N-(3-phenylpropionyl)-L-valine | 21957-67-5

• 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: N-(3-phenylpropionyl)-L-valine
• 英文别名: N-(3-phenylpropanoyl)-L-Val-OH；3-Phenyl-propionyl-L-valin；(S)-N-phenylethylcarbonylvaline；(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoic acid
• CAS: 21957-67-5
• 化学式: C₁₄H₁₉NO₃
• mdl: MFCD16377341
• 分子量: 249.31
• InChiKey: QCSHUNOZULVRRJ-ZDUSSCGKSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  479.4±38.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-phenylpropionyl)-L-valine 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 生成 5-Fluoro-3-[(S)-3-methyl-2-(3-phenyl-propionylamino)-butyrylamino]-4-oxo-pentanoic acid
  参考文献：
  名称：

  Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the N-protecting group

  摘要：

  This article describes the synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to contribute to caspase-3 inhibiting activity, and compounds with a large group such as Cbz are more active than compounds with a small group such as Ac. Compounds with more hydrophobic protecting groups were found to be more active in cell apoptosis protection assays, probably due to increased cell permeability. MX1122,2,4-di-Cl-Cbz-Val-Aspfmk, is identified as a potent broad-spectrum caspase inhibitor and is selective for caspases versus other proteases, with good activity in the cell apoptosis protection assays as well as good efficacy in the mouse liver apoptosis model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.027
• 作为产物：
  描述：

  L-缬氨酸甲酯盐酸盐 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-(3-phenylpropionyl)-L-valine
  参考文献：
  名称：

  Inhibition of Peptidylglycine .alpha.-Amidating Monooxygenase by N-Substituted Homocysteine Analogs

  摘要：

  C-terminal amidation is a posttranslational modification found in many neuropeptides. Peptidylglycine cl-amidating monooxygenase (PAM) catalyzes the synthesis of the biologically essential C-terminal amide from a glycine-extended precursor peptide. Reported herein are the first potent inhibitors of PAM. Dipeptides containing a C-terminal homocysteine and an N-acylated hydrophobic amino acid were found to inhibit PAM with IC(50)s in the low nanomolar range. Inhibition potency was dependent on both the carboxylate and the thiolate functionalities of the homocysteine and on the hydrophobic groups of the second amino acid. The thiolate was postulated to produce high binding affinities through coordination with the active-site copper. The compound series also exhibited potent inhibition of PAM in rat dorsal root ganglion cells as demonstrated by a dose-dependent increase in the substance P-Gly/substance P ratio. These results indicate that the compounds have sufficient potency and intracellular bioavailability to aid future studies focused on neuropeptide function and the contributions of neuropeptides to various disease processes.

  DOI：

  10.1021/jm00052a002

文献信息

• Convenient Peptide Synthesis without Protection of <i>C</i>-Terminals
  作者：Takuya Noguchi、Naoka Tehara、Yuki Uesugi、Seunghee Jung、Nobuyuki Imai

  DOI：10.1246/cl.2012.42

  日期：2012.1.5

  Condensation of carboxylic acids 1 and 5 with unprotected α-amino acids 2 via activation by ethyl chloroformate and triethylamine proceeded effectively to afford the corresponding amides in 50–99% yields. Tripeptide 7c was obtained in 42% yield from the dipeptide 6c in a similar manner.

  羧酸1和5与未保护的α-氨基酸2在乙基氯甲酸酯和三乙胺的活化下高效缩合，以50-99%的产率得到相应的酰胺。类似地，从二肽6c中以42%的产率获得了三肽7c。
• Methods of treating alzheimer's disease
  申请人：Schostarez Heinrich

  公开号：US20050130941A1

  公开（公告）日：2005-06-16

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of hydrazine compounds of formula (I) wherein the variables R 1 -R 9 are defined herein.

  本发明涉及使用式(I)中变量R1-R9所定义的肼化合物治疗阿尔茨海默病和其他疾病，抑制β-分泌酶酶活性，抑制A beta肽在哺乳动物体内的沉积。
• Peptide isosteres containing a heterocycle useful in the treatment of alzheimer's disease
  申请人：Varghese John

  公开号：US20050159460A1

  公开（公告）日：2005-07-21

  The present invention relates to methods of treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of known compounds of formula (I) wherein R 1 , R 2 , R 3 , U′, U″, V, Y, W, Q, R′ are as defined herein.

