(S)-1-((S)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid amide | 64774-32-9

• 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: (S)-1-((S)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid amide
• 英文别名: L-phenylalanyl-L-prolinamide；(2S)-1-[(2S)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carboxamide
• CAS: 64774-32-9
• 化学式: C₁₄H₁₉N₃O₂
• 分子量: 261.324
• InChiKey: HAZDSEVQCDGJTA-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  89.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-cinnamoylglycine 、 (S)-1-((S)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid amide 生成 cinnamoyl(E)-Gly-Phe-Pro-NH2
  参考文献：
  名称：

  FIEZ-VANDAL, PIERRE-YVES

  摘要：

  DOI：
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 N-羟基琥珀酰亚胺酯 在 氢溴酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (S)-1-((S)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid amide
  参考文献：
  名称：

  Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors

  摘要：

  The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + GlyTrp-Met-Asp-Phe-NH(2). Starting from Val-Pro-NHBu, a dipeptide of submicromolar affinity that had previously been generated to serve as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18, K(i) = 80 nM). Further transformation (by making a benzologue) gave the indoline analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity (Ki = 7 nM). Retrospective analysis suggested the possibility of a general approach to designing exopeptidase inhibitors starting from the structure of the first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe-NHBu (37), but this only had K(i) = 9.4 mu M. Molecular modeling, to determine the minimum energy conformations and explain the 1000-fold better affinity of butabindide, indicated that 37 cannot access the likely active conformation of butabindide.

  DOI：

  10.1021/jm0500830

文献信息

• Histidyl peptide derivatives
  申请人：Japan Tobacco Inc.

  公开号：US05151497A1

  公开（公告）日：1992-09-29

  Novel peptide derivatives of the following formula ##STR1## wherein each symbol is as defined in the specification, pharmaceutically acceptable acid addition salts thereof and analogous copounds thereof. Since the derivatives and their pharmaceutically acceptable acid addition salts of the present invention possess stronger actions on central nervous system (e.g. antagonistic action against hypothermia, locomotor stimulant action, signal reflex stimulant action), they are of use as a therapeutic medicament for central nervous disorders such as impaired consciousness, depression, hypomnesia, the like in association association with schizophrenia, melancholia, senile dementia, sequelae of cerebrovascular disorders, head trauma, epilepsy and spinocerebellar degeneracy.

  以下是该句子的中文翻译： 新型的肽衍生物符号如规范中所定义的以下公式： ##STR1## 其中每个符号如规范所定义，其药物可接受的酸盐衍生物和类似化合物。由于本发明的衍生物及其药物可接受的酸盐具有更强的中枢神经系统作用（例如对抗低体温、运动刺激作用、信号反射刺激作用），因此它们可用作治疗中枢神经系统障碍的药物，例如与精神分裂症、忧郁症、老年性痴呆、脑血管疾病后遗症、头部外伤、癫痫和脊髓小脑变性相关的意识障碍、记忆障碍等。
• Tripeptides and tripeptide derivatives for the treatment of postlesional diseases of the nervous system
  申请人：Rapin Jean

  公开号：US20050080016A1

  公开（公告）日：2005-04-14

  The invention relates to the use of specific tripeptides for the treatment of postlesional diseases of ischemic, traumatic or toxic origin. The tripeptide derivatives satisfy the following formula (I): (see formula I as in paper form) wherein X represents OH, (C 1-5 ) alkoxy, NH 2 , NH—C 1-5 -alkyl, N(C 1-5 alkyl) 2 ; R 1 is a residue derived from one of the amino acids Phe, Tyr, Trp, Pro, which each may be optionally substituted with one or more (C 1-5 ) alkoxy groups, (C 1-5 ) alkyl groups or halogen atoms, as well as Ala, Val, Leu or Ile; R 2 is a residue derived from one of the amino acids Gly, Ala, Ile, Val, Ser, Thr, and Pro; Y 1 and Y 2 independently from each other represent H or (C 1-5 ) alkyl; R 3 and R 4 independently from each other represent H, OH, (C 1-5 ) alkyl or (C 1-5 ) alkoxy, provided that R 3 and R 4 are not both OH or (C 1-5 ) alkoxy; and R 5 represents H, OH, (C 1-5 ) alkyl or (C 1-5 ) alkoxy; or a pharmaceutically acceptable salt thereof.

  本发明涉及使用特定三肽治疗缺血性、创伤性或毒性后损伤性疾病。该三肽衍生物满足以下式子（I）：（见论文中的式子I） 其中，X代表OH、（C1-5）烷氧基、NH2、NH-C1-5-烷基、N（C1-5烷基）2；R1是来自苯丙氨酸、酪氨酸、色氨酸、脯氨酸中的一种氨基酸残基，每个氨基酸残基都可以选择性地用一个或多个（C1-5）烷氧基、（C1-5）烷基或卤原子取代，以及丙氨酸、缬氨酸、亮氨酸或异亮氨酸；R2是来自甘氨酸、丙氨酸、异亮氨酸、缬氨酸、丝氨酸、苏氨酸和脯氨酸中的一种氨基酸残基；Y1和Y2分别表示H或（C1-5）烷基；R3和R4分别表示H、OH、（C1-5）烷基或（C1-5）烷氧基，前提是R3和R4不同时为OH或（C1-5）烷氧基；R5表示H、OH、（C1-5）烷基或（C1-5）烷氧基；或其药学上可接受的盐。
• Tripeptides and tripeptide derivatives for the treatment of neurodegenerative diseases
  申请人：Rapin Jean

