(S)-<2-<(2(R)-hydroxypropyl)amino>-1-methylethyl>carbamic acid 1,1-dimethylethyl ester | 170568-61-3

• 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: (S)-<2-<(2(R)-hydroxypropyl)amino>-1-methylethyl>carbamic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl (S)-1-[(R)-2-hydroxypropylamino]propan-2-ylcarbamate；tert-butyl N-[(2S)-1-[[(2R)-2-hydroxypropyl]amino]propan-2-yl]carbamate
• CAS: 170568-61-3
• 化学式: C₁₁H₂₄N₂O₃
• 分子量: 232.323
• InChiKey: HBXZQKVBLPMNCI-DTWKUNHWSA-N

物化性质

• 熔点：
  77-78 °C
• 沸点：
  364.4±22.0 °C(Predicted)
• 密度：
  1.012±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-<2-<(2(R)-hydroxypropyl)amino>-1-methylethyl>carbamic acid 1,1-dimethylethyl ester 在 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 tert-butyl 7-chloro-5-[(3S,5S)-3,5-dimethylpiperazine-1-carbonyl]-4H-imidazo[1,5-a]quinoxaline-3-carboxylate
  参考文献：
  名称：

  Piperazine Imidazo[1,5-a]quinoxaline Ureas as High-Affinity GABA_A Ligands of Dual Functionality

  摘要：

  A series of imidazo[1,5-alpha]quinoxaline piperazine ureas appended with a tert-butyl ester side chain at the 3-position was developed. Analogues within this series have high affinity for the gamma-aminobutyric acid A (GABA(A))/benzodiazepine receptor complex with efficacies ranging from inverse agonists to full agonists. Many analogues were found to be partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Uniquely, a number of these analogues were found to have a bell-shaped dose-response profile in the alpha(1)beta(2)gamma(2) subtype as determined by whole cell patch-clamp technique, where in vitro efficacy was found to decrease with increasing drug concentration. Many of the compounds from this series were effective in antagonizing metrazole-induced seizures, consistent with anticonvulsant and possibly anxiolytic activity. Additionally, several analogues were also effective in lowering cGMP levels (to control values) after applied stress, also consistent with anxiolytic-like properties. The most effective compounds in these screens were also active in animal models of anxiety such as the Vogel and Geller assays. The use of the piperazine substituent allowed for excellent drug levels and a long duration of action in the central nervous system for many of the quinoxalines, as determined by ex vivo assay. Pharmacokinetic analysis of several compounds indicated excellent oral bioavailability and a reasonable half-life in rats. From this series emerged two partial agonists (55, 91) which had good activity in anxiolytic models, acceptable pharmacokinetics, and minimal benzodiazepine-type side effects.

  DOI：

  10.1021/jm9801307
• 作为产物：
  描述：

  (S)-<2-<(2(R)-hydroxypropyl)amino>-1-methyl-2-oxoethyl>carbamic acid 1,1-dimethylethyl ester 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以75%的产率得到(S)-<2-<(2(R)-hydroxypropyl)amino>-1-methylethyl>carbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Piperazine Imidazo[1,5-a]quinoxaline Ureas as High-Affinity GABA_A Ligands of Dual Functionality

  摘要：

  A series of imidazo[1,5-alpha]quinoxaline piperazine ureas appended with a tert-butyl ester side chain at the 3-position was developed. Analogues within this series have high affinity for the gamma-aminobutyric acid A (GABA(A))/benzodiazepine receptor complex with efficacies ranging from inverse agonists to full agonists. Many analogues were found to be partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Uniquely, a number of these analogues were found to have a bell-shaped dose-response profile in the alpha(1)beta(2)gamma(2) subtype as determined by whole cell patch-clamp technique, where in vitro efficacy was found to decrease with increasing drug concentration. Many of the compounds from this series were effective in antagonizing metrazole-induced seizures, consistent with anticonvulsant and possibly anxiolytic activity. Additionally, several analogues were also effective in lowering cGMP levels (to control values) after applied stress, also consistent with anxiolytic-like properties. The most effective compounds in these screens were also active in animal models of anxiety such as the Vogel and Geller assays. The use of the piperazine substituent allowed for excellent drug levels and a long duration of action in the central nervous system for many of the quinoxalines, as determined by ex vivo assay. Pharmacokinetic analysis of several compounds indicated excellent oral bioavailability and a reasonable half-life in rats. From this series emerged two partial agonists (55, 91) which had good activity in anxiolytic models, acceptable pharmacokinetics, and minimal benzodiazepine-type side effects.

  DOI：

  10.1021/jm9801307

文献信息

• 11-Beta HSD 1 inhibitors
  申请人：Xiang Shaoyun Jason

  公开号：US20070219198A1

  公开（公告）日：2007-09-20

  This invention relates to inhibiting 11βHSD1.

  该发明涉及抑制11βHSD1。
• 11-Beta HSD1 Inhibitors
  申请人：Xiang Jason Shaoyun

  公开号：US20100029648A1

  公开（公告）日：2010-02-04

  This invention relates to inhibiting 11βHSD1.

  本发明涉及抑制11βHSD1。
• 11-beta HSD1 inhibitors
  申请人：Wyeth

  公开号：US07632838B2

  公开（公告）日：2009-12-15

  This invention relates to inhibiting 11βHSD1.

  本发明涉及抑制11βHSD1的方法。
• WO2007/92435
  申请人：——

  公开号：——

  公开（公告）日：——
• US7632838B2
  申请人：——

  公开号：US7632838B2

  公开（公告）日：2009-12-15