3-[(2S,4S)-4-benzylamino-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl]-1,3-thiazolidine | 401565-04-6

• 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)-4-benzylamino-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl]-1,3-thiazolidine
• 英文别名: tert-butyl (2S,4S)-4-(benzylamino)-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate
• CAS: 401565-04-6
• 化学式: C₂₀H₂₉N₃O₃S
• 分子量: 391.535
• InChiKey: SCZUPEQOPZYOIT-IRXDYDNUSA-N

物化性质

• 沸点：
  563.9±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(2S,4S)-4-benzylamino-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 以74%的产率得到3-((2S,4S)-4-benzylamino-2-pyrrolidinylcarbonyl)-1,3-thiazolidine dihydrochloride
  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：

  在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以742 mg的产率得到3-[(2S,4S)-4-benzylamino-1-tert-butoxycarbonyl-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

• Proline derivatives and use thereof as drugs
  申请人：Kitajima Hiroshi

  公开号：US20050245538A1

  公开（公告）日：2005-11-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗效果的化合物，其作用是通过DPP-IV的抑制作用，并且作为药物产品具有令人满意的效果。本发明人发现，在丙氨酸的γ位上引入取代基的衍生物具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• Proline derivatives and the use thereof as drugs
  申请人：——

  公开号：US20040106655A1

  公开（公告）日：2004-06-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the &ggr;-position of proline represented by the formula (I) 1 wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗作用的化合物，由于DPP-IV抑制作用而具有满意的药物产品。本发明人发现，具有引入取代基的脯氨酸γ-位置的衍生物，其化学式为(I)1，其中每个符号如规范中所定义，具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP1308439B1

  公开（公告）日：2008-10-15
• US7060722B2
  申请人：——

  公开号：US7060722B2

  公开（公告）日：2006-06-13
• US7074794B2
  申请人：——

  公开号：US7074794B2

  公开（公告）日：2006-07-11