N⁶-methyl-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)adenine | 85326-07-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-methyl-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)adenine
• 英文别名: N⁶-methyl-2',3'-dideoxyadenosine；6-methyl-2',3'-dideoxyadenosine；[(2S,5R)-5-[6-(methylamino)purin-9-yl]oxolan-2-yl]methanol
• CAS: 85326-07-4
• 化学式: C₁₁H₁₅N₅O₂
• 分子量: 249.272
• InChiKey: ODPGJSIBNBRBDT-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  85.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N⁶-benzoyl-N⁶-methyl-5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-<(methylthio)thiocarbonyl>adenosine 在 palladium on activated charcoal 偶氮二异丁腈 、 四丁基氟化铵 、 氨 、 氢气 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 乙醇 、 水 、 苯 为溶剂， 25.0 ℃ 、379.21 kPa 条件下， 反应 30.75h， 生成 N⁶-methyl-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)adenine
  参考文献：
  名称：

  6-取代的2'，3'-二脱氧嘌呤核苷作为潜在的抗人免疫缺陷病毒制剂的合成与构效关系。

  摘要：

  为了研究2'，3'-二脱氧嘌呤核苷作为潜在的抗HIV药物的构效关系，已经合成了多种6-取代的嘌呤类似物，并在病毒感染和未感染的人外周血单核细胞中进行了研究。N6-甲基-2'，3'-二脱氧腺苷（D2MeA，7a）最初是通过2'，3'-O-双黄药3由腺苷合成的。由于该反应扩展到其他N6-取代的化合物失败，因此采用了全合成方法利用2'，3'-二脱氧核糖衍生物9合成其他嘌呤核苷。通过与N6-甲基腺嘌呤23缩合，由合适的碳水化合物24合成了N6-甲基-2'，3'-二脱氧腺苷，2'-氟阿拉伯呋喃糖基类似物32（D2MeFA）的酸稳定衍生物。N6-甲基衍生物（D2MeA）7a被证明是最有效的抗病毒药物之一。对于6个取代的化合物，其效力顺序为NHMe大于NH2大于Cl约N（Me）2大于SMe大于OH约NHEt大于SH大于NHBn约H。 2'，3'-二脱氧嘌呤核苷的6位可能决定这些化合物的抗病毒活性。发现酸

  DOI：

  10.1021/jm00168a006

文献信息

• [EN] NEW ANTI-MYCOBACTERIAL DRUGS AGAINST TUBERCULOSIS<br/>[FR] NOUVEAUX MÉDICAMENTS ANTI-MYCOBACTÉRIENS CONTRE LA TUBERCULOSE
  申请人：UNIV GEORGIA

  公开号：WO2013148174A1

  公开（公告）日：2013-10-03

  The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

  本发明涉及抗结核治疗领域，特别是肺部多药耐药结核病（MDR-TB）的治疗，包括广泛耐药结核病（XDR-TB）和极度耐药结核病（XXDR-TB），优选采用联合治疗。
• Pyridinone Diketo Acids: Inhibitors of HIV Replication in Combination Therapy
  申请人：Nair Vasu

  公开号：US20100092427A1

  公开（公告）日：2010-04-15

  A new class of diketo acids constructed on pyridinone scaffolds, designed as inhibitors of HTV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described. Compounds of the present application include those of formula I and include tautomers, regioisomers, geometric isomers, and pharmaceutically acceptable salts thereof, wherein the pyridinone scaffold and R groups are as otherwise defined in the specification. These are combined, with any number of typical other anti-HIV agents (including other integrase-based anti-HIV agents) and other combination therapeutic agents described herein, to provide an effective treatment modality for HIV infections, including AIDS and ARC.

