2-sec-Butyl-4-(4-methoxy-benzylsulfanyl)-5-phenyl-pentanoic acid | 159010-24-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-sec-Butyl-4-(4-methoxy-benzylsulfanyl)-5-phenyl-pentanoic acid
• 英文别名: 2-Butan-2-yl-4-[(4-methoxyphenyl)methylsulfanyl]-5-phenylpentanoic acid
• CAS: 159010-24-9
• 化学式: C₂₃H₃₀O₃S
• 分子量: 386.555
• InChiKey: VGAGCRSQUDSCOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-sec-Butyl-4-(4-methoxy-benzylsulfanyl)-5-phenyl-pentanoic acid 在 sodium hydroxide 、 氧气 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 25.0h， 生成 2-Butan-2-yl-4-[(4-carboxy-5-methyl-1-phenylheptan-2-yl)disulfanyl]-5-phenylpentanoic acid
  参考文献：
  名称：

  New Thiol Inhibitors of Neutral Endopeptidase EC 3.4.24.11: Synthesis and Enzyme Active-Site Recognition

  摘要：

  Selective, as well as mixed, inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), are of major clinical interest in the treatment of hypertension and cardiac failure. New thiol inhibitors, corresponding to the general formula HS-CH(R(1))-CH2-CH(R(2))-CONH-CH(R(3))-COOH, were designed in order to explore the putative S-1 subsite of the active site of NEP. The inhibitors were also tested on ACE and the most representative on thermolysin (TLN) for comparison. The relatively low inhibitory potencies exhibited by these compounds (IC(50)s in the 10(-7) M range for NEP and in the 10(-6) M range for ACE) as compared to that of thiorphan (IC(50)s 2 10 X 10(-9) M on NEP and 1.40 x 10(-7) M on ACE) clearly indicate the absence of the expected energetically favorable interactions with the active site of both peptidases. A 100-fold loss of potency for these inhibitors was also observed for thermolysin as compared to thiorphan. Using the mutated Glu(102)-NEP, it was possible to demonstrate that the inhibitors do not fit the S-1 subsite of NEP but interact with the S-1' and S-2' subsites through binding of their R(1) and R(2) residues and that the C-terminal amino acid is located outside the active site. These results seem to indicate that these thiol inhibitors are not well. adapted for optimal recognition of the S-1 subsite of NEP, and probably ACE, and that other zinc-chelating moieties such as carboxylate or phosphonate groups may be preferred for this purpose.

  DOI：

  10.1021/jm00038a016
• 作为产物：
  描述：

  4-甲氧基苄硫醇 在 氢氧化钾 、 sodium tetrahydroborate 、 三甲基氯硅烷 、 氯化亚砜 、 sodium hydride 、 sodium iodide 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 乙腈 为溶剂， 反应 63.08h， 生成 2-sec-Butyl-4-(4-methoxy-benzylsulfanyl)-5-phenyl-pentanoic acid
  参考文献：
  名称：

  New Thiol Inhibitors of Neutral Endopeptidase EC 3.4.24.11: Synthesis and Enzyme Active-Site Recognition

  摘要：

  Selective, as well as mixed, inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), are of major clinical interest in the treatment of hypertension and cardiac failure. New thiol inhibitors, corresponding to the general formula HS-CH(R(1))-CH2-CH(R(2))-CONH-CH(R(3))-COOH, were designed in order to explore the putative S-1 subsite of the active site of NEP. The inhibitors were also tested on ACE and the most representative on thermolysin (TLN) for comparison. The relatively low inhibitory potencies exhibited by these compounds (IC(50)s in the 10(-7) M range for NEP and in the 10(-6) M range for ACE) as compared to that of thiorphan (IC(50)s 2 10 X 10(-9) M on NEP and 1.40 x 10(-7) M on ACE) clearly indicate the absence of the expected energetically favorable interactions with the active site of both peptidases. A 100-fold loss of potency for these inhibitors was also observed for thermolysin as compared to thiorphan. Using the mutated Glu(102)-NEP, it was possible to demonstrate that the inhibitors do not fit the S-1 subsite of NEP but interact with the S-1' and S-2' subsites through binding of their R(1) and R(2) residues and that the C-terminal amino acid is located outside the active site. These results seem to indicate that these thiol inhibitors are not well. adapted for optimal recognition of the S-1 subsite of NEP, and probably ACE, and that other zinc-chelating moieties such as carboxylate or phosphonate groups may be preferred for this purpose.

  DOI：

  10.1021/jm00038a016

文献信息

• New Thiol Inhibitors of Neutral Endopeptidase EC 3.4.24.11: Synthesis and Enzyme Active-Site Recognition
  作者：Isabel Gomez-Monterrey、Ann Beaumont、Patrick Nemecek、Bernard P. Roques、Marie-Claude Fournie-Zaluski

  DOI：10.1021/jm00038a016

  日期：1994.6

  Selective, as well as mixed, inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), are of major clinical interest in the treatment of hypertension and cardiac failure. New thiol inhibitors, corresponding to the general formula HS-CH(R(1))-CH2-CH(R(2))-CONH-CH(R(3))-COOH, were designed in order to explore the putative S-1 subsite of the active site of NEP. The inhibitors were also tested on ACE and the most representative on thermolysin (TLN) for comparison. The relatively low inhibitory potencies exhibited by these compounds (IC(50)s in the 10(-7) M range for NEP and in the 10(-6) M range for ACE) as compared to that of thiorphan (IC(50)s 2 10 X 10(-9) M on NEP and 1.40 x 10(-7) M on ACE) clearly indicate the absence of the expected energetically favorable interactions with the active site of both peptidases. A 100-fold loss of potency for these inhibitors was also observed for thermolysin as compared to thiorphan. Using the mutated Glu(102)-NEP, it was possible to demonstrate that the inhibitors do not fit the S-1 subsite of NEP but interact with the S-1' and S-2' subsites through binding of their R(1) and R(2) residues and that the C-terminal amino acid is located outside the active site. These results seem to indicate that these thiol inhibitors are not well. adapted for optimal recognition of the S-1 subsite of NEP, and probably ACE, and that other zinc-chelating moieties such as carboxylate or phosphonate groups may be preferred for this purpose.