methyl 2-[[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoyl]amino]acetate | 900183-91-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-[[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoyl]amino]acetate
• CAS: 900183-91-7
• 化学式: C₂₂H₂₄N₂O₅
• 分子量: 396.443
• InChiKey: CFOWPJCRJVUYMP-LJQANCHMSA-N

物化性质

• 沸点：
  613.0±40.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-[[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoyl]amino]acetate 在 哌啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 (R)-2-乙基-哌嗪
  参考文献：
  名称：

  Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1H-benzimidazoles

  摘要：

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).

  DOI：

  10.1021/jm060065y
• 作为产物：
  描述：

  甘氨酸甲酯盐酸盐 、 Fmoc-D-2-氨基丁酸 在 N-羟基-7-氮杂苯并三氮唑 、 PS-carbodiimide 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以62%的产率得到methyl 2-[[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoyl]amino]acetate
  参考文献：
  名称：

  Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1H-benzimidazoles

  摘要：

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).

  DOI：

  10.1021/jm060065y

文献信息

• Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1<i>H</i>-benzimidazoles
  作者：Vassil I. Ognyanov、Chenera Balan、Anthony W. Bannon、Yunxin Bo、Celia Dominguez、Christopher Fotsch、Vijay K. Gore、Lana Klionsky、Vu V. Ma、Yi-Xin Qian、Rami Tamir、Xianghong Wang、Ning Xi、Shimin Xu、Dawn Zhu、Narender R. Gavva、James J. S. Treanor、Mark H. Norman

  DOI：10.1021/jm060065y

  日期：2006.6.1

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).