2-acetylsulfanylmethyl-3-(naphthalen-1-yl)-butanoic acid | 415974-20-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-acetylsulfanylmethyl-3-(naphthalen-1-yl)-butanoic acid
• 英文别名: 2-(Acetylsulfanylmethyl)-3-naphthalen-1-ylbutanoic acid
• CAS: 415974-20-8
• 化学式: C₁₇H₁₈O₃S
• 分子量: 302.394
• InChiKey: RECXVLXUCCHXFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-acetylsulfanylmethyl-3-(naphthalen-1-yl)-butanoic acid 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 (S)-3-(1H-Indol-3-yl)-2-(2-mercaptomethyl-3-naphthalen-1-yl-butyrylamino)-propionic acid
  参考文献：
  名称：

  Toward an Optimal Joint Recognition of the S₁‘ Subsites of Endothelin Converting Enzyme-1 (ECE-1), Angiotensin Converting Enzyme (ACE), and Neutral Endopeptidase (NEP)

  摘要：

  The formation of vasoconstrictors (e.g., angiotensin II and endothelin) and the inactivation of vasodilators (e.g., bradykinin and atrial natriuretic) by membrane-bound zinc metallopeptidases are key mechanisms in the control of blood pressure and fluid homeostasis. The way in which these peptides modulate physiological functions has been intensively studied. With the aim to develop compounds that can jointly block the three metallopeptidases-neutral endopeptidase (NEP, neprilysin), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE-1)-we studied the common structural specificity of the S-1' subsites of these peptidases. Various mercaptoacyl amino acids of the general formula HS-CH2-CH(R-1')CO-Trp-OH, possessing more or less constrained R-1' side chains, were designed. The mercapto-acyl synthons contain one or two asymmetrical centers. The K-i values of the separated stereoisomers of the most efficient inhibitors were used to determine the stereochemical preference of each enzyme. A guideline for the joint inhibition of the three peptidases was obtained with the (2R,3R) isomer of compound 13b. Its K-i values on NEP, ACE, and ECE were 0.7, 43, and 26 nM, respectively.

  DOI：

  10.1021/jm0005454
• 作为产物：
  描述：

  2-Methylene-3-naphthalen-1-yl-butyric acid ethyl ester 在 sodium hydroxide 作用下， 以 氯仿 、 丙酮 为溶剂， 反应 24.0h， 生成 2-acetylsulfanylmethyl-3-(naphthalen-1-yl)-butanoic acid
  参考文献：
  名称：

  Toward an Optimal Joint Recognition of the S₁‘ Subsites of Endothelin Converting Enzyme-1 (ECE-1), Angiotensin Converting Enzyme (ACE), and Neutral Endopeptidase (NEP)

  摘要：

  The formation of vasoconstrictors (e.g., angiotensin II and endothelin) and the inactivation of vasodilators (e.g., bradykinin and atrial natriuretic) by membrane-bound zinc metallopeptidases are key mechanisms in the control of blood pressure and fluid homeostasis. The way in which these peptides modulate physiological functions has been intensively studied. With the aim to develop compounds that can jointly block the three metallopeptidases-neutral endopeptidase (NEP, neprilysin), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE-1)-we studied the common structural specificity of the S-1' subsites of these peptidases. Various mercaptoacyl amino acids of the general formula HS-CH2-CH(R-1')CO-Trp-OH, possessing more or less constrained R-1' side chains, were designed. The mercapto-acyl synthons contain one or two asymmetrical centers. The K-i values of the separated stereoisomers of the most efficient inhibitors were used to determine the stereochemical preference of each enzyme. A guideline for the joint inhibition of the three peptidases was obtained with the (2R,3R) isomer of compound 13b. Its K-i values on NEP, ACE, and ECE were 0.7, 43, and 26 nM, respectively.

  DOI：

  10.1021/jm0005454

文献信息

• Toward an Optimal Joint Recognition of the S₁‘ Subsites of Endothelin Converting Enzyme-1 (ECE-1), Angiotensin Converting Enzyme (ACE), and Neutral Endopeptidase (NEP)
  作者：Nicolas Inguimbert、Pascale Coric、Hervé Poras、Hervé Meudal、Franck Teffot、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm0005454

  日期：2002.3.1

  The formation of vasoconstrictors (e.g., angiotensin II and endothelin) and the inactivation of vasodilators (e.g., bradykinin and atrial natriuretic) by membrane-bound zinc metallopeptidases are key mechanisms in the control of blood pressure and fluid homeostasis. The way in which these peptides modulate physiological functions has been intensively studied. With the aim to develop compounds that can jointly block the three metallopeptidases-neutral endopeptidase (NEP, neprilysin), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE-1)-we studied the common structural specificity of the S-1' subsites of these peptidases. Various mercaptoacyl amino acids of the general formula HS-CH2-CH(R-1')CO-Trp-OH, possessing more or less constrained R-1' side chains, were designed. The mercapto-acyl synthons contain one or two asymmetrical centers. The K-i values of the separated stereoisomers of the most efficient inhibitors were used to determine the stereochemical preference of each enzyme. A guideline for the joint inhibition of the three peptidases was obtained with the (2R,3R) isomer of compound 13b. Its K-i values on NEP, ACE, and ECE were 0.7, 43, and 26 nM, respectively.