6-羟基-2-氮杂-双环[2.2.1]庚烷-2-羧酸叔丁酯 | 198835-02-8

• 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: 6-羟基-2-氮杂-双环[2.2.1]庚烷-2-羧酸叔丁酯
• 英文名称: (1S,4R,6S)-tert-butyl 6-hydroxy-2-azabicyclo[2,2,1]heptane-2-carboxylate
• 英文别名: tert-butyl (1S,4R,6S)-6-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylate；(1S,4R,6S)-2-Aza-2-(t-butoxycarbonyl)-bicyclo[2.2.1]heptan-6-ol
• CAS: 198835-02-8
• 化学式: C₁₁H₁₉NO₃
• 分子量: 213.277
• InChiKey: PABFVGKPNHVSCG-VGMNWLOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-羟基-2-氮杂-双环[2.2.1]庚烷-2-羧酸叔丁酯 在 盐酸 、 L-Selectride 、 sodium hydride 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 11.83h， 生成 (1S,4R,6R)-6-((5-(trifluoromethyl)pyridin-2-yl)oxy)-2-azabicyclo[2,2,1]heptane hydrochloride
  参考文献：
  名称：

  US2014/275118

  摘要：

  公开号：
• 作为产物：
  描述：

  (1S)-(+)-2-氮杂双环[2.2.1]庚-5-烯-3-酮 在 lithium aluminium tetrahydride 、 mercury(II) diacetate 、 水 、 N,N-二异丙基乙胺 作用下， 生成 6-羟基-2-氮杂-双环[2.2.1]庚烷-2-羧酸叔丁酯
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035

文献信息

• Heterocyclic compounds
  申请人：Eli Lilly and Company

  公开号：US06124312A1

  公开（公告）日：2000-09-26

  The present invention provides heterocyclic 2-aza-bicyclo[2.2.1]heptane compounds which are useful for modulating a muscarinic ptor.

  本发明提供了对调节肌胆碱受体有用的杂环2-aza-bicyclo[2.2.1]庚烷化合物。
• SUBSTITUTED 2-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS
  申请人：Janssen Pharmaceutica NV

  公开号：US20150174129A1

  公开（公告）日：2015-06-25

  The present invention is directed to compounds of Formula I: wherein X is N or CR 1 ; Y is N or CR 2 ; R 1 is H, alkoxy, halo, triazolyl, pyrimidinyl, oxazolyl, isoxazole, oxadiazolyl, or pyrazolyl; R 2 is H, alkyl, alkoxy, or halo; Z is NH or O; R 3 is H, alkyl, alkoxy, halo, or triazolyl; R 4 is H or alkyl; or R 3 and R 4 , together with the atoms to which they are attached, form a 6-membered aryl ring or a 5- or 6-membered heteroaryl ring; R 5 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，噻二唑基或吡唑基；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与它们所连接的原子一起形成一个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性地用卤素或烷基取代；n为1或2。本发明还描述了制备式I化合物的方法。本发明还涉及包含式I化合物的制药组合物。使用本发明中的化合物的方法也在本发明的范围内。
• 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。
• 10.1021/acs.jmedchem.4c00978
  作者：Hicken, Erik J.、Brown, Karin、Dwulet, Natalie C.、Gaudino, John J.、Hansen, Erik P.、Hartley, Dylan P.、Kowalski, John P.、Laird, Ellen R.、Lazzara, Nicholas C.、Li, Bin、Mou, Tung-Chung、Mutryn, Marie F.、Oko, Lauren、Pajk, Spencer、Pipal, Robert W.、Rosen, Rachel Z.、Shelp, Russell、Singh, Anurag、Wang, Jing、Wise, Courtney E.、Wong, Christina、Wong, Jim Y.

  DOI：10.1021/acs.jmedchem.4c00978

  日期：——

  The goal of this work was to identify a TKI that would provide robust inhibition of oncogenic HER2WT and HER2 mutants while sparing EGFRWT activity. Herein, we describe the development of a potent, covalent inhibitor of HER2WT and the YVMA insertion mutant while providing oral bioavailability and avoiding the inhibition of EGFRWT.

  HER2 过度表达和扩增已被确定为致癌驱动因素，并且治疗含有这些标记物的肿瘤的疗法的开发受到了相当大的关注。 HER2 突变也可以诱导 HER2 信号传导的激活和随后的细胞生长，包括激酶结构域内外显子 20 中常见的 YVMA 插入。 Enhertu 是目前唯一获批治疗 NSCLC HER2 突变肿瘤的药物。在该领域测试的 TKI 存在脱靶活性，主要是由于 EGFR WT抑制或针对 HER2 突变体的活性减弱。这项工作的目标是确定一种 TKI，它可以对致癌 HER2 WT和 HER2 突变体提供强力抑制，同时保留 EGFR WT活性。在此，我们描述了 HER2 WT和 YVMA 插入突变体的有效共价抑制剂的开发，同时提供口服生物利用度并避免 EGFR WT的抑制。
• PIPERAZINO DERIVATIVES AS NEUROKININ ANTAGONISTS
  申请人：SCHERING CORPORATION

  公开号：EP0937069B1

  公开（公告）日：2006-05-03