Tert-butyl 3-cyano-3-(2-methylpropyl)pyrrolidine-1-carboxylate | 944142-21-6

• 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: Tert-butyl 3-cyano-3-(2-methylpropyl)pyrrolidine-1-carboxylate
• CAS: 944142-21-6
• 化学式: C₁₄H₂₄N₂O₂
• 分子量: 252.357
• InChiKey: NNPZTZUYDFENDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  53.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl 3-cyano-3-(2-methylpropyl)pyrrolidine-1-carboxylate 在 三异丁基铝 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain

  摘要：

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.020
• 作为产物：
  描述：

  1-Boc-3-氰基吡咯烷 、 alkaline earth salt of/the/ methylsulfuric acid 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 Tert-butyl 3-cyano-3-(2-methylpropyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain

  摘要：

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.020

文献信息

• Organic Compounds
  申请人：Ehara Takeru

  公开号：US20090192148A1

  公开（公告）日：2009-07-30

  The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3,5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The compounds have the formula I′ wherein R1, R2, T, R3 and R4 areas defined in the specification.

  本发明涉及3,5-取代哌啶化合物，这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖肾素活性的疾病（=失调）；该类化合物用于制备治疗依赖肾素活性疾病的制剂；该类化合物用于治疗依赖肾素活性的疾病；包括3,5-取代哌啶化合物的制药配方和/或包括给予3,5-取代哌啶化合物的治疗方法，以及制造3,5-取代哌啶化合物的新型中间体和部分合成步骤。该化合物的式子为I'，其中R1、R2、T、R3和R4在规范中有定义。
• 3 , 5-substitued piperidine compounds as renin inhibitors
  申请人：Novartis AG

  公开号：EP2420491A1

  公开（公告）日：2012-02-22

  The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (= disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3, 5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The compounds (which can also be present as salts) have the formula I' wherein R1, R2, T, R3, R4, R7 and R8 are as defined in the specification and R6 is OH.

  本发明涉及3,5-取代的哌啶化合物，这些化合物用于温血动物的诊断和治疗，特别是用于治疗依赖于肾素活性的疾病（=紊乱）；使用该类化合物制备药物制剂，用于治疗依赖于肾素活性的疾病；该类化合物在治疗依赖于肾素活性的疾病中的用途；包含 3,5-取代的哌啶化合物的药物制剂，和/或包括施用 3,5-取代的哌啶化合物的治疗方法，3,5-取代的哌啶化合物的制造方法，及其合成的新型中间体和部分步骤。 这些化合物（也可以以盐的形式存在）具有式 I' 其中 R1、R2、T、R3、R4、R7 和 R8 如说明书中所定义，R6 为 OH。
• US8129411B2
  申请人：——

  公开号：US8129411B2

  公开（公告）日：2012-03-06
• [EN] 3 , 5-SUBSTITGUED PIPERIDINE COMPOUNDS AS RENIN INHIBITORS<br/>[FR] DÉRIVÉS DE PIPÉRIDINE 3,5-SUBSTITUÉS EN TANT QU'INHIBITEURS DE RÉNINE
  申请人：NOVARTIS AG

  公开号：WO2007077005A1

  公开（公告）日：2007-07-12

  [EN] The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (= disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3, 5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The preferred compounds (which can also be present as salts) have the formula (I'), wherein R1 , R2, T, R3 and R4 are as defined in the specification.
  [FR] La présente invention concerne des dérivés de pipéridine 3,5-substitués, ces composés pouvant être employés dans le diagnostic et le traitement thérapeutique d'un animal à sang chaud, en particulier dans le traitement d'une maladie (= trouble) qui dépend de l'activité de la rénine ; l'utilisation d'un composé de cette classe dans l'élaboration d'une formule pharmaceutique destinée au traitement d'une maladie qui dépend de l'activité de la rénine ; l'utilisation d'un composé de cette classe dans le traitement d'une maladie qui dépend de l'activité de la rénine ; les formules pharmaceutiques comprenant un dérivé de pipéridine 3,5-substitué, et/ou une méthode de traitement comprenant l'administration d'un dérivé de pipéridine 3,5-substitué, une méthode de fabrication d'un dérivé de pipéridine 3,5-substitué, et de nouveaux intermédiaires et étapes partielles de la synthèse d'un tel dérivé. Les composés préférés (qui peuvent également être présents sous forme de sels) sont de formule (I'), R1, R2, T, R3 et R4 étant tels que définis dans la description de l'invention.
• Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain
  作者：Matthew C. Lucas、Robert J. Weikert、David S. Carter、Hai-Ying Cai、Robert Greenhouse、Pravin S. Iyer、Clara J. Lin、Eun Kyung Lee、Ann Marie Madera、Amy Moore、Kerem Ozboya、Ryan C. Schoenfeld、Sandra Steiner、Yansheng Zhai、Stephen M. Lynch

  DOI：10.1016/j.bmcl.2010.07.020

  日期：2010.9

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.