(S)-1-((3aS,8aR)-2,2-Dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-pyridin-3-ylmethyl-pent-4-en-1-one | 342600-62-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (S)-1-((3aS,8aR)-2,2-Dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-pyridin-3-ylmethyl-pent-4-en-1-one
• 英文别名: (2S)-1-[(3aR,8bS)-2,2-dimethyl-4,8b-dihydro-3aH-indeno[1,2-d][1,3]oxazol-1-yl]-2-(pyridin-3-ylmethyl)pent-4-en-1-one
• CAS: 342600-62-8
• 化学式: C₂₃H₂₆N₂O₂
• 分子量: 362.472
• InChiKey: KYPZOMBFASANCH-TYPHKJRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-((3aS,8aR)-2,2-Dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-pyridin-3-ylmethyl-pent-4-en-1-one 在 咪唑 、 盐酸 、 lithium hydroxide 、 甲烷磺酸 、 水 、 碘 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 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 59.1h， 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-(3-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：

  N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-pyridin-3-ylpropanamide 在 camphor-10-sulfonic acid 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (S)-1-((3aS,8aR)-2,2-Dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-pyridin-3-ylmethyl-pent-4-en-1-one
  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 and uses thereof
  申请人：Merck & Co., Inc.

  公开号：US06642237B1

  公开（公告）日：2003-11-04

  &ggr;-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds are inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.

  -Hydroxy-2-(氟烷基氨基甲酰)-1-哌嗪戊二酰胺化合物是HIV蛋白酶的抑制剂，也是HIV复制的抑制剂。这些化合物在预防或治疗HV感染以及治疗艾滋病方面非常有用，无论是作为化合物、药学上可接受的盐、药物组成成分，还是与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。这些化合物对目前用于治疗艾滋病和HIV感染的HIV蛋白酶抑制剂产生耐药性的HIV病毒突变体具有有效作用。
• 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
• 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.