3-((S)-1-benzyloxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl)thiazolidine | 401566-46-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-((S)-1-benzyloxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl)thiazolidine
• 英文别名: benzyl (2S)-4-oxo-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate
• CAS: 401566-46-9
• 化学式: C₁₆H₁₈N₂O₄S
• 分子量: 334.396
• InChiKey: SUFVKUVKGDUALL-AWEZNQCLSA-N

物化性质

• 沸点：
  577.1±50.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  92.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-((S)-1-benzyloxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl)thiazolidine 在 氢溴酸 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 3-{(2S,4S)-4-[4-(5-chlorobenzimidazol-2-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine trihydrobromide
  参考文献：
  名称：

  Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group

  摘要：

  Hypoglycemic agents with a mechanism of depeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the gamma-position of the proline structure in the investigation of L-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-pi interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.033
• 作为产物：
  描述：

  benzyl (2S)-4-hydroxy-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate 在 三氧化硫吡啶 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 3-((S)-1-benzyloxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl)thiazolidine
  参考文献：
  名称：

  Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group

  摘要：

  Hypoglycemic agents with a mechanism of depeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the gamma-position of the proline structure in the investigation of L-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-pi interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.033

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。
• PROCESS FOR THE PREPARATION OF TENELIGLIPTIN
  申请人：GLENMARK PHARMACEUTICALS LIMITED; GLENMARK GENERICS LIMITED

  公开号：US20150203484A1

  公开（公告）日：2015-07-23

  A process for the preparation of teneligliptin.

  一种制备替格列奈的方法。
• 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