(2S)-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino]-5-oxo-4-(pyridin-4-ylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide | 342600-75-3

• 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)-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino]-5-oxo-4-(pyridin-4-ylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
• CAS: 342600-75-3
• 化学式: C₂₇H₃₄F₃N₅O₅
• 分子量: 565.593
• InChiKey: TUYQNRYYMBXVTD-JUZIDSRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  136
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-苯基-2-糠醛 、 (2S)-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino]-5-oxo-4-(pyridin-4-ylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (αR,γS,2S)-N-((3S,4S)-3,4-dihydro-3-hydroxy-2H-1-benzopyran-4-yl)-γ-hydroxy-4-[(5-phenyl-2-furanyl)methyl]-α-(4-pyridinylmethyl)-2-[[(2,2,2-trifluoroethyl)amino]carbonyl]-1-piperazinepentanamide
  参考文献：
  名称：

  HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent

  摘要：

  Transposition of the pyridyl nitrogen from the P-3 substituent to the P-1' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00680-2
• 作为产物：
  描述：

  3-吡啶-4-基-丙酸 在 咪唑 、 盐酸 、 lithium hydroxide 、 甲烷磺酸 、 camphor-10-sulfonic acid 、 水 、 碘 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 64.6h， 生成 (2S)-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino]-5-oxo-4-(pyridin-4-ylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
  参考文献：
  名称：

  HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent

  摘要：

  Transposition of the pyridyl nitrogen from the P-3 substituent to the P-1' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00680-2

文献信息

• HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent
  作者：Joseph L. Duffy、Brian A. Kirk、Nancy J. Kevin、Kevin T. Chapman、William A. Schleif、David B. Olsen、Mark Stahlhut、Carrie A. Rutkowski、Lawrence C. Kuo、Lixia Jin、Jiunn H. Lin、Emilio A. Emini、James R. Tata

  DOI：10.1016/s0960-894x(03)00680-2

  日期：2003.10

  Transposition of the pyridyl nitrogen from the P-3 substituent to the P-1' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.