ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(3R,4S)-isopropylidenedioxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate | 317354-96-4

• 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 [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(3R,4S)-isopropylidenedioxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate
• CAS: 317354-96-4
• 化学式: C₃₃H₄₃N₅O₈
• 分子量: 637.733
• InChiKey: DKDUKPWGXCTDNZ-NSGJQZOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  46.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  138.98
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(3R,4S)-isopropylidenedioxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 以37%的产率得到2-(4-{[(3aR,4S,6aS)-5-[2-(3-methoxy-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]-2,2-dimethyl-hexahydro-[1,3]dioxolo[4,5-c]pyrrol-4-yl]carbonyl}piperazin-1-yl)acetic acid
  参考文献：
  名称：

  Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

  摘要：

  A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12ml/min/kg and 11p 9ml/min/kg). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.058
• 作为产物：
  描述：

  methyl 1-benzyloxycarbonyl-(4S)-phenylseleno-(2S)-pyrrolidinylcarboxylate 在 palladium on activated charcoal 、 四氧化锇 吡啶 、 sodium hydroxide 、 水 、 氢气 、 双氧水 、 1-羟基苯并三唑 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 83.0h， 生成 ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(3R,4S)-isopropylidenedioxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate
  参考文献：
  名称：

  Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

  摘要：

  A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12ml/min/kg and 11p 9ml/min/kg). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.058