3-[(2S,4S)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-pyrrolidinylcarbonyl]-1,3-thiazolidine | 401564-35-0

• 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: 3-[(2S,4S)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-pyrrolidinylcarbonyl]-1,3-thiazolidine
• 英文别名: 3-[(2S,4S)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)pyrrolidinylcarbonyl]thiazolidine；tert-butyl (2S,4S)-4-[tert-butyl(dimethyl)silyl]oxy-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate
• CAS: 401564-35-0
• 化学式: C₁₉H₃₆N₂O₄SSi
• 分子量: 416.657
• InChiKey: LJSKNLWGRPCYNI-GJZGRUSLSA-N

物化性质

• 沸点：
  493.7±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  84.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(2S,4S)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 在 盐酸 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 3-[(2S,4S)-4-(4-cyanobenzoyl)oxy-2-pyrrolidinylcarbonyl]-1,3-thiazolidine
  参考文献：
  名称：

  Lead optimization of [(S)-γ-(arylamino)prolyl]thiazolidine focused on γ-substituent: Indoline compounds as potent DPP-IV inhibitors

  摘要：

  Dipeptidyl peptidase IV (DPP-IV) inhibitors are looked to as a potential new antidiabetic agent class. A series of [(S)-gamma-(arylamino)prolyl]thiazolidine compounds in which the electrophilic nitrile is removed are chemically stable DPP-IV inhibitors. To discover a structure for the gamma-substituent of the proline moiety more suitable for interacting with the S-2 pocket of DPP-IV, optimization focused on the gamma-substituent was carried out. The indoline compound 22e showed a DPP-IV-inhibitory activity 100-fold more potent than that of the prolylthiazolidine 10 and comparable to that of NVP-DPP728. It also displayed improved inhibitory selectivity for DPP-IV over DPP8 and DPP9 compared to compound 10. Indoline compounds such as 22e have a rigid conformation with double restriction of the aromatic moiety by proline and indoline structures to promote interaction with the binding site in the S2 pocket of DPP-IV. The double restriction effect provides a potent inhibitory activity which compensates for the decrease in activity caused by removing the electrophilic nitrile. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.059
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 咪唑 、 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 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 3-[(2S,4S)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-pyrrolidinylcarbonyl]-1,3-thiazolidine
  参考文献：
  名称：

  Lead optimization of [(S)-γ-(arylamino)prolyl]thiazolidine focused on γ-substituent: Indoline compounds as potent DPP-IV inhibitors

  摘要：

  Dipeptidyl peptidase IV (DPP-IV) inhibitors are looked to as a potential new antidiabetic agent class. A series of [(S)-gamma-(arylamino)prolyl]thiazolidine compounds in which the electrophilic nitrile is removed are chemically stable DPP-IV inhibitors. To discover a structure for the gamma-substituent of the proline moiety more suitable for interacting with the S-2 pocket of DPP-IV, optimization focused on the gamma-substituent was carried out. The indoline compound 22e showed a DPP-IV-inhibitory activity 100-fold more potent than that of the prolylthiazolidine 10 and comparable to that of NVP-DPP728. It also displayed improved inhibitory selectivity for DPP-IV over DPP8 and DPP9 compared to compound 10. Indoline compounds such as 22e have a rigid conformation with double restriction of the aromatic moiety by proline and indoline structures to promote interaction with the binding site in the S2 pocket of DPP-IV. The double restriction effect provides a potent inhibitory activity which compensates for the decrease in activity caused by removing the electrophilic nitrile. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.059

文献信息

• Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
  作者：Tomohiro Yoshida、Fumihiko Akahoshi、Hiroshi Sakashita、Hiroshi Kitajima、Mitsuharu Nakamura、Shuji Sonda、Masahiro Takeuchi、Yoshihito Tanaka、Naoko Ueda、Sumie Sekiguchi、Takayuki Ishige、Kyoko Shima、Mika Nabeno、Yuji Abe、Jun Anabuki、Aki Soejima、Kumiko Yoshida、Yoko Takashina、Shinichi Ishii、Satoko Kiuchi、Sayaka Fukuda、Reiko Tsutsumiuchi、Keigo Kosaka、Takahiro Murozono、Yoshinobu Nakamaru、Hiroyuki Utsumi、Naoya Masutomi、Hiroyuki Kishida、Ikuko Miyaguchi、Yoshiharu Hayashi

  DOI：10.1016/j.bmc.2012.08.012

  日期：2012.10

  hypoglycemia. We explored linked bicyclic heteroarylpiperazines substituted at the γ-position of the proline structure in the course of the investigation of l-prolylthiazolidines. The efforts led to the discovery of a highly potent, selective, long-lasting and orally active DPP-4 inhibitor, 3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine (8g), which has

  二肽基肽酶IV（DPP-4）抑制是低血糖的低风险，因此是每日一次口服给药方案的合适机制。我们在研究1-脯氨酰咪唑烷的过程中，探索了在脯氨酸结构的γ位上取代的连接的双环杂芳基哌嗪。这些努力导致发现了一种高效，选择性，持久和口服活性的DPP-4抑制剂3-[（2 S，4 S）-4- [4-（3-甲基-1-苯基-1）H-吡唑-5-基）哌嗪-1-基]吡咯烷-2-基羰基]噻唑烷（8g），具有独特的结构，具有五个连续的环。X射线共晶体结构为8g在DPP-4中的研究表明，吡唑上的苯环和DPP-4的S 2广泛的亚位点之间的关键相互作用不仅提高了效力，而且还提高了选择性。0.03 mg / kg或更高剂量的化合物8g在口服Zucker脂肪大鼠体内后，显着抑制了血浆葡萄糖水平的增加。在日本，化合物8g（替利格列汀）已被批准用于治疗2型糖尿病。