1-[(2S)-氨基-1-氧代-3-苯基丙基]吡咯烷单(三氟乙酸盐) | 144646-34-4

• 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
• 中文名称: 1-[(2S)-氨基-1-氧代-3-苯基丙基]吡咯烷单(三氟乙酸盐)
• 英文名称: 1-(L-phenylalanyl)pyrrolidine trifluoroacetate
• 英文别名: 1-[(2S)-Amino-1-oxo-3-phenylpropyl]pyrrolidine mono(trifluoroacetate)；(2S)-2-amino-3-phenyl-1-pyrrolidin-1-ylpropan-1-one;2,2,2-trifluoroacetic acid
• CAS: 144646-34-4
• 化学式: C₂HF₃O₂*C₁₃H₁₈N₂O
• 分子量: 332.323
• InChiKey: JECDIUYILCAULH-YDALLXLXSA-N

物化性质

• 溶解度：
  甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.81
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[(2S)-氨基-1-氧代-3-苯基丙基]吡咯烷单(三氟乙酸盐) 、 间苯二甲酰氯 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 isophthalic acid bis(L-phenylalanyl-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：

  BOC-L-苯丙氨酸琥珀酰亚胺酯 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-[(2S)-氨基-1-氧代-3-苯基丙基]吡咯烷单(三氟乙酸盐)
  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

文献信息

• A New General Approach to Enantiomerically Pure Cyclic and Open-Chain (<i>R</i>)- and (<i>S</i>)-α,α-Disubstituted α-Amino Acids
  作者：Daniel Obrecht、Clive Spiegler、Peter Schönholzer、Klaus Müller、Heinz Heimgartner、Friedrich Stierli

  DOI：10.1002/hlca.19920750522

  日期：1992.8.13

  racemic N-acylated α,α-disubstituted amino acids were resolved by coupling to chiral amines 15-18 derived from (S)-phenylalanine to form diastereoisomers 19/20 or 21/22 that could be separated by crystallization and/or flash chromatography on silica gel (Scheme 3). Selective cleavage via the 1,3-oxazol-5(4H)-ones 10a-p gave the corresponding optically pure α,α-disubstituted amino-acid derivatives 11 or

  制备了各种各样的环状和开链α，α-二取代的α-氨基酸1a-p。通过与衍生自（S）-苯丙氨酸的手性胺15-18偶联，拆分外消旋N-酰化的α，α-二取代氨基酸，形成非对映异构体19/20或21/22，可以通过结晶和/或快速色谱分离在硅胶上（方案3）。通过1,3-恶唑-5（4 H）-酮10a-p的选择性裂解以高收率得到相应的光学纯α，α-二取代氨基酸衍生物11或12（方案3）。α，α-二取代氨基酸的绝对构型由非对映异构体20、21g'，22d的X射线结构确定。
• [EN] DIPEPTIDYL PEPTIDASE INHIBITORS<br/>[FR] INHIBITEURS DE DIPEPTIDYLE PEPTIDASE
  申请人：AIC

  公开号：WO2004076433A1

  公开（公告）日：2004-09-10

  The present invention relates to novel inhibitors of serine type peptidases in general and of serine type dipeptidyl peptidases in particular. The present invention further relates to the use of the dipeptidyl peptidase inhibitors for selective inhibition of dipeptidyl peptidases. The present invention also relates to pharmaceutical compositions comprising these novel dipeptidyl peptidase inhibitors. The present invention further relates to the use of the novel inhibitors in therapy, diagnosis and research.

  本发明涉及一般性的新型丝氨酸型肽酶抑制剂，特别是丝氨酸型二肽基肽酶的抑制剂。本发明还涉及利用二肽基肽酶抑制剂对二肽基肽酶进行选择性抑制。本发明还涉及包含这些新型二肽基肽酶抑制剂的药物组合物。本发明还涉及在治疗、诊断和研究中使用这些新型抑制剂。
• [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。
• Design, Synthesis, and SAR of Potent and Selective Dipeptide-Derived Inhibitors for Dipeptidyl Peptidases
  作者：Kristel Senten、Pieter Van der Veken、Ingrid De Meester、Anne-Marie Lambeir、Simon Scharpé、Achiel Haemers、Koen Augustyns

  DOI：10.1021/jm0308803

  日期：2003.11.1

  In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P-1 and P-2 building blocks led to the discovery of some very potent DPP II inhibitors which can be characterized by their high selectivity for DPP II with regard to DPP IV. Dab-Pip and Dab-Pip-2-CN were selected as the most promising inhibitors (IC50 nM range) and will enable us to study the physiological role of DPP II and to differentiate between DPP 11 and DPP IV in biological systems.