L-prolyl-pyrrolidine hydrochloride | 137998-15-3

• 英文名称: L-prolyl-pyrrolidine hydrochloride
• 英文别名: L-prolyl-pyrrolidin-hydrochloric acid salt；pyrrolidin-1-yl-[(2S)-pyrrolidin-2-yl]methanone;hydrochloride
• CAS: 137998-15-3
• 化学式: C₉H₁₆N₂O*ClH
• 分子量: 204.7
• InChiKey: NFNGYUXIXLYXKH-QRPNPIFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.78
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  L-prolyl-pyrrolidine hydrochloride 在 lithium hydroxide 、 三甲基乙酰氯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 isophthalic acid L-proline L-prolyl-pyrrolidine amide
  参考文献：
  名称：

  New Prolyl Oligopeptidase Inhibitors Developed from Dicarboxylic Acid Bis(l-prolyl-pyrrolidine) Amides

  摘要：

  Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl. group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)(hydroxyacetyl)pyrrolidinyl groups.

  DOI：

  10.1021/jm030811o
• 作为产物：
  描述：

  tert-butyl (S)-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 L-prolyl-pyrrolidine hydrochloride
  参考文献：
  名称：

  α-氨基酰胺作为戈德堡酰胺化反应的配体

  摘要：

  已显示α-氨基酰胺可用作戈德堡酰胺化中的配体。检查了许多α-氨基酰胺，并探讨了在α-氨基酰胺上取代的重要性。乙酰胺由于其低成本，稳定性和方便性而作为保护基团而成为亲核偶联伴侣。探索了这些催化剂的初始底物范围，包括电子活化和失活的芳基溴化物，但是o-取代的芳基溴化物是有问题的。

  DOI：

  10.1016/j.tetlet.2013.09.099

文献信息

• Synthesis of Prolyl Endopeptidase Inhibitors and Evaluation of Their Structure-Activity Relationships: In Vitro Inhibition of Prolyl Endopeptidase from Canine Brain.
  作者：Heihachiro ARAI、Hiroyasu NISHIOKA、Seiichi NIWA、Takeshi YAMANAKA、Yoshiaki TANAKA、Koji YOSHINAGA、Naomi KOBAYASHI、Naoyoshi MIURA、Yugo IKEDA

  DOI：10.1248/cpb.41.1583

  日期：——

  By chemical modification of a known prolyl endopeptidase (PEP) inhibitor (N-[N-(4-phenylbutanoyl)-L-prolyl]pyrrolidine; SUAM-1221), several arylalkanoyl derivatives (V-1-27) were synthesized and tested for in vitro inhibitory activity towards PEP from canine brain. Among them, 4-(2-thienyl)butanoyl derivatives (V-24-27) showed more potent PEP-inhibitory activity than SUAM-1221. The structure-activity relationships of these compounds are discussed.

  通过对一种已知的脯氨酰内肽酶（PEP）抑制剂（N-[N-（4-苯基丁酰基）-L-脯氨酰]吡咯烷；SUAM-1221）进行化学修饰，合成了几种芳基烷酰基衍生物（V-1-27），并测试了其对犬脑中 PEP 的体外抑制活性。其中，4-（2-噻吩基）丁酰衍生物（V-24-27）显示出比 SUAM-1221 更强的 PEP 抑制活性。本文讨论了这些化合物的结构-活性关系。
• 一种双手性联萘O-N-N三齿配体及其制备方法
  申请人：南开大学

  公开号：CN113416162B

  公开（公告）日：2023-02-10

  一种双手性联萘O‑N‑N三齿配体及其制备方法。所述配体具有式(L)所示结构式。其制备包括以下步骤：(1)以手性2‑甲基‑2‑甲氧基‑联萘为原料，经芳香环取代反应、羟基保护基替代、溴代反应得到联萘溴化衍生物(化合物IV)；(2)从保护的手性脯氨酸出发，经过转化获得各种二胺结构(化合物B)；(3)化合物IV和化合物B在碱性条件、催化剂存在下偶联，再脱去保护基得到具有双手性的联萘O‑N‑N三齿配体L。该类配体具有中心手性和轴手性，同时表现出路易斯碱性和布朗斯特酸性，具备出色的空间结构和电子性质，能够在不对称催化反应中表现出优秀的性能。该类配体制备方法简单原料易得，对不对称有机合成具有重要意义。
• [EN] COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY, METHODS FOR THEIR PREPARATION AND THEIR USE<br/>[FR] COMPOSES INHIBITEURS DE LA PROLYL OLIGOPEPTIDASE, PROCEDES DE PREPARATION ET UTILISATION
  申请人：ORION CORP

  公开号：WO2003004468A1

  公开（公告）日：2003-01-16

  Compounds of the formula (I), wherein the symbol aa means a residue of an α-amino acid. The invention is also directed to a method for the preparation of the compounds of formula (I), as well as their use as prolyl oligopeptide inhibitors, for example for the treatment of Alzheimer's disease.

  公式（I）的化合物，其中符号aa表示α-氨基酸的残基。本发明还涉及一种制备公式（I）化合物的方法，以及它们作为脯氨酰寡肽抑制剂的用途，例如用于治疗阿尔茨海默病。
• Compounds having prolyl oligopeptidase inhibitory activity, methods for their preparation and their use
  申请人：Gynther Jukka

  公开号：US20050020677A1

  公开（公告）日：2005-01-27

  Compounds of the formula (I), wherein the symbol aa means a residue of an α-amino acid. The invention is also directed to a method for the preparation of the compounds of formula (I), as well as their use as prolyl oligopeptide inhibitors, for example for the treatment of Alzheimer's disease.

  式(I)的化合物，其中符号aa表示α-氨基酸残基。本发明还涉及一种制备式(I)化合物的方法，以及它们作为脯氨酰寡肽酶抑制剂的用途，例如用于治疗阿尔茨海默病。
• Prolylendopeptidase inhibitors
  申请人：Chinoin Gyogyszer es Vegyeszeti

  公开号：US06191161B1

  公开（公告）日：2001-02-20

  The present invention relates to new prolylendopeptidase inhibitors of general formula (I).

  本发明涉及一种新的普罗林内肽酶抑制剂，其化学式为(I)。