Leu-Val-Phe-OCH3*HCl | 73604-37-2

• 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: Leu-Val-Phe-OCH3*HCl
• 英文别名: L-leucyl-L-valyl-L-phenylalanine, methyl ester, hydrochloride；methyl (2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoate;hydrochloride
• CAS: 73604-37-2
• 化学式: C₂₁H₃₃N₃O₄*ClH
• 分子量: 427.972
• InChiKey: HBCZKTKSICRNED-UVJOBNTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Leu-Val-Phe-OCH3*HCl 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 氢气 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 Leu-Leu-Val-Phe-OMe hydrochloride
  参考文献：
  名称：

  Leu-Val-Phe-OCH3的N-（α-羟基烷酰基）衍生物作为肾素抑制剂。

  摘要：

  合成以下Leu-Val-Phe-OCH3的N-（α-羟基lakanoyl）衍生物并测试其抑制人羊膜肾素的能力：D-和L-α-羟基异己酰基-Leu-Val-Phe-OCH3，D-和L-α-羟基异戊基-Leu-Val-Phe-OCH3，L-2-羟基-3-苯基丙酰基-Leu-Val-Phe-OCH3以及D-和L-α-羟基苯基乙酰基-Leu-Val-Phe-OCH3 。通过使用Dixion图对化合物的分析显示，所有化合物都是肾素的竞争性抑制剂。发现除D-α-羟基异戊基-Leu-Val-Phe-OCH3以外的所有化合物都比已知的四肽抑制剂Leu-Leu-Val-Phe-OCH3更具活性（1）。该系列中两个活性最高的化合物是L-α-羟基异己酰基-Leu-Val-Phe-OCH3（Ki = 0.23 mM）和L-α-羟基异戊酰基-Leu-Val-Phe-OCH3（Ki = 0.3 mM）。

  DOI：

  10.1021/jm00180a017
• 作为产物：
  描述：

  Z-Leu-Val-Phe-OCH3 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 以89%的产率得到Leu-Val-Phe-OCH3*HCl
  参考文献：
  名称：

  Leu-Val-Phe-OCH3的N-（α-羟基烷酰基）衍生物作为肾素抑制剂。

  摘要：

  合成以下Leu-Val-Phe-OCH3的N-（α-羟基lakanoyl）衍生物并测试其抑制人羊膜肾素的能力：D-和L-α-羟基异己酰基-Leu-Val-Phe-OCH3，D-和L-α-羟基异戊基-Leu-Val-Phe-OCH3，L-2-羟基-3-苯基丙酰基-Leu-Val-Phe-OCH3以及D-和L-α-羟基苯基乙酰基-Leu-Val-Phe-OCH3 。通过使用Dixion图对化合物的分析显示，所有化合物都是肾素的竞争性抑制剂。发现除D-α-羟基异戊基-Leu-Val-Phe-OCH3以外的所有化合物都比已知的四肽抑制剂Leu-Leu-Val-Phe-OCH3更具活性（1）。该系列中两个活性最高的化合物是L-α-羟基异己酰基-Leu-Val-Phe-OCH3（Ki = 0.23 mM）和L-α-羟基异戊酰基-Leu-Val-Phe-OCH3（Ki = 0.3 mM）。

  DOI：

  10.1021/jm00180a017

文献信息

• Use of diamino alcohols as analgesic agents
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04670541A1

  公开（公告）日：1987-06-02

  An enkephalin-degrading aminopeptidase enzyme is inhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salt thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, alkyl, carboxyalkyl, halo substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl, or heteroaryl; R.sub.3 is hydroxy, alkoxy, (substituted alkyl)oxy, arylalkoxy, (heteroaryl)alkoxy or --NY.sub.1 Y.sub.2, wherein Y.sub.1 and Y.sub.2 are each independently hydrogen, alkyl, aryl, or arylalkyl or Y.sub.1 is hydrogen and Y.sub.2 is substituted alkyl or (heteroaryl)alkyl; A.sub.1 is glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, norvalyl, or ##STR2## wherein n.sub.6 is an integer of 2 to 15; A.sub.2, A.sub.3, A.sub.4 and A.sub.5 each is independently glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, or prolyl, norleucyl, or norvalyl; and n.sub.1, n.sub.2, n.sub.3, n.sub.4 and n.sub.5 each is independently 0 or 1.

  一种降解脑啡肽的氨肽酶酶被具有公式##STR1##和其药学上可接受的盐所抑制，其中R.sub.1和R.sub.2各自独立地为氢，烷基，羧基烷基，卤代烷基，羟基烷基，氨基烷基，巯基烷基，烷基硫烷基，（环烷基）烷基，（杂环基）烷基，芳基烷基，氨基甲酰基烷基，胍基烷基，或杂环芳基；R.sub.3为羟基，烷氧基，（取代烷基）氧基，芳基烷氧基，（杂环基）烷氧基或--NY.sub.1Y.sub.2，其中Y.sub.1和Y.sub.2各自独立地为氢，烷基，芳基或芳基烷基，或Y.sub.1为氢，Y.sub.2为取代烷基或（杂环基）烷基；A.sub.1为甘氨酰基，丙氨酰基，亮氨酰基，苯基丙氨酰基，精氨酰基，肌氨酰基，丝氨酰基，天冬氨酰基，赖氨酰基，谷氨酰基，组氨酰基，色氨酰基，半胱氨酰基，甲硫氨酰基，苏氨酰基，酪氨酰基，亮氨酰基，缬氨酰基，天冬酰基，脯氨酰基，诺亚亮氨酰基，或##STR2##其中n.sub.6为2到15的整数；A.sub.2、A.sub.3、A.sub.4和A.sub.5各自独立地为甘氨酰基，丙氨酰基，亮氨酰基，苯基丙氨酰基，精氨酰基，肌氨酰基，丝氨酰基，天冬氨酰基，赖氨酰基，谷氨酰基，组氨酰基，色氨酰基，半胱氨酰基，甲硫氨酰基，苏氨酰基，酪氨酰基，亮氨酰基，缬氨酰基，天冬酰基，脯氨酰基，诺亚亮氨酰基，或诺瓦林酰基；n.sub.1，n.sub.2，n.sub.3，n.sub.4和n.sub.5各自独立地为0或1。
• Renin inhibitors. Substitution of the leucyl residues of Leu-Leu-Val-Phe-OCH3 with 3-amino-2-hydroxy-5-methylhexanoic acid
  作者：Rodney L. Johnson

  DOI：10.1021/jm00347a024

  日期：1982.5

  The 2S,3S and 2R,3S diastereoisomers of the hydroxy amino acid 3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA) were synthesized and substituted for the leucyl residues of Leu-Leu-Val-Phe-OCH3 to yield the following analogues: AHMHA-Leu-Val-Phe-OCH3, AHMHA-Val-Phe-OCH3, and Leu-AHMHA-Val-Phe-OCH3. These analogues were tested in vitro for their ability to inhibit human amniotic renin. All of the analogues were found to inhibit renin to some extent with inhibitory constants in the range of 10(-3) to 10(-4) M. The analogues AHMHA-Leu-Val-Phe-OCH3 and AHMHA-Val-Phe-OCH3 exhibited competitive inhibition when the 2S,3S isomer of AHMHA was employed and noncompetitive kinetics when the 2R,3S isomer of AHMHA was used. For the Leu-AHMHA-Val-Phe-OCH3 analogues, competitive kinetics were observed regardless of the isomer of AHMHA employed. These latter analogues also proved to be the most active in the above series.