(R)-1-(benzyl-methyl-amino)-3-chloropropan-2-ol | 866777-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-(benzyl-methyl-amino)-3-chloropropan-2-ol
• 英文别名: (2R)-1-[benzyl(methyl)amino]-3-chloropropan-2-ol
• CAS: 866777-92-6
• 化学式: C₁₁H₁₆ClNO
• 分子量: 213.707
• InChiKey: LLOYZOMZGJKFCZ-NSHDSACASA-N

物化性质

• 沸点：
  312.3±32.0 °C(Predicted)
• 密度：
  1.134±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-1-(benzyl-methyl-amino)-3-chloropropan-2-ol 、 二碳酸二叔丁酯 在 氢气 、 palladium(II) hydroxide 作用下， 以 乙酸乙酯 为溶剂， 生成 ((R)-3-chloro-2-hydroxy-propyl)-methyl-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT4 receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation

  摘要：

  Utilization of Theravance's multivalent approach to drug discovery towards 5-HT4 receptor agonists with a focus on identification of neutral (non-charged at physiological pH) secondary binding groups is described. Optimization of a quinolone-tropane primary binding group with a chiral 2-propanol linker to a range of neutral secondary binding group motifs, for binding affinity and functional potency at the 5-HT4 receptor, selectivity over the 5-HT3 receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, afforded velusetrag (TD-5108). Velusetrag has achieved proof-of-concept in patients with chronic idiopathic constipation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.051
• 作为产物：
  描述：

  左旋环氧氯丙烷 、 N-甲基苄胺 以 乙醇 、 四氢呋喃 、 水 为溶剂， 生成 (R)-1-(benzyl-methyl-amino)-3-chloropropan-2-ol
  参考文献：
  名称：

  Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT4 receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation

  摘要：

  Utilization of Theravance's multivalent approach to drug discovery towards 5-HT4 receptor agonists with a focus on identification of neutral (non-charged at physiological pH) secondary binding groups is described. Optimization of a quinolone-tropane primary binding group with a chiral 2-propanol linker to a range of neutral secondary binding group motifs, for binding affinity and functional potency at the 5-HT4 receptor, selectivity over the 5-HT3 receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, afforded velusetrag (TD-5108). Velusetrag has achieved proof-of-concept in patients with chronic idiopathic constipation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.051

文献信息

• Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
  申请人：Marquess Daniel

  公开号：US20050228014A1

  公开（公告）日：2005-10-13

  The invention provides novel quinolinone-carboxamide 5-HT 4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds.

  这项发明提供了新型喹诺酮-羧酰胺5-HT4受体激动剂化合物。该发明还提供包含这些化合物的药物组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。
• QUINOLINONE-CARBOXAMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS
  申请人：Marquess Daniel

  公开号：US20100285519A1

  公开（公告）日：2010-11-11

  The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds of Formula (I). The invention also provides pharmaceutical compositions comprising such compounds, the use such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds. Wherein; R 1 is hydrogen, halo, hydroxy, C 1-4 alkyl, or C 1-4 alkoxy; R 2 is C 3-4 alkyl, or C 3-6 cycloalkyl; R 3 is hydrogen or C 1-3 alkyl: R 4 is S(O) 2 R 6 or C(O)R 7 ; R 5 is hydrogen, C 1-3 alkyl, C 2-3 alkyl substituted with —OH or C 1-3 alkoxy, or —CH 2 -pyrydyl; R 6 is C 1-3 alkyl; or R 5 and R 6 taken together from C 3-4 alkylenyl; and R 7 is hydrogen, C 1-3 alkyl, or pyrydyl; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof.

  该发明提供了公式（I）的新型喹啉酮-羧酰胺5-HT4受体激动剂化合物。该发明还提供了包括这些化合物的制药组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。其中，R1为氢、卤素、羟基、C1-4烷基或C1-4烷氧基；R2为C3-4烷基或C3-6环烷基；R3为氢或C1-3烷基；R4为S（O）2R6或C（O）R7；R5为氢、C1-3烷基、C2-3烷基取代的-OH或C1-3烷氧基，或-CH2-吡啶基；R6为C1-3烷基；或R5和R6一起形成C3-4烷基亚乙基；R7为氢、C1-3烷基或吡啶基；或其药学上可接受的盐、溶剂或立体异构体。
• Quinolinone-carboxamide compounds as 5-HT4, receptor agonists
  申请人：Marquess Daniel

  公开号：US20080176895A1

  公开（公告）日：2008-07-24

  The invention provides novel quinolinone-carboxamide 5-HT 4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds.

  这项发明提供了新型的喹诺酮-羧酰胺5-HT4受体激动剂化合物。该发明还提供了包括这种化合物的制药组合物，使用这种化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这种化合物的过程和中间体。
• Quinolinone-carboxamide compounds as 5-HT, receptor agonists
  申请人：Marquess Daniel

  公开号：US20070270457A1

  公开（公告）日：2007-11-22

  The invention provides novel quinolinone-carboxamide 5-HT 4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds.

  该发明提供了新型的喹诺酮-羧酰胺5-HT4受体激动剂化合物。该发明还提供了包含这些化合物的药物组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。
• [EN] QUINOLINONE-CARBOXAMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS<br/>[FR] COMPOSES DE QUINOLINONE-CARBOXAMIDE EN TANT QU'AGONISTES DU RECEPTEUR DE 5-HT4
  申请人：THERAVANCE INC

  公开号：WO2005100350A1

  公开（公告）日：2005-10-27

  The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds of Formula (I). The invention also provides pharmaceutical compositions comprising such compounds, the use such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds. Wherein; R1 is hydrogen, halo, hadroxy, C1-4 alkyl, or C1-4 alkoxy; R2 is C3-4 alkyl, or C3-6 cycloakyl; R3 is hydrogen or C1-3 alkyl: R4 is ―S(O)2 R6 or―C(O)R7; R5 is hydrogen, C1-3alkyl, C2-3 alkyl subtituted with -OH or C1-3 alkoxy, or―CH2―pyrydyl; R6 is C1-3 alkyl; or R5 and R6 taken together from C3-4 alkylenyl; and R7 is hydrogen, C1-3alkyl, or pyrydyl; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof.

  本发明提供了公式（I）的新型喹诺酮-羧酰胺5-HT4受体激动剂化合物。本发明还提供了包含这些化合物的制药组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病，以及用于制备这些化合物的过程和中间体。其中；R1是氢，卤素，羟基，C1-4烷基或C1-4氧基烷基; R2是C3-4烷基或C3-6环烷基; R3是氢或C1-3烷基：R4是-S（O）2R6或-C（O）R7; R5是氢，C1-3烷基，C2-3烷基取代-OH或C1-3氧基烷基，或-CH2-pyrydyl; R6是C1-3烷基; 或R5和R6一起形成C3-4烷基亚烷基; R7是氢，C1-3烷基或pyrydyl; 或其药学上可接受的盐或溶剂或立体异构体。