4-(2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamine

• 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: 4-(2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamine
• 英文别名: 4-[3-(2-Methylpyrrolidin-1-yl)pyrrolidin-1-yl]aniline
• 化学式: C₁₅H₂₃N₃
• 分子量: 245.368
• InChiKey: ADEHHNQEZMQYGS-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：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-四氢呋喃甲酸 、 4-(2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]oxolane-2-carboxamide
  参考文献：
  名称：

  Discovery of a potent, selective, and orally bioavailable histamine H3 receptor antagonist SAR110068 for the treatment of sleep–wake disorders

  摘要：

  Previous studies have shown that compound 1 displayed high affinity towards histamine H-3 receptor (H3R), (human (h-H3R), K-i = 8.6 nM, rhesus monkey (rh-H3R), K-i = 1.2 nM, and rat (r-H3R), K-i = 16.5 nM), but exhibited high affinity for hERG channel. Herein, we report the discovery of a novel, potent, and highly selective H3R antagonist/inverse agonist 5a(SS) (SAR110068) with acceptable hERG channel selectivity and desirable pharmacological and pharmacokinetic properties through lead optimization sequence. The significant awakening effects of 5a(SS) on sleep-wake cycles studied by using EEG recording in rats during their light phase support its potential therapeutic utility in human sleep-wake disorders. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.006
• 作为产物：
  描述：

  2-甲基吡咯烷 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 4-(2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamine
  参考文献：
  名称：

  发现作为治疗肥胖症的有效和选择性组胺H 3受体拮抗剂的芳基脲和芳基酰胺（第一部分）

  摘要：

  通过优化HTS铅作为选择性组胺H 3受体（H 3 R）拮抗剂，获得了一系列结构新颖的芳基脲。探索了SAR，获得的数据为进一步优化奠定了起点和基础。如化合物2l，5b，5d和5e所示，最有效的工具化合物在体外人-H 3 R FLIPR分析和恒河猴H 3 R结合分析中显示出亚纳摩尔范围的拮抗力。

  DOI：

  10.1016/j.bmcl.2013.03.080

文献信息

• [EN] SUBSTITUTED N-PHENYL-BIPYRROLIDINE UREAS AND THERAPEUTIC USE THEREOF<br/>[FR] URÉES DE N-PHÉNYL-BIPYRROLIDINE SUBSTITUÉES ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI AVENTIS

  公开号：WO2009052068A1

  公开（公告）日：2009-04-23

  The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine ureas of formula (I) 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 ureas and intermediates therefor.

  本发明披露并声明一系列取代的N-苯基双吡咯啉脲（式（I）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，因此在医药制剂中特别用于治疗和/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，本发明还披露了制备取代的N-苯基双吡咯啉脲及其中间体的方法。
• SUBSTITUTED N-PHENYL-BIPYRROLIDINE CARBOXAMIDES AND THERAPEUTIC USE THEREOF
  申请人：CZECHTIZKY Werngard

  公开号：US20120065234A1

  公开（公告）日：2012-03-15

  The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I). wherein R, R 1 , R 2 , R 3 and R 4 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.

  本发明揭示和声明了一系列式（I）的取代N-苯基双吡咯烷羧酰胺化合物，其中R、R1、R2、R3和R4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有关的多种受H3受体调节的疾病方面，尤其是作为药物剂量非常有用。此外，本发明还揭示了取代N-苯基双吡咯烷羧酰胺化合物的制备方法及其中间体。
• Substituted N-phenyl-bipyrrolidine carboxamides and therapeutic use thereof
  申请人：Sanofi

  公开号：US08088808B2

  公开（公告）日：2012-01-03

  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.

  本发明公开和声明了一系列化合物，其为式(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受体的调节剂，因此在治疗和/或预防包括与中枢神经系统有关的多种H3受体调节的疾病中，特别是作为药物剂量是有用的。此外，本发明还公开了制备取代N-苯基双吡咯烷羧酰胺及其中间体的方法。
• SUBSTITUTED N-PHENYL-BIPYRROLIDINE UREAS AND THERAPEUTIC USE THEREOF
  申请人：CZECHTIZKY Werngard

  公开号：US20100173908A1

  公开（公告）日：2010-07-08

  The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine ureas of formula (I). Wherein R, R 1 , R 2 , R 3 , R 4 and R 5 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 ureas and intermediates therefor.

  本发明公开和声明了一系列公式（I）的取代N-苯基双吡咯烷脲。其中R、R1、R2、R3、R4和R5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有关的多种H3受体调控的疾病中，尤其是作为药物剂量非常有用。此外，本发明还公开了取代N-苯基双吡咯烷脲及其中间体的制备方法。
• Substituted tetrahydropyran spiro pyrrolidinone and piperidinone, preparation and therapeutic use thereof
  申请人：Sanofi

  公开号：US08217052B2

  公开（公告）日：2012-07-10

  The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I): wherein R1, R2, 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, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefore are disclosed.

  本公开涉及一系列取代的N-苯基双吡咯烷羧酰胺化合物，其化学式为(I)：其中R1、R2、m、n和p如本文所述。更具体地，本发明化合物是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，特别是与中枢神经系统相关的疾病中，作为药物剂量是有用的。此外，还公开了取代的N-苯基双吡咯烷羧酰胺化合物的制备方法及其中间体。