2-adamantyl (3R)-3-aminopyrrolidine-1-carboxylate | 1192769-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-adamantyl (3R)-3-aminopyrrolidine-1-carboxylate
• CAS: 1192769-23-5
• 化学式: C₁₅H₂₄N₂O₂
• 分子量: 264.368
• InChiKey: USRLHSDIORKYDU-RVARXAPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-adamantyl (3R)-3-aminopyrrolidine-1-carboxylate 、 氯甲酸丙酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-(2-adamantyl) 3-(propoxycarbonylamino)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1

  摘要：

  Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC50 of 15.2 nM against human 11 beta-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l, both of which were >25% orally bioavailable in rat. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.142
• 作为产物：
  描述：

  (3R)-(2-adamantyl) 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-adamantyl (3R)-3-aminopyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1

  摘要：

  Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC50 of 15.2 nM against human 11 beta-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l, both of which were >25% orally bioavailable in rat. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.142

文献信息

• CARBAMATE AND UREA INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1
  申请人：Claremon David A.

  公开号：US20130244994A1

  公开（公告）日：2013-09-19

  This invention relates to novel compounds of the Formula (I) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds of the Formula (I) and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

  本发明涉及公式(I)的新化合物及其药学上可接受的盐和药物组合物，用于治疗与哺乳动物中11β-HSD1的调节或抑制有关的疾病。本发明还涉及公式(I)的新化合物的药物组合物以及它们在细胞中减少或控制皮质醇的产生或抑制皮质酮转化为皮质醇的方法的使用。
• US8828985B2
  申请人：——

  公开号：US8828985B2

  公开（公告）日：2014-09-09
• [EN] CARBAMATE AND UREA INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1<br/>[FR] INHIBITEURS DE LA 11-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE 1 À BASE DE CARBAMATE ET D'URÉE
  申请人：VITAE PHARMACEUTICALS INC

  公开号：WO2009131669A2

  公开（公告）日：2009-10-29

  This invention relates to novel compounds of the Formula I, II, III, IHa, NIb, IV, IVa, IVb, IVc, IVd, IVe, V, Va, Vb1 Vl, Vla, VIb, VII, Vila, VIIb, VIII, Vllla, VIIIb, IX, IXa, X, and Xa, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.
• Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1
  作者：Colin M. Tice、Wei Zhao、Paula M. Krosky、Barbara A. Kruk、Jennifer Berbaum、Judith A. Johnson、Yuri Bukhtiyarov、Reshma Panemangalore、Boyd B. Scott、Yi Zhao、Joseph G. Bruno、Lamont Howard、Jennifer Togias、Yuan-Jie Ye、Suresh B. Singh、Brian M. McKeever、Peter R. Lindblom、Joan Guo、Rong Guo、Herbert Nar、Annette Schuler-Metz、Richard E. Gregg、Katerina Leftheris、Richard K. Harrison、Gerard M. McGeehan、Linghang Zhuang、David A. Claremon

  DOI：10.1016/j.bmcl.2010.08.142

  日期：2010.11

  Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC50 of 15.2 nM against human 11 beta-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l, both of which were >25% orally bioavailable in rat. (C) 2010 Elsevier Ltd. All rights reserved.