  本文描述了一类新型的二酮酸，构建在吡啶酮支架上，设计用于通过抑制HIV整合酶来抑制HIV复制。这些化合物可用于预防或治疗HIV感染以及治疗AIDS和ARC，可以作为化合物本身或与药物载体结合使用，或与其他抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗剂联合使用，尤其是其他抗HIV化合物（包括其他抗HIV整合酶剂），以形成联合抗HIV药物组合。本申请的化合物包括公式I中的化合物和其中的互变异构体、区域异构体、几何异构体和其药学上可接受的盐，其中吡啶酮支架和R基在规范中另有定义。这些化合物与任意数量的典型其他抗HIV药物（包括其他基于整合酶的抗HIV药物）和其他联合治疗剂联合使用，提供了一种有效的治疗HIV感染的治疗模式，包括AIDS和ARC的治疗方法。
• PYRIDINONE HYDROXYCYCLOPENTYL CARBOXAMIDES: HIV INTEGRASE INHIBITORS WITH THERAPEUTIC APPLICATIONS
  申请人：Nair Vasu

  公开号：US20120282218A1

  公开（公告）日：2012-11-08

  New chiral and achiral oxy-substituted cyclopentyl pyridinone diketocarboxamides and their derivatives and methods for their preparations are disclosed. The compounds include tautomers, regioisomers and geometric isomers. These complex carboxamides are designed as inhibitors of HIV replication through inhibition of HIV integrase. The compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

  本发明公开了新的手性和非手性氧取代的环戊基吡啶酮二酮羧酰胺及其衍生物的制备方法。这些化合物包括互变异构体、区域异构体和几何异构体。这些复杂的羧酰胺被设计为通过抑制HIV整合酶来抑制HIV复制的抑制剂。这些化合物可用于预防或治疗HIV感染以及治疗艾滋病和ARC，可以作为化合物或药学上可接受的盐，与药学上可接受的载体一起使用，单独使用或与抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗剂（尤其是其他抗HIV化合物，包括其他抗HIV整合酶剂）组合使用，以创建组合抗HIV鸡尾酒。还描述了治疗艾滋病和ARC以及治疗或预防HIV感染的方法。
• NEW ANTI-MYCOBACTERIAL DRUGS AGAINST TUBERCULOSIS
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：US20150050237A1

  公开（公告）日：2015-02-19

  The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

  本发明涉及抗结核菌治疗领域，特别是肺部多药耐药结核病（MDR-TB）的治疗，包括广泛耐药结核病（XDR-TB）和极度耐药结核病（XXDR-TB），优选采用联合治疗方法。
• Plant deoxyribonucleoside kinase enzymes and their use
  申请人：Knecht Wolfgang

  公开号：US20060230467A1

  公开（公告）日：2006-10-12

  This invention relates to pharmaceutical compositions comprising plant deoxyribonucleoside kinase enzymes (dNK) capable of phosphorylating nucleoside analogs and to medical use of said dNKs. More specifically the invention relates to the medical use of deoxyribonucleoside kinase enzymes derived from ( Arabidopsis thaliana ), from loblolly pine ( Pinus taeda ), from tomato ( Lycopersicum esculentum ), from maize ( Zea mays ) or from rice ( Oryza sativa ). The invention also relates to methods of sensitising cells to prodrugs, and to methods of inhibiting pathogenic agents in warm-blooded animals using said plant dNKs. In another aspect the invention relates to plant derived deoxyribonucleoside kinase enzymes provided in isolated form from loblolly pine ( Pinus taeda ), from tomato ( Lycopersicum esculentum ), from maize ( Zea mays ) or from rice ( Oryza sativa ). In further aspects the invention provides polynucleotides encoding the plant dNKs, vector constructs comprising the polynucleotide, packaging cell lines capable of producing said vector, and genetically modified isolated host cells transduced/transfected/-transformed with the vector.

  本发明涉及包含能使核苷类似物磷酸化的植物脱氧核苷激酶（dNK）的药物组合物，以及所述 dNK 的医学用途。更具体地说，本发明涉及源自( 拟南芥 )、龙柏( 太田松 )、番茄( 番茄 ）、玉米（Zea mays 玉米 ）或水稻（Oryza sativa Oryza sativa ).本发明还涉及使细胞对原药敏感的方法，以及使用所述植物 dNK 抑制温血动物中病原体的方法。 在另一个方面，本发明涉及植物衍生的脱氧核苷激酶，它以分离形式提供自小叶松( 太田松 )、番茄( Lycopersicum esculentum )、玉米( 玉米 ）或水稻（Oryza sativa Oryza sativa ).在进一步的方面，本发明提供了编码植物 dNKs 的多核苷酸、包含多核苷酸的载体构建体、能够产生所述载体的包装细胞系，以及用载体转导/转染/转化的转基因分离宿主细胞。