tert-butyl (2S,4S)-4-[4-(2-methylquinolin-4-yl)piperazin-1-yl]-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate | 401567-56-4

• 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-(2-methylquinolin-4-yl)piperazin-1-yl]-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate
• CAS: 401567-56-4
• 化学式: C₂₇H₃₇N₅O₃S
• 分子量: 511.688
• InChiKey: MTXQMZOKIQZIIP-RDPSFJRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  94.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4S)-4-[4-(2-methylquinolin-4-yl)piperazin-1-yl]-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 120.0h， 生成 3-{(2S,4S)-4-[4-(2-methylquinolin-4-yl)piperazin-1-yl]-pyrrolidin-2-ylcarbonyl}thiazolidine trihydrochloride
  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：

  (2S,4R)-4-羟基-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯 在 三氧化硫吡啶 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 tert-butyl (2S,4S)-4-[4-(2-methylquinolin-4-yl)piperazin-1-yl]-2-(1,3-thiazolidine-3-carbonyl)pyrrolidine-1-carboxylate
  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。
• 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