(2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)-3-phenyl propanoic acid | 908607-44-3

• 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]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)-3-phenyl propanoic acid
• 英文别名: (2S)-2-[[(2R)-2-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoyl]amino]-3-phenylpropanoic acid
• CAS: 908607-44-3
• 化学式: C₃₈H₃₈N₃O₈P
• 分子量: 695.709
• InChiKey: YJNWDJIIFRGLRO-FFYHKYONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  [3-[[(2S)-1-[(2-methylpropan-2-yl)oxy]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propyl]-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)-3-phenyl propanoic acid 、 (2S)-2-({3-[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)-3-phenyl 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

文献信息

• Phosphinic Amino Acid Compounds
  申请人：Dive Vincent

  公开号：US20080153890A1

  公开（公告）日：2008-06-26

  Compounds of formula (I): wherein: R 1 represents hydrogen, alkylcarbonyloxyalkyl or alkylcarbonylthioalkyl, R 2 represents hydrogen, alkylcarbonyloxyalkyl, arylcarbonylthioalkyl or optionally substituted arylalkyl, R 3 represents phenyl, which is optionally substituted, or indolyl, their isomers, and addition salts thereof with a pharmaceutically acceptable acid or base. Medicinal products containing the same which are useful in the treatment of arterial hypertension and complications thereof.

  式(I)的化合物：其中：R1代表氢、烷基羰基氧烷基或烷基羰基硫烷基，R2代表氢、烷基羰基氧烷基、芳基羰基硫烷基或可选择取代的芳基烷基，R3代表苯基（可选择取代）或吲哚基，它们的异构体以及与药学上可接受的酸或碱形成的加合物。含有这些化合物的药物，用于治疗动脉高血压及其并发症。
• US7521469B2
  申请人：——

  公开号：US7521469B2

  公开（公告）日：2009-04-21
• 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.