(1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptane | 309962-76-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptane
• 英文别名: rac-(1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptane；(2R,5R)-6-benzyl-2,6-diaza-bicyclo[3.2.0]heptane；(1R,5R)-6-benzyl-2,6-diazabicyclo[3.2.0]heptane
• CAS: 309962-76-3
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: YCEMQEOVBUUXAV-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 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：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptane 、 2-(5-amino-4,6-dimethyl-pyrimidin-2-yl)oxyacetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以48%的产率得到2-(5-amino-4,6-dimethyl-pyrimidin-2-yl)oxy-1-[(1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptan-4-yl]ethanone
  参考文献：
  名称：

  Fibroblast growth factor receptor modulators employing diamines with reduced phospholipidosis-inducing potential

  摘要：

  SUN13837 (1), a fibroblast growth factor receptor modulator, has been an attractive candidate for treating neurodegenerative diseases. However, one of its metabolites, N-benzyl-4-(methylamino)piperidine (BMP), turned out to possess phospholipidosis-inducing potential (PLIP) in vitro. To obtain SUN13837 analogs with reduced phospholipidosis risk, we replaced BMP with other diamines possessing low PLIP. Our effort led to the discovery of compound 6 with increased efficacy. Further structural modifications to reduce hydrogen bond donors afforded 17 with improved brain exposure. Oral administration of 17 at 1 mg/kg once daily for 10 days showed enhanced recovery of coordinated movement in a rat acute stroke model, suggesting that it is a promising follow-up compound for 1 with reduced risk of phospholipidosis.

  DOI：

  10.1016/j.bmc.2020.115562
• 作为产物：
  描述：

  反-3-羟基-L-脯氨酸 在 硼烷四氢呋喃络合物 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 64.0h， 生成 (1R,5R)-7-benzyl-4,7-diazabicyclo[3.2.0]heptane
  参考文献：
  名称：

  Second basic pKa: An overlooked parameter in predicting phospholipidosis-inducing potential of diamines

  摘要：

  In this paper, we present the phospholipidosis-inducing potential (PLIP) of forty fragment-sized diamines derived from N-benzyl-4-(methylamino)piperidine and discuss the relationship between their PLIP and the physicochemical properties. Our results demonstrate that the previously reported methods are not suitable for predicting the PLIP of fragment-sized diamines; the second basic pKa can distinguish PLIP-positive diamines from PLIP-negative diamines more accurately than ClogP or most basic pKa. To the best of our knowledge, this is the first report describing the relationship between PLIP and second basic pKa.

  DOI：

  10.1016/j.bmcl.2019.126933

文献信息

• Substituted diazabicycloalkane derivatives
  申请人：Basha Anwer

  公开号：US20050101602A1

  公开（公告）日：2005-05-12

  Compounds of formula (I) Z-Ar 1 —Ar 2 (I) wherein Z is a diazabicyclic amine, Ar 1 is a 5- or 6-membered aromatic ring, and Ar 2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.

  式(I)的化合物 Z-Ar 1 —Ar 2 (I) 其中Z是一种二氮杂双环胺，Ar 1 是一个5-或6-成员芳香环，Ar 2 选自未取代或取代的5-或6-成员杂芳基环；未取代或取代的双环杂芳基环；3,4-(亚甲二氧基)苯基；咔唑基；四氢咔唑基；萘基；和苯基；其中苯基在间位或对位上取代有0、1、2或3个取代基。这些化合物在治疗由α7 nAChR配体预防或改善的病症或紊乱中有用。还公开了包含式(I)的化合物的药物组合物以及使用这些化合物和组合物的方法。
• Diazabicyclic central nervous system active agents
  申请人：——

  公开号：US20020019388A1

  公开（公告）日：2002-02-14

  Compounds of formula I 1 pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  式I1的化合物，这些化合物的药物组合物，以及利用这些组合物来控制哺乳动物的突触传递。
• Heterocyclic substituted aminoazacycles useful as central nervous system agents
  申请人：ABBOTT LABORATORIES

  公开号：EP1428824A1

  公开（公告）日：2004-06-16

  Heterocyclic substituted aminoazacyclic compounds of the formula (I):Z-R3, wherein Z is a defined aminoazacycle and R3 is a defined heterocycle moiety, pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  异环取代氨基环化合物的化学式(I)：Z-R3，其中Z是定义的氨基环，R3是定义的杂环基团，这些化合物的药物组合物，以及利用所述组合物来控制哺乳动物的突触传递。
• DIAZABICYCLIC CENTRAL NERVOUS SYSTEM ACTIVE AGENTS
  申请人：Schrimpf R. Michael

  公开号：US20080097094A1

  公开（公告）日：2008-04-24

  Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  化合物I的配方药物组合物，以及使用该组合物来控制哺乳动物的突触传递。
• Heterocyclic Substituted Aminoazacycles Useful as Central Nervous System Agents
  申请人：Schrimpf R. Michael

  公开号：US20080090798A1

  公开（公告）日：2008-04-17

  Heterocyclic substituted aminoazacyclic compounds of formula I Z-R 3 I, wherein Z is a defined aminoazacycle and R 3 is a defined heterocycle moiety, pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  公式I Z-R3I中的杂环取代氨基杂环化合物，其中Z是定义的氨基杂环，R3是定义的杂环基团，这些化合物的制药组成物及其在哺乳动物中控制突触传递的用途。