6-amino-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7H-purine-8-thione

• 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: 6-amino-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7H-purine-8-thione
• 化学式: C₁₀H₁₃N₅O₄S
• 分子量: 299.31
• InChiKey: QILZVYQRHGBEAR-VKJDSPIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  8

文献信息

• Derivatives of (hetero) aromatic ethers and thioethers having antihyperlipidemic activity, process for their preparation and pharmaceutical compositions containing them
  申请人：PIERREL S.p.A.

  公开号：EP0520552A1

  公开（公告）日：1992-12-30

  The novel derivatives of (hetero)aromatic ethers and thioethers represented by the following general formula I:         (HET)Ar-X-CH₂-Y-CH₂-O-R   (I) wherein: (HET)Ar represent a mono-,bi- and tri-cyclic aryl or hetero aryl nucleous possibly substituted, X represents -O- or -S-; Y represents -CO-, a linear or branched polymethylene having 0 to 8 carbon atoms with the proviso that it is not (CH₂)n in which 0

  以下是一般公式 I 所表示的 (杂)芳香醚和硫醚的新型衍生物：          (HET)Ar-X-CH₂-Y-CH₂-O-R         (I) 其中： (HET)Ar 表示可能带有取代基的单环、双环和三环芳基或杂芳基核； X 代表 -O- 或 -S-； Y 代表 -CO-，具有 0 到 8 个碳原子的直链或支链聚亚甲基，条件是当 (HET)Ar 表示可能用甲基和/或硝基取代的咪唑环，并且同时 X = S，-CH(OR₁)，其中 R₁ 是氢或来自脂肪族、芳香族或杂环羧酸的酰基，条件是当 (HET)Ar 表示鸟嘌呤、腺嘌呤或腺苷基团时，R₁ 不是氢，-C=N-R₂，其中 R₂ 是氢或具有 1 到 10 个碳原子的直链或支链烷基，OH，具有 1 到 10 个碳原子的烷氧基，芳氧基，芳烷氧基，-NH₂，-NHCONH₂，-NHCSNH₂；且 R 代表在间位带有羧基或 (C₁-C₂0) 烷氧甲酸基的苯基，其中烷氧基可以是直链或支链的，具有抗高脂血症活性。 此外，还描述了它们的制备过程和含有它们的药物组合物。
• C8-substituted purine nucleotide analogs and their use as inhibitors of nucleoside triphosphate diphosphohydrolases
  申请人：——

  公开号：US20040043955A1

  公开（公告）日：2004-03-04

  Ectonucleoside triphosphate diphosphohydrolases [NTPDases; EC 3.6.1.5] constitute a family of enzymes which are involved in the metabolism of extracellular nucleotides, catalysing the hydrolysis of the gamma and beta phosphate bonds of triphospho- and diphosphonucleosides (whereas 5′nucleotidases [EC 3.1.3.5] catalyse the hydrolysis of alpha phosphate bond of monophosphonucleosides). These extracellular nucleotides interact with endothelial, epithelial and smooth muscle cells, as well as blood cells and lymphoid cells, to influence the different physiological systems of vertebrates. Since these ecto-nucleotidases alter the extracellular concentrations of nucleotides these enzymes modulate their physiological effects, including, for example, platelet aggregation, heart function, control of vascular tone and inflammation reactions, electrolyte secretion and gastrointestinal motility, neurotransmission both in central and peripheral nervous systems, as well as other effects in other physiological systems. This invention provides C8 substituted purine nucleotide analogues, such as ATP analogues, and further provides their use as inhibitors of NTPDases and thereby as tools to modulate the conversion of nucleotides into nucleoside derivatives, and thus modulate the levels of these compounds. Such modulation further provides for the modulation of the activity and function of many processes which are affected by these compounds.

  外核苷酸三磷酸二氢酶（NTPDases [EC 3.6.1.5]）是参与细胞外核苷酸代谢的酶家族，催化水解三磷酸和二磷酸核苷的γ和β磷酸键（而 5′核苷酸酶 [EC3.1.3.5]催化水解单磷酸核苷的α磷酸键）。1.3.5]催化水解单磷核苷的 alpha 磷酸键）。这些细胞外核苷酸与内皮细胞、上皮细胞、平滑肌细胞以及血细胞和淋巴细胞相互作用，影响脊椎动物的不同生理系统。由于这些外核苷酸酶会改变核苷酸的细胞外浓度，因此这些酶会调节核苷酸的生理效应，包括血小板聚集、心脏功能、血管张力和炎症反应的控制、电解质分泌和胃肠道蠕动、中枢神经系统和周围神经系统的神经传递，以及对其他生理系统的其他效应。本发明提供了 C8 取代的嘌呤核苷酸类似物，如 ATP 类似物，并进一步提供了它们作为 NTPD 酶抑制剂的用途，从而作为调节核苷酸转化为核苷衍生物的工具，进而调节这些化合物的水平。这种调节作用还可进一步调节受这些化合物影响的许多过程的活性和功能。
• New 8-substituted nucleoside and purine derivatives, the process for the preparation thereof and the pharmaceutical compositions containing them
  申请人：Pierrel S.p.A.

  公开号：EP0175325B1

  公开（公告）日：1989-03-15
• US4774325A
  申请人：——

  公开号：US4774325A

  公开（公告）日：1988-09-27
• US5470858A
  申请人：——

  公开号：US5470858A

  公开（公告）日：1995-11-28