(S)-1-[(2S,4R)-2-Hydroxy-4-((3S,4S)-3-hydroxy-chroman-4-ylcarbamoyl)-5-pyridin-3-yl-pentyl]-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide | 342600-66-2

• 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: (S)-1-[(2S,4R)-2-Hydroxy-4-((3S,4S)-3-hydroxy-chroman-4-ylcarbamoyl)-5-pyridin-3-yl-pentyl]-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
• 英文别名: (2R,4S)-N-[(3S)-3beta-Hydroxy-3,4-dihydro-2H-1-benzopyran-4beta-yl]-2-(3-pyridinylmethyl)-4-hydroxy-5-[(2S)-2alpha-(2,2,2-trifluoroethylcarbamoyl)piperazino]pentanamide；(2S)-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino]-5-oxo-4-(pyridin-3-ylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
• CAS: 342600-66-2
• 化学式: C₂₇H₃₄F₃N₅O₅
• 分子量: 565.593
• InChiKey: HHRDYIRKBHIZBK-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：

  1-(2-氟苯基)-1H-吡咯-3-甲醛 、 (S)-1-[(2S,4R)-2-Hydroxy-4-((3S,4S)-3-hydroxy-chroman-4-ylcarbamoyl)-5-pyridin-3-yl-pentyl]-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide 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 1.0h， 生成 (2S)-4-[[1-(2-fluorophenyl)pyrrol-3-yl]methyl]-1-[(2S,4R)-2-hydroxy-5-[[(3S,4S)-3-hydroxychroman-4-yl]amino]-5-oxo-4-(3-pyridylmethyl)pentyl]-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide
  参考文献：
  名称：

  Novel HIV-1 protease inhibitors active against multiple PI-Resistant viral strains: coadministration with indinavir

  摘要：

  HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P-3 position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.049
• 作为产物：
  描述：

  1-[(3aR,8bS)-2,2-dimethyl-4,8b-dihydro-3aH-indeno[1,2-d][1,3]oxazol-1-yl]-3-pyridin-3-ylpropan-1-one 在 咪唑 、 盐酸 、 lithium hydroxide 、 甲烷磺酸 、 水 、 碘 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 59.6h， 生成 (S)-1-[(2S,4R)-2-Hydroxy-4-((3S,4S)-3-hydroxy-chroman-4-ylcarbamoyl)-5-pyridin-3-yl-pentyl]-piperazine-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
  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

• GAMMA-HYDROXY-2-(FLUOROALKYLAMINOCARBONYL)-1-PIPERAZINEPENTANAMIDES AS HIV PROTEASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1242426B1

  公开（公告）日：2007-10-31
• Novel HIV-1 protease inhibitors active against multiple PI-Resistant viral strains: coadministration with indinavir
  作者：Nancy J. Kevin、Joseph L. Duffy、Brian A. Kirk、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/j.bmcl.2003.08.049

  日期：2003.11

  HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P-3 position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment. (C) 2003 Elsevier Ltd. All rights reserved.
• 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.