  本发明涉及使用式(I)中已知化合物的方法，其中R1、R2、R3、U'、U"、V、Y、W、Q、R'的定义如本文所述，用于治疗阿尔茨海默病和其他疾病，和/或抑制β-分泌酶酶，和/或抑制哺乳动物中Aβ肽的沉积。
• Retroviral protease inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0402646A1

  公开（公告）日：1990-12-19

  A retroviral protease inhibiting compound of the formula or a pharmaceutical acceptable salt, prodrug or ester thereof, wherein X is a linking group; A is (1) substituted amino, (2) substituted carbonyl, (3) functionalized imino, (4) functionalized alkyl, (5) functionalized acyl, (6) functionalized heterocyclic or (7) functionalized (heterocyclic)alkyl; and B is (1) substituted carbonyl independently defined as herein, (2) substituted amino independently defined as herein, (3) functionalized imino independently defined as herein, (4) functionalized alkyl independently defined as herein, (5) functionalized acyl independently defined as herein, (6) functionalized heterocyclic independently defined as herein or (7) functionalized (heterocyclic)alkyl independently defined as herein.

  式中的逆转录病毒蛋白酶抑制化合物 或其药物可接受的盐、原药或酯，其中 X 是连接基团； A 是 (1) 取代的氨基 (2) 取代的羰基 (3) 官能化亚氨基 (4) 官能化烷基 (5) 官能化酰基 (6) 官能化杂环或 (7) 官能化（杂环）烷基；且 B 是 (1) 如本文所独立定义的取代的羰基、 (2) 如本文所独立定义的取代氨基 (3) 如本文所独立定义的官能化亚氨基 (4) 如本文所独立定义的官能化烷基、 (5) 如本文所独立定义的官能化酰基、 (6) 如本文所独立定义的官能化杂环，或 (7) 本文独立定义的官能化（杂环）烷基。
• Antiretrovirale hydrazinderivate
  申请人：CIBA-GEIGY AG

  公开号：EP0604368A1

  公开（公告）日：1994-06-29

  Beschrieben werden Verbindungen der Formel worin R₁ und R₉ unabhängig voneinander Wasserstoff, Acyl, unsubstituiertes oder substituiertes Alkyl; Sulfo; oder durch unsubstituiertes oder substituiertes Alkyl, Aryl oder Heterocyclyl substituiertes Sulfonyl bedeuten, mit der Massgabe, dass höchstens einer der Reste R₁ und R₉ Wasserstoff bedeutet; und R₂ und R₈ jeweils unabhängig voneinander Wasserstoff oder unsubstituiertes oder substituiertes Alkyl bedeuten; R₃ und R₄ unabhängig voneinander Wasserstoff, unsubstituiertes oder substituiertes Alkyl, unsubstituiertes oder substituiertes Cycloalkyl oder Aryl bedeuten; R₅ Acyloxy bedeutet; R₆ Wasserstoff bedeutet; und R₇ unsubstituiertes oder substituiertes Alkyl, unsubstituiertes oder substituiertes Cycloalkyl oder Aryl bedeutet; sowie Salze der genannten Verbindungen, sofern salzbildende Gruppen vorliegen; diese Verbindungen zeigen antiretrovirale Wirksamkeit.

  式中的化合物 其中 R₁ 和 R𠢙 相互独立地为氢、酰基、未取代或取代的烷基；磺酰基；或被未取代或取代的烷基、芳基或杂环基取代的磺酰基，但 R₁ 和 R𠢙 自由基中最多有一个是氢；R₂ 和 R₈ 相互独立地为氢或未取代或取代的烷基； R₃ 和 R₄ 各自独立地为氢、未取代或取代的烷基、未取代或取代的环烷基或芳基； R₅ 表示酰氧基； R₆ 表示氢； R₇ 表示未取代或取代的烷基、未取代或取代的环烷基或芳基； 以及上述化合物的盐类，只要存在成盐基团；这些化合物具有抗逆转录病毒活性。