(1S,5R)-3,6-二氮杂双环[3.2.0]庚烷-6-羧酸叔丁酯 | 370882-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 中文名称: (1S,5R)-3,6-二氮杂双环[3.2.0]庚烷-6-羧酸叔丁酯
• 英文名称: (1S,5R)-tert-butyl 3,6-diazabicyclo[3.2.0]heptane-6-carboxylate
• 英文别名: tert-butyl (1S,5R)-3,6-diaza-bicyclo[3.2.0]heptane-3-carboxylate；tert-butyl-(1S,5R)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate；tert-butyl-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate；tert-butyl (1S,5R)-3,6-diazabicyclo[3.2.0]heptan-6-carboxylate；(1S,5R)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid 1,1-dimethylethyl ester；(1S,5R)-3,6-diaza-bicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester；Tert-butyl (1s,5r)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate
• CAS: 370882-66-9
• 化学式: C₁₀H₁₈N₂O₂
• 分子量: 198.265
• InChiKey: YPCQQZHIBTVQAB-YUMQZZPRSA-N

物化性质

• 沸点：
  276.4±13.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：2-8°C，密封保存，避免潮湿。

反应信息

• 作为反应物：
  描述：

  (1S,5R)-3,6-二氮杂双环[3.2.0]庚烷-6-羧酸叔丁酯 在 tris(dibenzylideneacetone)dipalladium (0) caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 、 三氟乙酸 为溶剂， 反应 41.0h， 生成 5-[(1R,5R)-3,6-diazabicyclo[3.2.0]heptan-3-yl]nicotinonitrile
  参考文献：
  名称：

  A-366833: A novel nicotinonitrile-substituted 3,6-diazabicyclo[3.2.0]-heptane α4β2 nicotinic acetylcholine receptor selective agonist: Synthesis, analgesic efficacy and tolerability profile in animal models

  摘要：

  5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) is a novel nicotinic acetylcholine receptor (nAChR) ligand that binds to the agonist-binding site ([H-3]-cytisine) with K-i value of 3.1 nM and exhibits agonist selectivity at alpha 4 beta 2 nAChR relative to the alpha 3 beta 4 nAChR subtype. The analgesic effects of A-366833 were examined across a variety of animal models including the mouse model of writhing pain (abdominal constriction), the rat models of acute thermal (hot box), persistent chemical (formalin) and neuropathic (spinal nerve ligation, SNL) pain. In the abdominal constriction model, A-366833 was effective at doses ranging from 0.062 to 0.62 mu mol/kg (i.p.). In addition, A-366833 demonstrated significant effects in acute thermal pain (6.2-19.0 mu mol/kg, i.p.), formalin (1.9-19 mu mol/kg i.p.) and SNL (1.9-19 mu mol/kg i.p.) models. The systemic effects of A-366833 were attenuated by pretreatment with mecamylamine (5 mu mol/kg i.p.) in both the formalin and SNL models, suggesting that the analgesic effects of A-366833 in models of persistent nociceptive and neuropathic pain are mediated by activation of nAChRs. Pharmacokinetic investigations of A-366833 in rat revealed moderate brain:plasma distribution, half-life of 1.5 h and excellent oral bioavailability of 73%. Comparison of peak plasma levels at the minimal effective doses across rat models of acute thermal pain, formalin and SNL with the maximal exposure that does not evoke emesis in ferret revealed therapeutic margins ranging from 6- to 22-fold. These studies indicate that compounds like A-366833 with improved agonist selectivity at alpha 4 beta 2 vs. alpha 3 beta 4 nAChR can elicit a broad spectrum of analgesic efficacy without concurrent adverse effects. (C) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.08.010
• 作为产物：
  描述：

  (1S,5R)-3-benzyl 6-tert-butyl 3,6-diazabicyclo[3.2.0]heptane-3,6-dicarboxylate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以97%的产率得到(1S,5R)-3,6-二氮杂双环[3.2.0]庚烷-6-羧酸叔丁酯
  参考文献：
  名称：

