2-(2S)-methyl-1'-(3-methyl-4-nitro-phenyl)-[1,3'(3'S)]bipyrrolidinyl | 1146415-67-9

• 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: 2-(2S)-methyl-1'-(3-methyl-4-nitro-phenyl)-[1,3'(3'S)]bipyrrolidinyl
• 英文别名: (2S,3'S)-2-methyl-1'-(3-methyl-4-nitro-phenyl)-[1,3']bipyrrolidinyl；(2S)-2-methyl-1-[(3S)-1-(3-methyl-4-nitrophenyl)pyrrolidin-3-yl]pyrrolidine
• CAS: 1146415-67-9
• 化学式: C₁₆H₂₃N₃O₂
• 分子量: 289.378
• InChiKey: HHAUFTJSDMPHKG-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2S)-methyl-1'-(3-methyl-4-nitro-phenyl)-[1,3'(3'S)]bipyrrolidinyl 在 钯 甲醇 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以to afford 0.65 g (90%) of the title compound的产率得到2-methyl-4-(2-(2S)-methyl-[1,3'(3'S)]bipyrrolidinyl-1'-yl)-phenylamine
  参考文献：
  名称：

  SUBSTITUTED N-PHENYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF

  摘要：

  本公开涉及一系列取代N-苯基螺内酯双吡咯啉化合物，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/或预防包括与中枢神经系统相关的多种疾病在内的H3受体调节的疾病中作为药物剂量是有用的。此外，本公开还涉及制备取代N-苯基螺内酯双吡咯啉化合物（I）及其中间体的方法。

  公开号：

  US20130059874A1
• 作为产物：
  描述：

  5-氟-2-硝基甲苯 、 (2S,3'S)-2-methyl[1,3']bipyrrolidinyl dihydrochloride 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 生成 2-(2S)-methyl-1'-(3-methyl-4-nitro-phenyl)-[1,3'(3'S)]bipyrrolidinyl
  参考文献：
  名称：

  Synthesis, characterization, and biological assessment of the four stereoisomers of the H3 receptor antagonist 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3′]bipyrrolidinyl-1′-yl)phenyl]benzamide

  摘要：

  This Letter describes the asymmetric synthesis of the four stereoisomers (8a-8d) of a potent and highly selective histamine H-3 receptor (H3R) antagonist, 5-fluoro-2-methyl-N-[2-methyl-4-(2methyl[1,3']bipyrrolidinyl-1'-yl)phenyl]benzamide (1). The physico-chemical properties, in vitro H3R affinities and ADME of 8a-8d were determined. Stereoisomer 8c (2S, 3'S) displayed superior in vitro H3R affinity over other three stereoisomers and was selected for further profiling in in vivo PK and drug safety. Compound 8c exhibited excellent PK properties with high exposure, desired brain to plasma ratio and reasonable brain half life. However, all stereoisomers showed similar unwanted hERG affinities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.068

文献信息

• [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。
• [EN] SUBSTITUTED TETRAHYDROPYRAN SPIRO PYRROLIDINONE AND PIPERIDINONE, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] PYRROLIDINONE ET PIPÉRIDINONE SPIRO À SUBSTITUTION DE TÉTRAHYDROPYRANNE, SA PREPARATION ET SON UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI AVENTIS

  公开号：WO2010065798A1

  公开（公告）日：2010-06-10

  The present invention discloses and claims 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, this invention also discloses methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefor.

  本发明披露并声称一系列式（I）的取代N-苯基双吡咯烷羧酰胺化合物，其中R1、R2、m、n和p如本文所述。更具体地说，本发明的化合物是H3受体调节剂，因此在制药剂中非常有用，特别是在治疗和/或预防由H3受体调节的各种疾病中，包括与中枢神经系统相关的疾病。此外，本发明还披露了取代N-苯基双吡咯烷羧酰胺及其中间体的制备方法。
• [EN] SUBSTITUTED N-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 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。