N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-(1,1-dimethylethoxycarbonyl)amino-4(S)-hydroxy-6-phenyl-2(R)-(4-(3-(2-methoxyethoxy)methoxypropyl)-phenyl)methylhexanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-(1,1-dimethylethoxycarbonyl)amino-4(S)-hydroxy-6-phenyl-2(R)-(4-(3-(2-methoxyethoxy)methoxypropyl)-phenyl)methylhexanamide
• 英文别名: N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-{[(1,1-dimethylethoxy)carbonyl]amino}-4(S)-hydroxy-6-phenyl-2(R)-[(4-{3-[(2-methoxyethoxy)methoxy]propyl}phenyl)methyl]hexanamide；tert-butyl N-[(1S,2S,4R)-1-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxyindan-1-yl]amino]-4-[[4-[3-(2-methoxyethoxymethoxy)propyl]phenyl]methyl]-5-oxo-pentyl]carbamate；tert-butyl N-[(2S,3S,5R)-3-hydroxy-6-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-[[4-[3-(2-methoxyethoxymethoxy)propyl]phenyl]methyl]-6-oxo-1-phenylhexan-2-yl]carbamate
• 化学式: C₄₀H₅₄N₂O₈
• 分子量: 690.877
• InChiKey: AROGOLUHMWJZII-VCPMIQRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  50
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(4-羟基甲基苯基)-1-丙醇 在 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 氢溴酸 、 sodium ethanolate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 166.0h， 生成 N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-(1,1-dimethylethoxycarbonyl)amino-4(S)-hydroxy-6-phenyl-2(R)-(4-(3-(2-methoxyethoxy)methoxypropyl)-phenyl)methylhexanamide
  参考文献：
  名称：

  HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

  摘要：

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.

  DOI：

  10.1021/jm00088a004

文献信息

• HIV protease inhibitors having polyether substituents
  申请人：MERCK & CO. INC.

  公开号：EP0487270A2

  公开（公告）日：1992-05-27

  Polyether derivatives of the form,         A-G-B-B-J    wherein G is a dipeptide isostere substituted with a polyether, B an amino acid or analog thereof, and J a small terminal group are described. These compounds are useful in the inhibition of DIV protease, the prevention or treatment of infection by HIV 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.

  描述了形式为A-G-B-B-J的聚醚衍生物，其中G是用聚醚取代的二肽同分异构体，B是氨基酸或其类似物，J是一个小的末端基团。这些化合物在抑制DIV蛋白酶、预防或治疗HIV感染以及治疗艾滋病方面具有用途，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。
• HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity
  作者：Steven D. Young、Linda S. Payne、Wayne J. Thompson、Neil Gaffin、Terry A. Lyle、Susan F. Britcher、Samuel L. Graham、Thomas H. Schultz、Albert A. Deana

  DOI：10.1021/jm00088a004

  日期：1992.5

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.