  3,6-二氮杂双环[3.2.0]庚烷作为新型α4β2烟碱型乙酰胆碱受体选择性激动剂的合成及构效关系研究。

  摘要：

  合成了一系列从3,6-二氮杂双环[3.2.0]庚烷衍生的新型有效神经元烟碱乙酰胆碱受体（nAChR）配体，并评估了其对alpha4beta2 nAChR亚型的结合亲和力和激动剂活性。这些新型nAChR配体的结构活性关系研究集中于对吡啶环的取代作用以及3,6-二氮杂双环[3.2.0]庚烷核心的立体和区域化学影响。吡啶环上的5个小取代基对结合亲和力和功能活性影响不大。吡啶环上的6-溴，6-氯和6-甲基取代基导致增加的结合亲和力和改善的功能活性。大多数6-N-吡啶基取代的3,6-二氮杂双环[3.2.0]庚烷对alpha4beta2 nAChR亚型具有选择性。化合物（1R，5S）-25，（1R，5S）-55，和（1R，5S）-56在halpha3beta4 nAChR上几乎没有活性，但在halpha4beta2 nAChR亚型上保留了效力和功效。3-N-吡啶基取代的系列显示出更复杂的SAR。发现（

  DOI：

  10.1021/jm070755h

文献信息

• Substituted diazabicycloakane derivatives
  申请人：Basha Anwer

  公开号：US20050065178A1

  公开（公告）日：2005-03-24

  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 an unsubstituted or substituted 5-membered heteroaryl ring; an unsubstituted or substituted 6-membered heteroaryl ring; 3,4-(methylenedioxy)phenyl; and phenyl 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 从未取代或取代的5-成员杂芳基环；一个未取代或取代的6-成员杂芳基环；3,4-(亚甲二氧基)苯基；和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方面是有用的。还公开了包括式(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。
• [EN] PYRAZOLOTRIAZINES<br/>[FR] PYRAZOLOTRIAZINES
  申请人：BAYER AG

  公开号：WO2021116178A1

  公开（公告）日：2021-06-17

  The present invention provides compounds of general formula (I), in which X, R1, R2 and R3 are as described and defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of hyperproliferative disorders such as cancer disorders, as a sole agent or in combination with other active ingredients.

  本发明提供了具有通用公式（I）的化合物，其中X，R1，R2和R3如本文所述和定义，制备所述化合物的方法，用于制备所述化合物的有用中间化合物，包含所述化合物的药物组合物和组合，以及使用所述化合物用于制造用于治疗和/或预防疾病的药物组合物，特别是作为单一剂或与其他活性成分结合使用的过度增殖障碍，如癌症疾病。
• ISOQUINOLINESULFONYL DERIVATIVE AS RHO KINASE INHIBITOR
  申请人：MEDSHINE DISCOVERY INC.

  公开号：US20170037050A1

  公开（公告）日：2017-02-09

  The present invention discloses a class of isoquinolinesulfonyl derivatives as RHO kinase inhibitors, and pharmaceutical compositions thereof, and relates to pharmaceutically acceptable uses thereof. Specifically, the present invention relates to a compound as represented by formula (I), or a pharmaceutically acceptable salt thereof.

  本发明公开了一类异喹啉磺酰衍生物作为RHO激酶抑制剂，以及其药物组合物，并涉及它们的药用可接受用途。具体而言，本发明涉及如式(I)所示的化合物，或其药用可接受的盐。
• [EN] ERBB/BTK INHIBITORS<br/>[FR] INHIBITEURS DE ERBB/BTK
  申请人：DIZAL JIANGSU PHARMACEUTICAL CO LTD

  公开号：WO2019149164A1

  公开（公告）日：2019-08-08

  Disclosed are compounds inhibiting ErbBs (e. g., EGFR or Her 2), especially mutant forms of ErbBs, and BTK, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat ErbBs (especially mutant forms of ErbBs) or BTK associated diseases, including cancer.

  揭示了抑制ErbBs（例如EGFR或Her 2），特别是ErbBs的突变形式，以及BTK的化合物，其药用盐、水合物、溶剂合物或立体异构体，以及包含这些化合物的药物组合物。该化合物和药物组合物可以有效治疗ErbBs（特别是ErbBs的突变形式）或与BTK相关的疾病，包括癌症。
• 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。