ethyl [3-[N-(tert-butoxycarbonyl)amino]-2-oxopropyl](1,1-diethoxyethyl)phosphinate | 344413-77-0

• 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-[N-(tert-butoxycarbonyl)amino]-2-oxopropyl](1,1-diethoxyethyl)phosphinate
• 英文别名: tert-butyl 3-((1,1-diethoxyethyl)(ethoxy)phosphoryl)-2-oxopropylcarbamate；tert-butyl N-[3-[1,1-diethoxyethyl(ethoxy)phosphoryl]-2-oxopropyl]carbamate
• CAS: 344413-77-0
• 化学式: C₁₆H₃₂NO₇P
• 分子量: 381.406
• InChiKey: SUDUNMHGZWNROG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl [3-[N-(tert-butoxycarbonyl)amino]-2-oxopropyl](1,1-diethoxyethyl)phosphinate 在 盐酸 、 水 、 methyloxirane 作用下， 以 甲醇 为溶剂， 反应 26.0h， 以71%的产率得到(3-amino-2-oxopropyl)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
• 作为产物：
  描述：

  BOC-甘氨酸甲酯 、 1,1-二乙氧基-1-[乙氧基(甲基)磷基]乙烷 在 lithium diisopropyl amide 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 以85%的产率得到ethyl [3-[N-(tert-butoxycarbonyl)amino]-2-oxopropyl](1,1-diethoxyethyl)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

文献信息

• 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.
• US7034176B2
  申请人：——

  公开号：US7034176B2

  公开（公告）日：2006-04-25
• Development of a Continuous Flow Scale-Up Approach of Reflux Inhibitor AZD6906
  作者：Tomas Gustafsson、Henrik Sörensen、Fritiof Pontén

  DOI：10.1021/op200340c

  日期：2012.5.18

  Early scale-up work of a promising reflux inhibitor AZD6906 is described. Two steps of an earlier route were adapted to be performed in continuous flow to avoid issues related to batch procedures, resulting in a robust method with reduced cost of goods and improved product quality. Toxic and reactive reagents and starting materials could be handled in a flow regime, thereby allowing safer and more convenient reaction optimization and production.