methyl (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-pyridin-2-ylamino)pyrrolidine-2-carboxylate | 401568-95-4

• 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: methyl (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-pyridin-2-ylamino)pyrrolidine-2-carboxylate
• 英文别名: methyl (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-2-pyridylamino)pyrrolidine-2-carboxylate；1-O-tert-butyl 2-O-methyl (2S,4R)-4-[(5-cyanopyridin-2-yl)amino]pyrrolidine-1,2-dicarboxylate
• CAS: 401568-95-4
• 化学式: C₁₇H₂₂N₄O₄
• 分子量: 346.386
• InChiKey: PRUSRVNSOMYPPG-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-pyridin-2-ylamino)pyrrolidine-2-carboxylate 在 sodium hydroxide 作用下， 生成 (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-pyridin-2-yl)aminopyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  1-((S)-γ-Substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of highly potent DPP-IV inhibitors

  摘要：

  1-(gamma-Substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for their inhibitory activity. In structure-activity relationship study at the gamma-position of proline, it became clear that compounds bearing (S)-stereochemistry were 20-fold more potent than the antipode. Of these compounds, the (3,4-dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showed the highest inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.077
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸甲酯 在 Pd-BaSO₄ sodium azide 、 氢气 、 三乙胺 作用下， 生成 methyl (2S,4R)-1-tert-butoxycarbonyl-4-(5-cyano-pyridin-2-ylamino)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  1-((S)-γ-Substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of highly potent DPP-IV inhibitors

  摘要：

  1-(gamma-Substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for their inhibitory activity. In structure-activity relationship study at the gamma-position of proline, it became clear that compounds bearing (S)-stereochemistry were 20-fold more potent than the antipode. Of these compounds, the (3,4-dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showed the highest inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.077

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。
• 1-((S)-γ-Substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of highly potent DPP-IV inhibitors
  作者：Hiroshi Sakashita、Hiroshi Kitajima、Mitsuharu Nakamura、Fumihiko Akahoshi、Yoshiharu Hayashi

  DOI：10.1016/j.bmcl.2005.03.077

  日期：2005.5

  1-(gamma-Substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for their inhibitory activity. In structure-activity relationship study at the gamma-position of proline, it became clear that compounds bearing (S)-stereochemistry were 20-fold more potent than the antipode. Of these compounds, the (3,4-dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showed the highest inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.