3-(1-benzyl-6-oxo-1,6-dihydropurin-9-yl)-N-(3-morpholin-4-yl)propyl propionamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 3-(1-benzyl-6-oxo-1,6-dihydropurin-9-yl)-N-(3-morpholin-4-yl)propyl propionamide
• 英文别名: 3-(1-Benzyl-6-oxo-1,6-dihydropurin-9-yl)-N-(3-morpholin-4-yl-propyl)Propionamide；3-(1-benzyl-6-oxopurin-9-yl)-N-(3-morpholin-4-ylpropyl)propanamide
• 化学式: C₂₂H₂₈N₆O₃
• 分子量: 424.503
• InChiKey: OQCDWECCWBEWGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(3-氨丙基)吗啉 、 3-(1-benzyl-6-oxo-1,6-dihydropurin-9-yl) propionic acid methyl ester 在 乙腈 作用下， 以 乙腈 为溶剂， 反应 3.5h， 以resulting in 200 mg (34%) of the title compound as a white solid的产率得到3-(1-benzyl-6-oxo-1,6-dihydropurin-9-yl)-N-(3-morpholin-4-yl)propyl propionamide
  参考文献：
  名称：

  Synthesis and methods of use of purine analogues and derivatives

  摘要：

  一种嘌呤衍生物或类似物包括一个由9个原子构成的双环基团A，通过连接基L与基团B相连，其中B是一个羧酸，羧酸酯或结构为N（Y1）-D的基团，其中Y1可以是多种取代基之一，包括氢或烷基，D是增强衍生物或类似物的药理效应，促进吸收或血脑屏障穿透的基团。基团A有一个融合了一个五元环的六元环。基团A可以在五元环中有一个、两个或三个氮原子，并在六元环中有两个氮原子。基团A可以是一种嘌呤基团。基团B可以是多种基团之一，包括具有智力增强活性或其他生物或生理活性的基团。

  公开号：

  US20020156277A1

文献信息

• Methods for treatment of disease-induced peripheral neuropathy and related conditions
  申请人：Spectrum Pharmaceuticals, Inc.

  公开号：EP1790344A2

  公开（公告）日：2007-05-30

  The use of a compound of formula (I) in the manufacture of a medicament for the treatment of peripheral neuropathy. The compound can induce peripheral nerve sprouting through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting.

  将式（I）化合物用于制造治疗周围神经病变的药物。该化合物可通过神经生长因子（NGF）等神经营养因子的作用诱导周围神经萌发，而不会出现痛觉减退。外周神经萌发可以是痛觉神经萌发。
• Methods for stimulation of synthesis of synaptophysin in the central nervous system
  申请人：——

  公开号：US20020040032A1

  公开（公告）日：2002-04-04

  A method of increasing the synthesis and/or secretion of synaptophysin comprises administering to a patient with a neurological disease or a patient at risk of developing a neurological disease an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The neurological disease can be a neurodegenerative disease such as Alzheimer's disease or a neurodevelopmental disorder such as Down's syndrome. Typically, the compound can pass through the blood-brain barrier. The purine moiety can be hypoxanthine or guanine. A particularly preferred purine derivative is N-4-carboxyphenyl-3-(6-oxohydropurin-9-yl) propanamide.

  一种增加突触素合成和/或分泌的方法包括向神经系统疾病患者或有患神经系统疾病风险的患者施用有效量的嘌呤衍生物或类似物、四氢吲哚酮衍生物或类似物或嘧啶衍生物或类似物。如果化合物是嘌呤衍生物，嘌呤分子可以是鸟嘌呤或次黄嘌呤。神经系统疾病可以是神经退行性疾病，如阿尔茨海默病，也可以是神经发育障碍，如唐氏综合征。通常情况下，化合物可以通过血脑屏障。嘌呤分子可以是次黄嘌呤或鸟嘌呤。一种特别优选的嘌呤衍生物是 N-4-羧基苯基-3-（6-氧代氢嘌呤-9-基）丙酰胺。
• Methods for prevention of accumulation of amyloid beta peptide in the central nervous system
  申请人：——

  公开号：US20020040031A1

  公开（公告）日：2002-04-04

  A method of either inhibiting the formation of A&bgr; or stimulating the formation of sAPP comprises administering to a patient with a neurological disease or a patient at risk of developing a neurological disease an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The neurological disease can be a neurodegenerative disease such as Alzheimer's disease or a neurodevelopmental disorder such as Down's syndrome. Typically, the compound can pass through the blood-brain barrier. The purine moiety can be hypoxanthine or guanine. A particularly preferred purine derivative is N-4-carboxyphenyl-3-(6-oxohydropurin-9-yl) propanamide.

