5-azabicyclo[2.2.2]octan-3-one | 1521490-56-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-azabicyclo[2.2.2]octan-3-one
• 英文别名: 2-Azabicyclo[2.2.2]octan-6-one
• CAS: 1521490-56-1
• 化学式: C₇H₁₁NO
• 分子量: 125.17
• InChiKey: XXHNCKJWALKGCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-溴巴豆酸 、 N4-(3-chloro-4-fluorophenyl)thieno[2,3-d]pyrimidine-4,6-diamine 、 5-azabicyclo[2.2.2]octan-3-one 在 氯化亚砜 、 吡啶 、 sodium iodide 作用下， 以 二氯甲烷 、 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到(E)-N-(4-((3-chloro-4-fluorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(6-oxo-2-azabicyclo[2.2.2]octan-2-yl)but-2-enamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors

  摘要：

  A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 mu M, and those of 12 compounds were less than 0.010 mu M. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 mu M. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 mu M. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 mu M), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method. (c) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.01.035

文献信息

• SUBSTITUTED 2-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP3622956A1

  公开（公告）日：2020-03-18

  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。
• Substituted 2-Azabicycles And Their Use As Orexin Receptor Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20170204096A1

  公开（公告）日：2017-07-20

  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.
• US9611277B2
  申请人：——

  公开号：US9611277B2

  公开（公告）日：2017-04-04
• [EN] SUBSTITUTED 2-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS<br/>[FR] 2-AZABICYLES SUBSTITUÉS ET LEUR UTILISATION EN TANT QUE MODULATEURS DES RÉCEPTEURS D'OREXINE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014165070A1

  公开（公告）日：2014-10-09

  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.