3-[[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]methyl]-1-(4-fluorophenyl)indazole-4-carboxylic acid | 1198215-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]methyl]-1-(4-fluorophenyl)indazole-4-carboxylic acid
• CAS: 1198215-42-7
• 化学式: C₂₂H₂₃FN₄O₂
• 分子量: 394.449
• InChiKey: YZNCAODNXASSAK-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]methyl]-1-(4-fluorophenyl)indazole-4-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-(4-fluorophenyl)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one
  参考文献：
  名称：

  Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome

  摘要：

  Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.11.080
• 作为产物：
  描述：

  (S)-methyl 1-(4-fluorophenyl)-3-[(quinuclidin-3-ylamino)methyl]-1H-indazole-4-carboxylate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 3-[[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]methyl]-1-(4-fluorophenyl)indazole-4-carboxylic acid
  参考文献：
  名称：

  Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome

  摘要：

  Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.11.080

文献信息

• 5-HT3 RECEPTOR MODULATORS, METHODS OF MAKING, AND USE THEREOF
  申请人：Manning David D.

  公开号：US20090298809A1

  公开（公告）日：2009-12-03

  Novel 5-HT 3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.

  揭示了新型5-HT3受体调节剂。这些化合物用于治疗各种疾病，包括化疗诱发的恶心和呕吐、术后恶心和呕吐以及肠易激综合征。本发明还描述了制备这些化合物的方法。
• US8501729B2
  申请人：——

  公开号：US8501729B2

  公开（公告）日：2013-08-06
• US8710047B2
  申请人：——

  公开号：US8710047B2

  公开（公告）日：2014-04-29
• [EN] 5-HT3 RECEPTOR MODULATORS, METHODS OF MAKING, AND USE THEREOF<br/>[FR] MODULATEURS DU RÉCEPTEUR 5-HT3, PROCÉDÉS DE PRÉPARATION ET UTILISATION DE CEUX-CI
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2009155054A2

  公开（公告）日：2009-12-23

  Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.