  一种抑制 A&bgr 形成或刺激 sAPP 形成的方法包括向神经系统疾病患者或有患神经系统疾病风险的患者施用有效量的嘌呤衍生物或类似物、四氢吲哚酮衍生物或类似物或嘧啶衍生物或类似物。如果化合物是嘌呤衍生物，嘌呤分子可以是鸟嘌呤或次黄嘌呤。神经系统疾病可以是神经退行性疾病，如阿尔茨海默病，也可以是神经发育障碍，如唐氏综合征。通常情况下，化合物可以通过血脑屏障。嘌呤分子可以是次黄嘌呤或鸟嘌呤。一种特别优选的嘌呤衍生物是 N-4-羧基苯基-3-（6-氧代氢嘌呤-9-基）丙酰胺。
• Methods for treatment of drug-induced peripheral neuropathy and related conditions
  申请人：——

  公开号：US20020061899A1

  公开（公告）日：2002-05-23

  A method of treating drug-induced peripheral neuropathy comprises administering to a patient with drug-induced peripheral neuropathy an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The compound can induce peripheral nerve sprouting through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting. The drug-induced peripheral neuropathy can be drug-induced peripheral neuropathy associated with the administration of oncolytic drugs, such as a vinca alkaloid, cisplatin, paclitaxel, suramin, altretamine, carboplatin, chlorambucil, cytarabine, dacarbazine, docetaxel, etoposide, fludarabine, ifosfamide with mesna, tamoxifen, teniposide, or thioguanine. Methods according to the present invention are particularly useful in treating peripheral neuropathy associated with the administration of vincristine, paclitaxel, or cisplatin.

  一种治疗药物性周围神经病变的方法包括向药物性周围神经病变患者施用有效量的嘌呤衍生物或类似物、四氢吲哚酮衍生物或类似物或嘧啶衍生物或类似物。如果化合物是嘌呤衍生物，嘌呤分子可以是鸟嘌呤或次黄嘌呤。该化合物可通过神经生长因子（NGF）等神经营养因子的作用诱导外周神经萌发，而不会出现痛觉减退。外周神经萌发可以是痛觉神经萌发。药物诱导的周围神经病变可以是与服用溶瘤药物相关的药物诱导的周围神经病变，如长春花生物碱、顺铂、紫杉醇、苏拉明、阿曲他胺、卡铂、氯霉素、阿糖胞苷、达卡巴嗪、多西他赛、依托泊苷、氟达拉滨、伊福法胺与美司那、他莫昔芬、替尼泊苷或硫鸟嘌呤。根据本发明的方法尤其适用于治疗与长春新碱、紫杉醇或顺铂用药相关的周围神经病变。
• Use of 9-substituted purine analogues and other molecules to stimulate neurogenesis
  申请人：Eve M. Taylor

  公开号：US20020091133A1

  公开（公告）日：2002-07-11

  The present invention is directed to a method of inducing neurogenesis by administering to a mammal an effective quantity of a compound that induces neurogenesis, where neurogenesis includes proliferation of neural stem and progenitor cells, differentiation of these cells into neurons, and/or survival of these new neurons. In general, the compound comprises three moieties, A, L, and B, covalently linked. A can be a purine, tetrahydroindolone, or pyrimidine; L is a linker, while B is a moiety that promotes absorption of the compound. A particularly preferred compound is N4-[[3-(6-oxo-1,6-dihydropurin-9-yl)-1-oxopropyl] amino] benzoic acid (also known as AIT-082 or leteprinim potassium). Another aspect of the invention is pharmaceutical compositions for inducing neurogenesis.

  本发明涉及一种诱导神经发生的方法，通过向哺乳动物施用有效量的诱导神经发生的化合物，其中神经发生包括神经干细胞和祖细胞的增殖、这些细胞分化成神经元和/或这些新神经元的存活。一般来说，化合物由共价连接的三个分子 A、L 和 B 组成。A 可以是嘌呤、四氢吲哚酮或嘧啶；L 是连接剂，而 B 是促进化合物吸收的分子。一种特别优选的化合物是 N4-[[3-(6-氧代-1,6-二氢嘌呤-9-基)-1-氧代丙基]氨基]苯甲酸（又称 AIT-082 或来替普林钾）。本发明的另一方面是用于诱导神经发生的药物组合物。