tert-butyl (2S,4S)-4-({4-[3-(methoxymethyl)-1,2,4-thiadiazol-5-yl]-1-piperazinyl}carbonyl)-2-(1-pyrrolidinylcarbonyl)-1-pyrrolidinecarboxylate | 1019638-01-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl (2S,4S)-4-({4-[3-(methoxymethyl)-1,2,4-thiadiazol-5-yl]-1-piperazinyl}carbonyl)-2-(1-pyrrolidinylcarbonyl)-1-pyrrolidinecarboxylate
• CAS: 1019638-01-7
• 化学式: C₂₃H₃₆N₆O₅S
• 分子量: 508.642
• InChiKey: RJBFUKMOBFXNSY-IRXDYDNUSA-N

物化性质

• 沸点：
  697.4±65.0 °C(predicted)
• 密度：
  1.306±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  108.41
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4S)-4-({4-[3-(methoxymethyl)-1,2,4-thiadiazol-5-yl]-1-piperazinyl}carbonyl)-2-(1-pyrrolidinylcarbonyl)-1-pyrrolidinecarboxylate 在 盐酸 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 16.0h， 以75%的产率得到1-[3-(methoxymethyl)-1,2,4-thiadiazol-5-yl]-4-{[(3S,5S)-5-(1-pyrrolidinylcarbonyl)-3-pyrrolidinyl]carbonyl}-1,4-diazepane monohydrochloride
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031
• 作为产物：
  描述：

  (3S,5S)-1-(tert-butoxycarbonyl)-5-(1-pyrrolidinylcarbonyl)-3-pyrrolidinecarboxylic acid 、 3-(Methoxymethyl)-5-piperazin-1-yl-1,2,4-thiadiazole 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 tert-butyl (2S,4S)-4-({4-[3-(methoxymethyl)-1,2,4-thiadiazol-5-yl]-1-piperazinyl}carbonyl)-2-(1-pyrrolidinylcarbonyl)-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031