N-(N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-prolyl)-2(S)-(acetoxyacetyl)pyrrolidine | 725265-94-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-(N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-prolyl)-2(S)-(acetoxyacetyl)pyrrolidine
• 英文别名: 4-phenylbutanoyl-5(R)-tert-butyl-L-prolyl-2(S)-(acetoxyacetyl)-pyrrolidine；[2-[(2S)-1-[(2S,5R)-5-tert-butyl-1-(4-phenylbutanoyl)pyrrolidine-2-carbonyl]pyrrolidin-2-yl]-2-oxoethyl] acetate
• CAS: 725265-94-1
• 化学式: C₂₇H₃₈N₂O₅
• 分子量: 470.609
• InChiKey: FTWUCEYLJJBVQO-WPFOTENUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-prolyl)-2(S)-(acetoxyacetyl)pyrrolidine 在 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以95%的产率得到KYP-2117
  参考文献：
  名称：

  Conformationally rigid N-acyl-5-alkyl-l-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In the N-acyl-(L)-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-(L)-prolyl groups, resulting in a series of N-acyl-5-alkyl-(L)-prolyl-pyrrolidines. Since N-amides of 5-alkyl-(L)-prolines are conformationally more rigid than those of (L)-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00363-8
• 作为产物：
  描述：

  4-苯基丁酰氯 在 lithium hydroxide 、 三甲基乙酰氯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 N-(N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-prolyl)-2(S)-(acetoxyacetyl)pyrrolidine
  参考文献：
  名称：

  Conformationally rigid N-acyl-5-alkyl-l-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In the N-acyl-(L)-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-(L)-prolyl groups, resulting in a series of N-acyl-5-alkyl-(L)-prolyl-pyrrolidines. Since N-amides of 5-alkyl-(L)-prolines are conformationally more rigid than those of (L)-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00363-8

文献信息

• Compounds having prolyl oligopeptidase inhibitory activity
  申请人：Gynther Jukka

  公开号：US20060229254A1

  公开（公告）日：2006-10-12

  A compound of formula (I), wherein X, R 1 , R 2 and R 3 are as defined in the disclosure, or a pharmaceutically acceptable salt or ester thereof, useful as a prolyl oligopeptidase inhibitor. The compounds can be used for the treatment of diseases or conditions where prolyl oligopeptidase inhibitors are indicated to be effective, for example for the treatment of neurodegenerative diseases, such as Alzheimer's disease and senile dementia.

  式(I)的化合物，其中X、R1、R2和R3如所披露的定义，或其药学上可接受的盐或酯，可用作脯氨酰寡肽酶抑制剂。这些化合物可用于治疗需要脯氨酰寡肽酶抑制剂具有疗效的疾病或情况，例如用于治疗神经退行性疾病，如阿尔茨海默病和老年性痴呆症。
• COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY
  申请人：Orion Corporation

  公开号：EP1581489A2

  公开（公告）日：2005-10-05
• [EN] COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY<br/>[FR] COMPOSES PRESENTANT UN EFFET INHIBITEUR SUR LA PROLYL-OLIGOPEPTIDASE
  申请人：ORION CORP

  公开号：WO2004060862A2

  公开（公告）日：2004-07-22

  The invention provides a compound of formula (I), wherein in the formula X, R1, R2 and R3 are as defined in claim 1, or a pharmaceutically acceptable salt or ester thereof, useful as a prolyl oligopeptidase inhibitor. The compounds of formula (I) can be used for the treatment of diseases or conditions where prolyl oligopeptidase inhibitors are indicated to be effective, for example for the treatment of neurodegenerative diseases, such as Alzheimer's disease and senile dementia