S-{[(2R,3R)-3-(methoxymethyl)-1-(methoxymethyl)-4-oxo-azetidin-2-yl]methyl} thioacetate | 1835745-18-0

• 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: S-{[(2R,3R)-3-(methoxymethyl)-1-(methoxymethyl)-4-oxo-azetidin-2-yl]methyl} thioacetate
• 英文别名: S-[[(2R,3R)-3-(Methoxymethoxy)-1-(methoxymethyl)-4-oxo-2-azetidinyl]methyl] ethanethioate；S-[[(2R,3R)-3-(methoxymethoxy)-1-(methoxymethyl)-4-oxoazetidin-2-yl]methyl] ethanethioate
• CAS: 1835745-18-0
• 化学式: C₁₀H₁₇NO₅S
• 分子量: 263.315
• InChiKey: GOBCZSPAFIOYGR-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  溴代异丁烷 、 S-{[(2R,3R)-3-(methoxymethyl)-1-(methoxymethyl)-4-oxo-azetidin-2-yl]methyl} thioacetate 在 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 以125 mg的产率得到(3R,4R)-4-[(isobutylsulfanyl)methyl]-3-(methoxymethoxy)-1-(methoxymethyl)azetidin-2-one
  参考文献：
  名称：

  TW2016/9654

  摘要：

  公开号：
• 作为产物：
  描述：

  硫代乙酸 、 (3R,4S)-4-(hydroxymethyl)-3-(methoxymethoxy)-1-(methoxymethyl)azetidin-2-one 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以300 mg的产率得到S-{[(2R,3R)-3-(methoxymethyl)-1-(methoxymethyl)-4-oxo-azetidin-2-yl]methyl} thioacetate
  参考文献：
  名称：

  TW2016/9654

  摘要：

  公开号：

文献信息

• Pyridine derivative
  申请人：Astellas Pharma Inc.

  公开号：US10059720B2

  公开（公告）日：2018-08-28

  The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-[4-(substituted pyridine)-2-yl]methyl}-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.

  本发明要解决的问题是提供一种适用于药物组合物的化合物，特别是一种用于治疗夜尿症的药物组合物。 本发明者假定，抑制胎盘亮氨酸氨肽酶（P-LAP）（即能裂解 AVP 的氨肽酶）的夜间活性将维持和/或增加内源性 AVP 水平，从而增强抗利尿作用，这将有助于减少夜间排尿次数，并对抑制 P-LAP 的化合物进行了广泛研究。 结果，本发明人发现(2R)-3-氨基-2-[4-（取代的吡啶）-2-基]甲基}-2-羟基丙酸衍生物具有极佳的 P-LAP 抑制活性。本发明者评估了水负荷大鼠的抗利尿作用，发现这些化合物通过抑制 P-LAP 增加了内源性 AVP 水平，从而减少了尿量。因此，本发明提供的化合物有望用作基于 P-LAP 抑制作用的夜尿症治疗剂。
• PYRIDINE DERIVATIVE
  申请人：ASTELLAS PHARMA INC.

  公开号：US20170190715A1

  公开（公告）日：2017-07-06

  The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-[4-(substituted pyridine)-2-yl]methyl}-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.