t-butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate | 1251001-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: t-butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate
• 英文别名: tert-Butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate；tert-butyl spiro[1,2-dihydroindole-3,3'-pyrrolidine]-1'-carboxylate
• CAS: 1251001-95-2
• 化学式: C₁₆H₂₂N₂O₂
• 分子量: 274.363
• InChiKey: JKQANUVMMUBHNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  t-butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate 在 甲醇 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 乙酰氯 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Novel and selective spiroindoline-based inhibitors of sky kinase

  摘要：

  We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.036
• 作为产物：
  描述：

  2-氧代-1,2-二氢螺[吲哚-3,3-吡咯烷]-1-羧酸叔丁酯 在 sodium tetrahydroborate 、 碘 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到t-butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate
  参考文献：
  名称：

  Novel and selective spiroindoline-based inhibitors of sky kinase

  摘要：

  We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.036

文献信息

• NOVEL SPIROINDOLINE COMPOUND, AND MEDICINAL AGENT COMPRISING SAME
  申请人：KOWA COMPANY, LTD.

  公开号：US20140309207A1

  公开（公告）日：2014-10-16

  The present invention provides a novel compound represented by a general formula (1) as shown below, which has a glucokinase-activating action in the liver and pancreatic β-cells and which is useful as an agent for preventing and/or treating diseases caused by hyperglycemia, such as diabetes. A spiroindoline compound represented by the general formula (1), or a salt thereof, or a solvate of the compound or the salt: [wherein ring A represents a nitrogen-containing 5-10 membered heteroaryl group; R 1 and R 2 , which are the same or different, each represent a hydrogen atom, a halogen atom, a halo C 1-6 alkyl group, a C 6-10 aryl group, a cyano group, a C 1-6 alkyl group optionally having a substituent, a C 2-6 alkenyl group optionally having a substituent, etc.; R 3 represents a hydrogen atom, a C 1-6 alkyl group optionally having a substituent, etc.; and R 4 represents a hydrogen atom, a halogen atom, a C 1-6 alkyl group optionally having a substituent, etc.]

  本发明提供了一种新型化合物，其通式（1）如下所示，具有在肝脏和胰岛β细胞中激活葡萄糖激酶的作用，并可用作预防和/或治疗由高血糖引起的疾病，如糖尿病的药物。该通式（1）表示的螺环吲哚化合物，或其盐，或化合物或盐的溶剂：[其中环A代表含氮的5-10成员杂环基；R1和R2，相同或不同，分别代表氢原子，卤原子，卤代C1-6烷基，C6-10芳基，氰基，C1-6烷基，可选取代基，C2-6烯基，可选取代基等；R3代表氢原子，C1-6烷基，可选取代基等；R4代表氢原子，卤原子，C1-6烷基，可选取代基等。]
• Spiroindoline compound, and medicinal agent comprising same
  申请人：Kowa Company, Ltd.

  公开号：US08921576B2

  公开（公告）日：2014-12-30

  The present invention provides a novel compound represented by a general formula (1) as shown below, which has a glucokinase-activating action in the liver and pancreatic β-cells and which is useful as an agent for preventing and/or treating diseases caused by hyperglycemia, such as diabetes. A spiroindoline compound represented by the general formula (1), or a salt thereof, or a solvate of the compound or the salt: [wherein ring A represents a nitrogen-containing 5-10 membered heteroaryl group; R1 and R2, which are the same or different, each represent a hydrogen atom, a halogen atom, a halo C1-6 alkyl group, a C6-10 aryl group, a cyano group, a C1-6 alkyl group optionally having a substituent, a C2-6 alkenyl group optionally having a substituent, etc.; R3 represents a hydrogen atom, a C1-6 alkyl group optionally having a substituent, etc.; and R4 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group optionally having a substituent, etc.]

  本发明提供了一种新型化合物，其通式（1）如下所示，具有在肝脏和胰岛β细胞中激活葡萄糖激酶的作用，并且可用作预防和/或治疗由高血糖引起的疾病，如糖尿病的药物。通式（1）表示的螺内酰胺化合物，或其盐，或化合物或盐的溶剂:[其中，环A表示含氮的5-10成员杂环基；R1和R2，它们相同或不同，每个表示氢原子，卤原子，卤代C1-6烷基，C6-10芳基，氰基，可选有取代基的C1-6烷基，可选有取代基的C2-6烯基等；R3表示氢原子，可选有取代基的C1-6烷基等；R4表示氢原子，卤原子，可选有取代基的C1-6烷基等。]
• EP2781521
  申请人：——

  公开号：——

  公开（公告）日：——
• US8921576B2
  申请人：——

  公开号：US8921576B2

  公开（公告）日：2014-12-30
• Novel and selective spiroindoline-based inhibitors of sky kinase
  作者：Noel A. Powell、Jeffrey T. Kohrt、Kevin J. Filipski、Michael Kaufman、Derek Sheehan、Jeremy E. Edmunds、Amy Delaney、Yuli Wang、Francis Bourbonais、Doh-Yeel Lee、Frank Schwende、Fang Sun、Pat McConnell、Cornel Catana、Huifen Chen、Jeff Ohren、Lisa A. Perrin

  DOI：10.1016/j.bmcl.2011.11.036

  日期：2012.1

  We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall. (C) 2011 Elsevier Ltd. All rights reserved.