  公开号：US20050101538A1

  公开（公告）日：2005-05-12

  The invention relates to the use of specific tripeptides for the treatment of neurodegenerative diseases, and to pharmaceutical compositions comprising the tripeptides. The tripeptide derivatives satisfy the following formula (I): wherein X represents OH, (C 1-5 ) alkoxy, NH 2 , NH—C 1-5 -alkyl, N(C 1-5 alkyl) 2 ; R 1 is a residue derived from one of the amino acids Phe, Tyr, Trp, Pro, which each may be optionally substituted with one or more (C 1-5 )alkoxy groups, (C 1-5 )alkyl groups or halogen atoms, as well as Ala, Val, Leu or Ile; R 2 is a residue derived from one of the amino acids Gly, Ala, Ile, Val, Ser, Thr, Leu and Pro; Y 1 and Y 2 independently from each other represent H or (C 1-5 )alkyl; R 3 and R 4 independently from each other represent H, OH, (C 1-5 )alkyl or (C 1-5 )alkoxy, provided that R 3 and R 4 are not both OH or (C 1-5 )alkoxy; and R 5 represents H, OH, (C 1-5 )alkyl or (C 1-5 )alkoxy; or a pharmaceutically acceptable salt thereof.

  本发明涉及使用特定三肽治疗神经退行性疾病，以及包含该三肽的药物组合物。该三肽衍生物满足以下公式（I）：其中X代表OH，（C1-5）烷氧基，NH2，NH-（C1-5）烷基，N（C1-5烷基）2；R1是从苯丙氨酸，酪氨酸，色氨酸，脯氨酸中的一个衍生的残基，每个残基可选择地用一个或多个（C1-5）烷氧基，（C1-5）烷基或卤素原子取代，以及丙氨酸，缬氨酸，亮氨酸或异亮氨酸；R2是从甘氨酸，丙氨酸，异亮氨酸，缬氨酸，丝氨酸，苏氨酸，亮氨酸和脯氨酸中的一个衍生的残基；Y1和Y2各自独立地表示H或（C1-5）烷基；R3和R4各自独立地表示H，OH，（C1-5）烷基或（C1-5）烷氧基，前提是R3和R4不是OH或（C1-5）烷氧基；R5表示H，OH，（C1-5）烷基或（C1-5）烷氧基；或其药学上可接受的盐。
• Tripeptides and tripeptide derivatives for the treatment of postlesional disease of the nervous system
  申请人：Neurotell AG

  公开号：US07122524B2

  公开（公告）日：2006-10-17

  The invention relates to the use of specific tripeptides for the treatment of postlesional diseases of ischemic, traumatic or toxic origin. The tripeptide derivatives satisfy the following formula (I): (see formula I as in paper form) wherein X represents OH, (C1-5) alkoxy, NH2, NH—C1-5-alkyl, N(C1-5 alkyl)2; R1 is a residue derived from one of the amino acids Phe, Tyr, Trp, Pro, which each may be optionally substituted with one or more (C1-5) alkoxy groups, (C1-5) alkyl groups or halogen atoms, as well as Ala, Val, Leu or Ile; R2 is a residue derived from one of the amino acids Gly, Ala, Ile, Val, Ser, Thr, and Pro; Y1 and Y2 independently from each other represent H or (C1-5) alkyl; R3 and R4 independently from each other represent H, OH, (C1-5) alkyl or (C1-5) alkoxy, provided that R3 and R4 are not both OH or (C1-5) alkoxy; and R5 represents H, OH, (C1-5) alkyl or (C1-5) alkoxy; or a pharmaceutically acceptable salt thereof.

  本发明涉及使用特定三肽治疗缺血、创伤或毒性起源的后损伤疾病。该三肽衍生物满足以下公式（I）：（见纸质形式的公式I），其中X代表OH，（C1-5）烷氧基，NH2，NH-C1-5-烷基，N（C1-5烷基）2；R1是来自苯丙氨酸、酪氨酸、色氨酸、脯氨酸中的一种氨基酸残基，每种氨基酸残基可选择地被一个或多个（C1-5）烷氧基、（C1-5）烷基或卤原子取代，以及丙氨酸、缬氨酸、亮氨酸或异亮氨酸；R2是来自甘氨酸、丙氨酸、异亮氨酸、缬氨酸、丝氨酸、苏氨酸和脯氨酸中的一种氨基酸残基；Y1和Y2独立地表示H或（C1-5）烷基；R3和R4独立地表示H、OH、（C1-5）烷基或（C1-5）烷氧基，前提是R3和R4不同时为OH或（C1-5）烷氧基；而R5表示H、OH、（C1-5）烷基或（C1-5）烷氧基；或其药学上可接受的盐。
• Tandem Electrochemical Oxidative Azidation/Heterocyclization of Tryptophan‐Containing Peptides under Buffer Conditions
  作者：Yiyi Weng、Xiaobin Xu、Hantao Chen、Yiyang Zhang、Xianfeng Zhuo

  DOI：10.1002/anie.202206308

  日期：2022.10.10

  Manganese-catalyzed late-stage derivatization was used to construct azide-substituted tetrazolo[1,5-a]indole-containing peptides through a radical azidation/heterocyclization cascade. This electrochemical oxidative strategy could be conducted under mild, efficient, and environmentally friendly conditions in buffer solution.

  锰催化后期衍生化用于通过自由基叠氮化/杂环化级联构建叠氮取代的四唑并[1,5- a ]吲哚肽。这种电化学氧化策略可以在缓冲溶液中温和、高效、环保的条件下进行。