(2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]-amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)1H-indole-3-propanoic acid methyl ester | 1198770-47-6

• 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: (2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]-amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)1H-indole-3-propanoic acid methyl ester
• 英文别名: [(2S)-3-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-3-oxo-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propyl]-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 1198770-47-6
• 化学式: C₄₁H₄₁N₄O₈P
• 分子量: 748.772
• InChiKey: FBAHTKHKCAFHKZ-YRUAXCGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  54
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]-amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)1H-indole-3-propanoic acid methyl ester 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以86%的产率得到(2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)1H-indole-3-propanoic acid
  参考文献：
  名称：

  Phosphinic Tripeptides as Dual Angiotensin-Converting Enzyme C-Domain and Endothelin-Converting Enzyme-1 Inhibitors

  摘要：

  A new series of phosphinic inhibitors able to interact with both angiotensin-converting enzyme (ACE) C-domain and endothelin-converting enzyme-1 (ECE-1), while sparing neprilysin (NEP), has been developed. The most potent and selective inhibitor in this series (compound 8(F2)) displays K-i values of 0.65 nM, 150 nM, 14 nM and 6.7 mu M toward somatic ACE C-domain, ACE N-domain, ECE-1, and NEP, respectively. Remarkably, in this series, the inhibitor's ability to discriminate between ECE-1 and NEP was observed to depend oil the stereochemistry of the residue present in the inhibitor's P-1' position. After iv administration, compound 8(F2) (10 mg/kg) lowered mean arterial blood pressure by 24 +/- 2 mmHg in spontaneously hypertensive rats, as compared with controls. Mixed ACE/ECE-1 inhibitor may lead to a new generation of vasopeptide inhibitors that should reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage.

  DOI：

  10.1021/jm9010803
• 作为产物：
  描述：

  (1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl[(2S)-2-({[(1S)-1-(1H-indol-3-ylmethyl)-2-methoxy-2-oxoethyl]amino}carbonyl)-pent-4-ynyl]phosphinic acid 、 苯甲醛肟 在 吡啶 、 N-氯代丁二酰亚胺 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 3.17h， 以70%的产率得到(2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]-amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)1H-indole-3-propanoic acid methyl ester
  参考文献：
  名称：

  Phosphinic Tripeptides as Dual Angiotensin-Converting Enzyme C-Domain and Endothelin-Converting Enzyme-1 Inhibitors

  摘要：

  A new series of phosphinic inhibitors able to interact with both angiotensin-converting enzyme (ACE) C-domain and endothelin-converting enzyme-1 (ECE-1), while sparing neprilysin (NEP), has been developed. The most potent and selective inhibitor in this series (compound 8(F2)) displays K-i values of 0.65 nM, 150 nM, 14 nM and 6.7 mu M toward somatic ACE C-domain, ACE N-domain, ECE-1, and NEP, respectively. Remarkably, in this series, the inhibitor's ability to discriminate between ECE-1 and NEP was observed to depend oil the stereochemistry of the residue present in the inhibitor's P-1' position. After iv administration, compound 8(F2) (10 mg/kg) lowered mean arterial blood pressure by 24 +/- 2 mmHg in spontaneously hypertensive rats, as compared with controls. Mixed ACE/ECE-1 inhibitor may lead to a new generation of vasopeptide inhibitors that should reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage.

  DOI：

  10.1021/jm9010803

文献信息

• Phosphinic Tripeptides as Dual Angiotensin-Converting Enzyme C-Domain and Endothelin-Converting Enzyme-1 Inhibitors
  作者：Nicolas Jullien、Anastasios Makritis、Dimitris Georgiadis、Fabrice Beau、Athanasios Yiotakis、Vincent Dive

  DOI：10.1021/jm9010803

  日期：2010.1.14

  A new series of phosphinic inhibitors able to interact with both angiotensin-converting enzyme (ACE) C-domain and endothelin-converting enzyme-1 (ECE-1), while sparing neprilysin (NEP), has been developed. The most potent and selective inhibitor in this series (compound 8(F2)) displays K-i values of 0.65 nM, 150 nM, 14 nM and 6.7 mu M toward somatic ACE C-domain, ACE N-domain, ECE-1, and NEP, respectively. Remarkably, in this series, the inhibitor's ability to discriminate between ECE-1 and NEP was observed to depend oil the stereochemistry of the residue present in the inhibitor's P-1' position. After iv administration, compound 8(F2) (10 mg/kg) lowered mean arterial blood pressure by 24 +/- 2 mmHg in spontaneously hypertensive rats, as compared with controls. Mixed ACE/ECE-1 inhibitor may lead to a new generation of vasopeptide inhibitors that should reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage.