2-苄基-6-羟基-2-氮杂双环[2.2.2]辛烷 | 41959-29-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 2-苄基-6-羟基-2-氮杂双环[2.2.2]辛烷
• 英文名称: 2-benzyl-6-trans-hydroxy-2-azabicyclo[2.2.2]octane
• 英文别名: 2-benzyl-6-endo-hydroxy-2-azabicyclo[2.2.2]octane；endo-2-benzyl-2-azabicyclo[2.2.2]octan-6-ol；2-benzyl-2-azabicyclo[2.2.2]octan-6-exo-ol；2-benzyl-2-aza-bicyclo[2.2.2]octan-6-ol；2-Benzyl-6-trans-hydroxy-2-azabicyclo<2.2.2>octan；2-Benzyl-6-hydroxy-2-azabicyclo[2.2.2]octane；2-benzyl-2-azabicyclo[2.2.2]octan-6-ol
• CAS: 41959-29-9
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: LSQZRPLAUOVRPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  332.4±25.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 储存条件：
  存储条件：2-8°C，密封于干燥处。

反应信息

• 作为反应物：
  描述：

  2-苄基-6-羟基-2-氮杂双环[2.2.2]辛烷 以86%的产率得到2-benzyl-6-exo-diphenylmethoxy-2-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Certain 1-azabicyclo[2.2.1]heptanes useful as muscarinic receptor

  摘要：

  以下是中文翻译：MUSCARINIC受体拮抗剂的以下化学式：##STR1## Muscarinic受体拮抗剂，特别适用于治疗肠易激综合征，其化学式为(IA)或(IB)或其药用盐，其中R.sup.2和R.sup.3各自独立地为H、卤素或C.sub.1 -C.sub.4烷基；m为0、1或2；n为1、2或3；Y为直链、O或S；但当n为1时，Y为直链；Het为化学式(A)或(B)的基团，其中p为0、1或2，q为1、2或3，r为0、1、2或3，但要求p、q和r的总和至少为3，"Het"的N原子连接到化学式(IA)中(CH.sub.2).sub.n的基团和化学式(IB)中的H原子；R.sup.1为化学式(a)、(b)或Het.sup.1的基团，其中R.sup.4和R.sup.5各自独立地为H、C.sub.1 -C.sub.4烷基、C.sub.1 -C.sub.4烷氧基、--(CH.sub.2).sub.t OH、卤素、三氟甲基、氰基、--(CH.sub.2).sub.t NR.sup.6 R.sup.7、--CO(C.sub.1 -C.sub.4烷基)、--OCO(C.sub.1 -C.sub.4烷基)、CH(OH)(C.sub.1 -C.sub.4烷基)、--C(OH)(C.sub.1 -C.sub.4烷基).sub.2、--SO.sub.2 NH.sub.2、--(CH.sub.2).sub.t CONR.sup.6 R.sup.7或--(CH.sub.2).sub.t COO(C.sub.1 -C.sub.4烷基)；R.sup.6和R.sup.7各自独立地为H或C.sub.1 -C.sub.4烷基；t为0、1或2；X和X.sup.1各自独立地为O或CH.sub.2；s为1、2或3；Het.sup.1为吡啶基、吡嗪基或噻吩基。

  公开号：

  US05397800A1
• 作为产物：
  描述：

  2-Benzyl-6-hydroxy-2-aza-bicyclo<2.2.2>octan-3-on 在 sodium hydroxide 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 生成 2-苄基-6-羟基-2-氮杂双环[2.2.2]辛烷
  参考文献：
  名称：

  5-(1,1-Diphenyl-3-(5- or

  摘要：

  这项发明涵盖了新颖的5-[1,1-二苯基-3-(5-或6-羟基-2-氮杂双环[2.2.2]辛-2-基)丙基]-2-烷基-1,3,4-噁二唑及其较低的O-烷酰衍生物。这些化合物是有用的抗腹泻药物，同时几乎没有镇痛活性。

  公开号：

  US04013668A1

文献信息

• BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
  申请人：Lampe John W.

  公开号：US20110144150A1

  公开（公告）日：2011-06-16

  The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. The method comprises administering to a subject a therapeutically effective amount of a Rho kinase inhibitory compound of Formula I, wherein said amount is effective to influence the actomyosin interactions, for example, by leading to cellular relaxation and alterations in cell-substratum adhesions. In one embodiment, the method treats increased intraocular pressure, such as primary open-angle glaucoma. In another embodiment, the method treats diseases or conditions of the lung associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema.

  本发明涉及一种合成的桥接双环化合物，该化合物是rho相关蛋白激酶的抑制剂。本发明还涉及包括这些化合物和药用可接受载体的药物组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或症状的方法。该方法包括向受试者施用一定量的具有治疗作用的公式I的Rho激酶抑制剂化合物，其中该量有效地影响肌动蛋白互作，例如，通过导致细胞松弛和细胞-基质粘附的改变。在一种实施方式中，该方法治疗增加的眼内压，如原发性开角青光眼。在另一种实施方式中，该方法治疗与肺部细胞过度增殖、重塑、炎症、血管收缩、支气管收缩、气道高反应性和水肿相关的疾病或症状。
• BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITIONS AND USE
  申请人：Lampe John W.

