(2R)-(3-amino-2-fluoropropyl)(methyl)phosphinic acid

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 英文名称: (2R)-(3-amino-2-fluoropropyl)(methyl)phosphinic acid
• 英文别名: [(2R)-3-amino-2-fluoropropyl]-methylphosphinic acid
• 化学式: C₄H₁₁FNO₂P
• 分子量: 155.109
• InChiKey: QSEZFOAWAVHOBH-SCSAIBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 以 二氯甲烷 、 甲醇 、 水 为溶剂， 以720 mg的产率得到(2R)-(3-amino-2-fluoropropyl)(methyl)phosphinic acid
  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

• (Aminopropyl)methylphosphinic acids
  申请人：AstraZeneca AB

  公开号：US06596711B1

  公开（公告）日：2003-07-22

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

  具有亲和力与一个或多个GABAB受体的化合物I的新型化合物，除了i)（3-氨基-2-羟基丙基）甲基膦酸的外消旋体；ii)（S）-（3-氨基-2-羟基丙基）甲基膦酸；iii)（R）-（3-氨基-2-羟基丙基）甲基膦酸；iv)（3-氨基-2-羟基丙基）二氟甲基膦酸；和v)（3-氨基-2-氧代丙基）甲基膦酸，其药学上可接受的盐，溶剂化合物和立体异构体，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以及在治疗中使用这些活性化合物的用途。
• Synthesis and Pharmacological Evaluation of Novel γ-Aminobutyric Acid Type B (GABA_B) Receptor Agonists as Gastroesophageal Reflux Inhibitors
  作者：Christer Alstermark、Kosrat Amin、Sean R. Dinn、Thomas Elebring、Ola Fjellström、Kevin Fitzpatrick、William B. Geiss、Johan Gottfries、Peter R. Guzzo、James P. Harding、Anders Holmén、Mohit Kothare、Anders Lehmann、Jan P. Mattsson、Karolina Nilsson、Gunnel Sundén、Marianne Swanson、Sverker von Unge、Alex M. Woo、Michael J. Wyle、Xiaozhang Zheng

  DOI：10.1021/jm701425k

  日期：2008.7.1

  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.