(2S)-2-{[3-(4',5'-dihydro-3'-[4"-trifluoromethyl]phenyl-5'-isoxazolyl)-2-{[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]methyl}-1-oxopropyl]amino}1H-indole-3-propanoic acid | 1198770-36-3

• 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-(4',5'-dihydro-3'-[4"-trifluoromethyl]phenyl-5'-isoxazolyl)-2-{[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]methyl}-1-oxopropyl]amino}1H-indole-3-propanoic acid
• 英文别名: (2S)-2-[[2-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]-3-[3-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid
• CAS: 1198770-36-3
• 化学式: C₄₁H₄₀F₃N₄O₈P
• 分子量: 804.76
• InChiKey: QNKOPOVZWSEPHB-KDJZUGQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  57
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  179
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  、 4-(trifluoromethyl)benzaldehyde oxime 在 吡啶 、 N-氯代丁二酰亚胺 、 三乙胺 作用下， 以 氯仿 为溶剂， 以97 mg的产率得到(2S)-2-{[3-(4',5'-dihydro-3'-[4"-trifluoromethyl]phenyl-5'-isoxazolyl)-2-{[hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]amino}ethyl)phosphinyl]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