(2S,3'S)-2-methyl[1,3']bipyrrolidinyl | 1146611-63-3

• 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: (2S,3'S)-2-methyl[1,3']bipyrrolidinyl
• 英文别名: 2(2S)-methyl-[1,3'(3S)]bipyrrolidinyl；(2S,3'S)-2-Methyl-[1,3]bipyrrolidinyl；(2S)-2-methyl-1-[(3S)-pyrrolidin-3-yl]pyrrolidine
• CAS: 1146611-63-3
• 化学式: C₉H₁₈N₂
• 分子量: 154.255
• InChiKey: KHAUVQIIEQSBGB-IUCAKERBSA-N

物化性质

• 沸点：
  216.9±8.0 °C(Predicted)
• 密度：
  0.975±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-氯-2-甲基-3-硝基吡啶 、 (2S,3'S)-2-methyl[1,3']bipyrrolidinyl 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 以87%的产率得到(2S,3'S)-2-methyl-1'-(6-methyl-5-nitro-pyridin-2-yl)-[1,3']bipyrrolidinyl
  参考文献：
  名称：

  Identification and profiling of 3,5-dimethyl-isoxazole-4-carboxylic acid [2-methyl-4-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)phenyl] amide as histamine H3 receptor antagonist for the treatment of depression

  摘要：

  Lead optimization guided by histamine H-3 receptor (H3R) affinity and calculated physico-chemical properties enabled simultaneous improvement in potency and PK properties leading to the identification of a potent, selective, devoid of hERG issues, orally bioavailable, and CNS penetrable H3R antagonist/ inverse agonist 3h. The compound was active in forced-swimming tests suggesting its potential therapeutic utility as an anti-depressive agent. This Letter further includes its cardiovascular and neuropsychological/behavioral safety assessments. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.081

文献信息

• [EN] SUBSTITUTED N-HETEROARYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] BIPYRROLIDINES N-HÉTÉROARYL SPIROLACTAME SUBSTITUÉES, PROCÉDÉ DE PRÉPARATION ET USAGE THÉRAPEUTIQUE ASSOCIÉS
  申请人：SANOFI SA

  公开号：WO2011143148A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N-heteroaryl spirolactam bipyrrolidines of formula ( Wherein R1, R2, Q1, Q2, Q3, Q4, X, m, n, p and s are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-heteroaryl spirolactam bipyrrolidines of formula (I) and intermediates therefor.

  本发明公开并声明了一系列式（其中R1、R2、Q1、Q2、Q3、Q4、X、m、n、p和s如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的疾病在内的多种受H3受体调节的疾病中有用作药用剂，此外，本发明还公开了制备式（I）的取代N-杂环烷基螺内酰胺双吡咯烷的方法及其中间体。
• [EN] SUBSTITUTED N-HETEROCYCLOALKYL BIPYRROLIDINYLPHENYL AMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] DÉRIVÉS DE N-HÉTÉROCYCLOALKYL-BIPYRROLIDINYLPHÉNYLAMIDE SUBSTITUÉS, PRÉPARATION ET UTILISATION THÉRAPEUTIQUE DE CEUX-CI
  申请人：SANOFI SA

  公开号：WO2011143161A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N- heterocycloalkyl bipyrrolidinylphenyl amide derivatives of formula (I). (Formula (I)) Wherein R, R1, R2, R3, R4, X, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-heterocycloalkyl bipyrrolidinylphenyl amide derivatives of formula (I) and intermediates therefor.

  本发明公开并声明了一系列式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物。其中R、R1、R2、R3、R4、X、m、n和p如本文所述。更具体地，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的疾病在内的多种受H3受体调节的疾病方面作为药用剂特别有用。此外，本发明还公开了制备式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物及其中间体的方法。
• [EN] SUBSTITUTED N-PHENYL-BIPYRROLIDINE CARBOXAMIDES AND THERAPEUTIC USE THEREOF<br/>[FR] CARBOXAMIDES DE N-PHÉNYL-BIPYRROLIDINE SUBSTITUÉS ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI AVENTIS

  公开号：WO2009052065A1

  公开（公告）日：2009-04-23

  The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I), Wherein R, R1, R2, R3 and R4 are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefor.

  本发明公开并声明了一系列式(I)的取代N-苯基-双吡咯烷羧酰胺，其中R、R1、R2、R3和R4如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在制药方面特别有用，尤其是在治疗和/或预防通过H3受体调节的各种疾病，包括与中枢神经系统相关的疾病。此外，本发明还公开了取代N-苯基-双吡咯烷羧酰胺及其中间体的制备方法。
• [EN] SUBSTITUTED N-HETEROARYL BIPYRROLIDINE CARBOXAMIDES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] CARBOXAMIDES DE N-HÉTÉROARYL-BIPYRROLIDINE SUBSTITUÉS, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI SA

  公开号：WO2011143162A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N-heteroaryl bipyrrolidine carboxamides of formula (I). Wherein R1 R2, R3, R4, Q1, Q2, Q3, Q4, X, m and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-heteroaryl bipyrrolidine carboxamides of formula (I) and intermediates therefor.

  本发明公开并声明了一系列代替N-杂环芳基双吡咯啉羧酰胺的化合物，其化学式为（I）。其中R1、R2、R3、R4、Q1、Q2、Q3、Q4、X、m和p如本文所述。更具体地说，本发明的化合物是H3受体的调节剂，因此可作为药物剂，特别是用于治疗和/或预防多种由H3受体调节的疾病，包括与中枢神经系统相关的疾病。此外，本发明还公开了制备化合物（I）的代替N-杂环芳基双吡咯啉羧酰胺及其中间体的方法。
• [EN] SUBSTITUTED N-PHENYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] BIPYRROLIDINES N-PHÉNYL SPIROLACTAME SUBSTITUÉES, PROCÉDÉ DE PRÉPARATION ET USAGE THÉRAPEUTIQUE ASSOCIÉS
  申请人：SANOFI SA

  公开号：WO2011143163A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N-phenyl spirolactam bipyrrolidines of formula (I). (Formula (I)) Wherein R1, R2, R3, R4, m, n, p and s are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-phenyl spirolactam bipyrrolidines of formula (I) and intermediates therefor.

  本发明披露并声明了一系列代替N-苯基螺内酰胺双吡咯烷酮的化合物，其化学式为 (I)。其中，R1、R2、R3、R4、m、n、p 和 s 如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在治疗和/或预防多种由H3受体调节的疾病中，尤其是与中枢神经系统相关的疾病中，可作为药用剂。此外，本发明还披露了制备化合物 (I) 的代替N-苯基螺内酰胺双吡咯烷酮以及其中间体的方法。