ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-phenoxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate | 886447-49-0

• 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 [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-phenoxy-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate
• CAS: 886447-49-0
• 化学式: C₃₆H₄₃N₅O₇
• 分子量: 657.767
• InChiKey: ANHHSZJJDFAPKR-IZEXYCQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  48.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  129.75
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-phenoxy-(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100%的产率得到2-(4-{[(2S,4S)-1-[2-(3-methoxy-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]-4-phenoxypyrrolidin-2-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-tert-butoxycarbonyl)-(4S)-phenoxy-(2S)-pyrrolidinylcarboxylate 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 ethyl [4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-phenoxy-(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