(2S,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid | 96813-06-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (2S,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid
• 英文别名: (2s,4s,5s)-5-(t-Butoxycarbonylamino)-4-hydroxy-2-isopropyl-7-methyloctanoic acid；(2S,4S,5S)-4-hydroxy-7-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-propan-2-yloctanoic acid
• CAS: 96813-06-8
• 化学式: C₁₇H₃₃NO₅
• 分子量: 331.453
• InChiKey: QITGDTSFWCYBEE-IHRRRGAJSA-N

物化性质

• 沸点：
  485.4±40.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid 在 盐酸 、 氰基磷酸二乙酯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl N-[(2S)-1-[[(2S)-1-[[(4S,5S,7S)-5-hydroxy-2,8-dimethyl-7-[[(2S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]carbamoyl]nonan-4-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  构象受限的肾素抑制肽：γ-内酰胺桥联的二肽等排体作为构象限制。

  摘要：

  人肾素的酶结合抑制剂的构象模型表明在P2-P3位点存在γ-内酰胺构象限制的可能性。描述了这些γ-内酰胺二肽等排体的合成途径及其掺入潜在的肾素抑制剂中。具有γ-内酰胺构象约束和在裂解位点处的羟乙烯等排物的肽VIa，b抑制人血浆肾素，IC 50值为6.5 nM。这些合成方法的灵活性应为研究酶结合构象异构体提供许多具有这种结构特征的潜在酶抑制剂。

  DOI：

  10.1021/jm00402a021
• 作为产物：
  描述：

  (2R,4S,5S)-2-(2-propyl)-4-hydroxy-5-<(tert-butyloxycarbonyl)amino>-7-methyloctanoic acid δ-lactone 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid
  参考文献：
  名称：

  Design of Substrate-Based Inhibitors of Human β-Secretase

  摘要：

  By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P-l resulted in a weak inhibitor 13 of the enzyme. Further substitution of P-1'-Asp by P-1'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P-10-P-5 residues on the N-terminal part of inhibitor 22 resulted in no loss of potency (23). C-terminal truncations of inhibitor 22 generally led to significant loss of potency.

  DOI：

  10.1021/jm0155695

文献信息

• Peptides
  申请人：THE UPJOHN COMPANY

  公开号：EP0173481A2

  公开（公告）日：1986-03-05

  Novel peptides which can act to inhibit renin and can have utility in the diagnosis and control of renin-dependent hypertension, and intermediates in the preparation of both the new and known renin-inhibiting peptides.

  可抑制肾素并可用于诊断和控制肾素依赖性高血压的新型肽，以及制备新型和已知肾素抑制肽的中间体。
• Renin-inhibiting peptides
  申请人：THE UPJOHN COMPANY

  公开号：EP0486478A2

  公开（公告）日：1992-05-20

  A renin inhibitory peptide comprising a N-alkylhistidine moiety at the position corresponding to the 9-position of the human renin substrate.

  一种肾素抑制肽，在与人类肾素底物 9 位相对应的位置上包含一个 N-烷基组氨酸分子。
• On a Possible Neutral Charge State for the Catalytic Dyad in β-Secretase When Bound to Hydroxyethylene Transition State Analogue Inhibitors
  作者：Fredy Sussman、José M. Otero、M. Carmen Villaverde、Marian Castro、José L. Domínguez、Lucía González-Louro、Ramón J. Estévez、J. Carlos Estévez

  DOI：10.1021/jm101568y

  日期：2011.4.28

  beta-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients Our previous results using a combination of surface plasmon resonance experiments with molecular Modeling calculations: suggested that the Asp dyad in beta-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.
• THAISRIVONGS, SUVIT;PALS, DONALD T.;TURNER, STEVE R.;KROLL, LISA T., J. MED. CHEM., 31,(1988) N 7, 1369-1376
  作者：THAISRIVONGS, SUVIT、PALS, DONALD T.、TURNER, STEVE R.、KROLL, LISA T.

  DOI：——

  日期：——
• US4880781A
  申请人：——

  公开号：US4880781A

  公开（公告）日：1989-11-14