  公开号：US20130281485A1

  公开（公告）日：2013-10-24

  The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. The method comprises administering to a subject a therapeutically effective amount of a Rho kinase inhibitory compound of Formula I, wherein said amount is effective to influence the actomyosin interactions, for example, by leading to cellular relaxation and alterations in cell-substratum adhesions. In one embodiment, the method treats increased intraocular pressure, such as primary open-angle glaucoma. In another embodiment, the method treats diseases or conditions of the lung associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema.

  本发明涉及一种合成的桥接双环化合物，它们是rho相关蛋白激酶的抑制剂。本发明还涉及包含这种化合物和药用载体的制药组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或病症的方法。该方法包括向受试者施用一种公式I的Rho激酶抑制化合物的治疗有效量，其中该量对影响肌动蛋白相互作用有效，例如通过导致细胞松弛和细胞-基质附着的变化。在一种实施方式中，该方法治疗增加的眼压，例如原发性开角型青光眼。在另一种实施方式中，该方法治疗与过度细胞增殖、重塑、炎症、血管收缩、支气管收缩、气道高反应性和水肿相关的肺部疾病或病症。
• SUBSTITUTED 2-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20160052939A1

  公开（公告）日：2016-02-25

  The present invention is directed to compounds of Formula I: wherein X is N or CR1; Y is N or CR2; R1 is H, alkoxy, halo, triazolyl, pyrimidinyl, oxazolyl, isoxazole, oxadiazolyl, or pyrazolyl; R2 is H, alkyl, alkoxy, or halo; Z is NH or O; R3 is H, alkyl, alkoxy, halo, or triazolyl; R4 is H or alkyl; or R3 and R4, together with the atoms to which they are attached, form a 6-membered aryl ring or a 5- or 6-membered heteroaryl ring; R5 is pyridyl, pyrazinyl, or pyrimidinyl, wherein the pyridyl, pyrazinyl, or pyrimidinyl is optionally substituted with halo or alkyl; and n is 1 or 2. Methods of making the compounds of Formula I are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I. Methods of using the compounds of the invention are also within the scope of the invention.

  本发明涉及式I的化合物：其中X为N或CR1; Y为N或CR2; R1为H、烷氧基、卤素、三唑基、嘧啶基、噁唑基、异噁唑基、氧化二唑基或吡唑基; R2为H、烷基、烷氧基或卤素; Z为NH或O; R3为H、烷基、烷氧基、卤素或三唑基; R4为H或烷基; 或R3和R4连同它们所连接的原子形成一个6元芳基环或5-或6元杂芳基环; R5为吡啶基、吡嗪基或嘧啶基，其中吡啶基、吡嗪基或嘧啶基可以选择地用卤素或烷基取代; n为1或2。还描述了制备式I化合物的方法。本发明还涉及包括式I化合物的制药组合物。使用本发明的化合物的方法也属于本发明的范围。
• Substituted 2-azabicycles and their use as orexin receptor modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US10183953B2

  公开（公告）日：2019-01-22

  The present invention is directed to compounds of Formula I: wherein X is N or CR1; Y is N or CR2; R1 is H, alkoxy, halo, triazolyl, pyrimidinyl, oxazolyl, isoxazole, oxadiazolyl, or pyrazolyl; R2 is H, alkyl, alkoxy, or halo; Z is NH or O; R3 is H, alkyl, alkoxy, halo, or triazolyl; R4 is H or alkyl; or R3 and R4, together with the atoms to which they are attached, form a 6-membered aryl ring or a 5- or 6-membered heteroaryl ring; R5 is pyridyl, pyrazinyl, or pyrimidinyl, wherein the pyridyl, pyrazinyl, or pyrimidinyl is optionally substituted with halo or alkyl; and n is 1 or 2. Methods of making the compounds of Formula I are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I. Methods of using the compounds of the invention are also within the scope of the invention.

  本发明涉及式 I 的化合物： 其中 X 是 N 或 CR1；Y 是 N 或 CR2；R1 是 H、烷氧基、卤代、三唑基、嘧啶基、噁唑基、异噁唑基、噁二唑基或吡唑基；R2 是 H、烷基、烷氧基或卤代；Z 是 NH 或 O；R3 是 H、烷基、烷氧基、卤代或三唑基；R4 是 H 或烷基；或 R3 和 R4 与它们所连接的原子一起形成 6 元芳基环或 5 元或 6 元杂芳基环； R5 是吡啶基、吡嗪基或嘧啶基，其中吡啶基、吡嗪基或嘧啶基任选被卤素或烷基取代；以及 n 是 1 或 2。本发明还描述了制造式 I 化合物的方法。本发明还涉及包含式 I 化合物的药物组合物。本发明化合物的使用方法也属于本发明的范围。
• Amino-substituted bridged azabicyclic quinolone carboxylic acids and esters
  申请人：PFIZER INC.

  公开号：EP0356193B1

  公开（公告）日：1994-02-16