映异构体,它们是制备几种生物活性化合物的重要手性结构单元。我们已尝试考虑尽可能多的原始论文,包括我们的研究和其他论文。该评论包括最近十一年的出版物。

更新日期:2011-02-28
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