ethyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-2-fluoropropanoate | 344413-71-4

• 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: ethyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-2-fluoropropanoate
• 英文别名: ethyl 3-[diethoxymethyl(ethoxy)phosphoryl]-2-fluoropropanoate
• CAS: 344413-71-4
• 化学式: C₁₂H₂₄FO₆P
• 分子量: 314.291
• InChiKey: XPNWDUQCYCPPMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-2-fluoropropanoate 在 ammonium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 以27%的产率得到ethyl (3-amino-2-fluoro-3-oxopropyl)(diethoxymethyl)phosphinate
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Novel γ-Aminobutyric Acid Type B (GABA_B) Receptor Agonists as Gastroesophageal Reflux Inhibitors

  摘要：

  We have previously demonstrated that the prototypical GABA(B) receptor agonist baclofen inhibits transient lower esophageal sphincter relaxations (TLESRs), the most important mechanism for gastroesophageal reflux. Thus, GABAB agonists could be exploited for the treatment of gastroesophageal reflux disease. However, baclofen, which is used as an antispastic agent, and other previously known GABAB agonists can produce CNS side effects such as sedation, dizziness, nausea, and vomiting at higher doses. We now report the discovery of atypical GABAB agonists devoid of classical GABAB agonist related CNS side effects at therapeutic doses and the optimization of this type of compound for inhibition of TLESRs, which has resulted in a candidate drug (R)-7 (AZD3355) that is presently being evaluated in man.

  DOI：

  10.1021/jm701425k
• 作为产物：
  描述：

  2-氟代丙烯酸乙酯 、 ethyl diethoxymethylphosphinate 在 六甲基二硅氮烷 作用下， 反应 74.0h， 以57%的产率得到ethyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-2-fluoropropanoate
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Novel γ-Aminobutyric Acid Type B (GABA_B) Receptor Agonists as Gastroesophageal Reflux Inhibitors

  摘要：

  We have previously demonstrated that the prototypical GABA(B) receptor agonist baclofen inhibits transient lower esophageal sphincter relaxations (TLESRs), the most important mechanism for gastroesophageal reflux. Thus, GABAB agonists could be exploited for the treatment of gastroesophageal reflux disease. However, baclofen, which is used as an antispastic agent, and other previously known GABAB agonists can produce CNS side effects such as sedation, dizziness, nausea, and vomiting at higher doses. We now report the discovery of atypical GABAB agonists devoid of classical GABAB agonist related CNS side effects at therapeutic doses and the optimization of this type of compound for inhibition of TLESRs, which has resulted in a candidate drug (R)-7 (AZD3355) that is presently being evaluated in man.

  DOI：

  10.1021/jm701425k

文献信息

• [EN] NEW AMINOPROPYLPHOSPHINIC ACIDS<br/>[FR] NOUVEAUX ACIDES AMINOPROPYLPHOSPHINIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2001042252A1

  公开（公告）日：2001-06-14

  Novel compounds of formula (I), with the exception of i) the racemate of (3-amino-2-hydroxypropyl)phosphinic acid; and ii) (2R/S, 3R)-(3-amino-2-hydroxybutyl)phosphinic acid, having affinity to one or more GABAB receptors, their pharmaceutically acceptable salts, solvates and stereoisomers, as well as processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds and the use of said active compounds in therapy.

  公式（I）的新化合物，除了i）（3-氨基-2-羟基丙基）膦酸的外消旋体；和ii）（2R / S，3R）-（3-氨基-2-羟基丁基）膦酸，具有亲和力到一个或多个GABAB受体，它们的药学上可接受的盐，溶剂和立体异构体，以及它们的制备过程，含有这些治疗活性化合物的制药组合物和在治疗中使用这些活性化合物。
• New aminopropylphosphinic acids
  申请人：Elebring Thomas

  公开号：US20050137414A1

  公开（公告）日：2005-06-23

  Novel compounds of formula I, with the exception of i) the racemate of (3-amino-2-hydroxypropyl)phosphinic acid; and ii) (2R/S, 3R)-(3-amino-2-hydroxybutyl)phosphinic acid, having affinity to one or more GABA B receptors, their pharmaceutically acceptable salts, solvates and stereoisomers, as well as processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds and the use of said active compounds in therapy.

  公式I的新化合物，除了i) (3-氨基-2-羟基丙基)磷酸缩氨酸的外消旋体;和ii) (2R / S，3R) - (3-氨基-2-羟基丁基)磷酸缩氨酸，具有与一个或多个GABAB受体亲和力，它们的药学上可接受的盐，溶剂和立体异构体，以及它们的制备过程，含有所述治疗活性化合物的药物组合物以及在治疗中使用所述活性化合物的用途。
• Aminopropylphosphinic acids
  申请人：AstraZeneca AB

  公开号：US06576626B2

  公开（公告）日：2003-06-10

  Novel compounds of formula I, with the exception of i) the racemate of (3-amino-2-hydroxypropyl)phosphinic acid; and ii) (2R/S, 3R)-(3-amino-2-hydroxybutyl)phosphinic acid, having affinity to one or more GABAB receptors, their pharmaceutically acceptable salts, solvates and stereoisomers, as well as processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds and the use of said active compounds in therapy

  具有亲和力于一个或多个GABAB受体的化合物I公式的新颖化合物，除了i) (3-氨基-2-羟基丙基)磷酸酰胺的外消旋体; 和ii) (2R / S, 3R) - (3-氨基-2-羟基丁基)磷酸酰胺，以及其药学上可接受的盐，溶剂合物和立体异构体，以及制备它们的过程，包含所述治疗活性化合物的制药组合物和在治疗中使用所述活性化合物的用途。
• New use of GabaB receptor agonists
  申请人：Lehmann Anders

  公开号：US20070021393A1

  公开（公告）日：2007-01-25

  Novel compounds of formula I, with the exception of i) the racemate of (3-amino-2-hydroxypropyl)phosphinic acid; and ii) (2R/S, 3R)-(3-amino-2-hydroxybutyl)phosphinic acid, having affinity to one or more GABA B receptors, their pharmaceutically acceptable salts; solvates and stereoisomers, as well as processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds and the use of said active compounds in therapy.

  公式I的新化合物，除了i) (3-氨基-2-羟基丙基)膦酸的外消旋体；和ii) (2R/S，3R)-(3-氨基-2-羟基丁基)膦酸，具有对一个或多个GABAB受体的亲和力，它们的药学上可接受的盐；溶剂合物和立体异构体，以及它们的制备方法，含有上述治疗活性化合物的制药组合物和在治疗中使用的活性化合物。
• New Aminopropylphosphinic acids
  申请人：Elebring Thomas

  公开号：US20080146836A1

  公开（公告）日：2008-06-19

  Novel compounds of formula I, with the exception of i) the racemate of (3-amino-2-hydroxypropyl)phosphinic acid; and ii) (2R/S,3R)-(3-amino-2-hydroxybutyl)phosphinic acid, having affinity to one or more GABA B receptors, their pharmaceutically acceptable salts, solvates and stereoisomers, as well as processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds and the use of said active compounds in therapy.

  具有亲和力与一种或多种GABAB受体的式I的新化合物，除了i) (3-氨基-2-羟基丙基)磷酸肌醇盐的外消旋体; 和ii) (2R/S,3R)-(3-氨基-2-羟基丁基)磷酸肌醇盐，以及它们的药学上可接受的盐、溶剂和立体异构体，以及制备它们的过程，含有这些治疗活性化合物的制药组合物以及在治疗中使用这些活性化合物的用途。