benzyl 6-oxo-2-azabicyclo[2.2.2]octane-2-carboxylate | 128507-95-9

• 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: benzyl 6-oxo-2-azabicyclo[2.2.2]octane-2-carboxylate
• 英文别名: 2-benzyloxycarbonyl-2-azabicyclo[2.2.2]octan-6-one；2-Azabicyclo[2.2.2]octane-2-carboxylic acid, 6-oxo-, phenylmethyl ester
• CAS: 128507-95-9
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: MTJSGAQOVNOGQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 6-oxo-2-azabicyclo[2.2.2]octane-2-carboxylate 、 2-碘-6-甲基吡嗪 生成 6-(6-Methylpyrazin-2-yl)-2-benzyloxycarbonyl-2-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Substituted pyrazines, pyrimidines and pyridazines for use in the

  摘要：

  一类吡嗪、嘧啶和吡啶衍生物，被非芳香性氮杂双环环系统取代，并且可选地被多达两个进一步的取代基所取代，适用于制备药物，特别是适用于局部给药于眼睛的制剂，适用于治疗青光眼和/或降低眼内压。

  公开号：

  US05219849A1

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 pyridines, their preparation, formulations and use in dementia
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0412798A2

  公开（公告）日：1991-02-13

  Pyridines, substituted by a non-aromatic azacyclic or non-fused azabicyclic ring system and a substituent of low lipophilicity or a hydrocarbon substituent, their salts and prodrugs, and formulations thereof are useful in the treatment of neurodegenerative disorders such as dementia. The compounds can be synthesised by methods analogous to these known in the art.

  由非芳香氮杂环或非融合氮杂环环系和低亲脂性取代基或烃类取代基取代的吡啶类化合物、其盐类和原药及其制剂可用于治疗神经退行性疾病，如痴呆症。这些化合物的合成方法类似于本领域已知的方法。
• Substituted pyrazines, pyrimidines and pyridazines for use in the treatment of glaucoma
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0492903A1

  公开（公告）日：1992-07-01

  The use of a compound of structural formula (I): or a pharmaceutically acceptable salt thereof or a prodrug thereof; wherein    one of X, Y and Z represents nitrogen and the remainder represent carbon atoms;    R¹ represents a non-aromatic, azabicyclic ring system selected from: wherein the broken line represents an optional chemical bond;    the substituents R³ and R⁴ may be present at any position, including the point of attachment to the pyrazine, pyridazine or pyrimidine ring, and independently represent hydrogen, C₁₋₄ alkyl, halogen, C₁₋₄ alkoxy, hydroxy, carboxy or C₁₋₄ alkoxycarbonyl; or R³ and R⁴ together represent carbonyl; and R⁵ represents hydrogen or C₁₋₄ alkyl; and    R² and R¹¹ independently represent hydrogen, halogen, -CF₃, -OR⁶, -NR⁶R⁷, -CN, C₁₋₈ alkyl or C₂₋₈ alkenyl; wherein R⁶ is hydrogen or C₁₋₆ alkyl; and R⁷ is hydrogen or C₁₋₆ alkyl; for the manufacture of a medicament for treating glaucoma and/or for reducing intraocular pressure.

  使用结构式(I)的化合物： 或其药学上可接受的盐或其原药； 其中 X、Y 和 Z 中的一个代表氮，其余代表碳原子； R¹代表选自下列的非芳香族氮杂环环系统 其中断线代表任选的化学键； 取代基 R³ 和 R⁴ 可存在于任何位置，包括吡嗪、哒嗪或嘧啶环的连接点，并独立地代表氢、C₁₋₄烷基、卤素、C₁₋₄烷氧基、羟基、羧基或 C₁₋₄烷氧羰基；或 R³ 和 R⁴ 共同代表羰基；且 R⁵ 代表氢或 C₁₋₄ 烷基；且 R²和R¹¹独立地代表氢、卤素、-CF₃、-OR⁶、-NR⁶R⁷、-CN、C₁₋₈烷基或C₂₋₈烯基；其中R⁶是氢或C₁₋₆烷基；R⁷是氢或C₁₋₆烷基； 用于制造治疗青光眼和/或降低眼压的药物。
• 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