N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-[1,1-dimethylethoxy-carbonylamino]-4(S)-hydroxy-6-phenyl-2(R)-(4-hydroxyphenylmethyl) hexanamide | 138498-62-1

• 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-dimethylethoxy-carbonylamino]-4(S)-hydroxy-6-phenyl-2(R)-(4-hydroxyphenylmethyl) hexanamide
• 英文别名: N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2(R)-[(4-hydroxyphenyl)methyl]hexanamide；[1-Benzyl-2-hydroxy-4-(2-hydroxy-indan-1-ylcarbamoyl)-5-(4-hydroxy-phenyl)-pentyl]-carbamic acid tert-butyl ester；tert-butyl N-[(2S,3S,5R)-3-hydroxy-6-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-[(4-hydroxyphenyl)methyl]-6-oxo-1-phenylhexan-2-yl]carbamate
• CAS: 138498-62-1
• 化学式: C₃₃H₄₀N₂O₆
• 分子量: 560.69
• InChiKey: IXMOCJVKYIUCEJ-BANMPPSNSA-N

物化性质

• 沸点：
  834.0±65.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  128
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-[1,1-dimethylethoxy-carbonylamino]-4(S)-hydroxy-6-phenyl-2(R)-(4-hydroxyphenylmethyl) hexanamide 在 锂硼氢 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 为溶剂， 反应 26.0h， 生成 N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-<(tert-butyloxycarbonyl)amino>-4(S)-hydroxy-6-phenyl-2(R)-<<4-(2-hydroxyethoxy)phenyl>methyl>hexanamide
  参考文献：
  名称：

  一系列具有与P1或P1'苯基取代基相连的功能的HIV-1蛋白酶抑制剂的合成和抗病毒活性：X射线晶体结构辅助设计。

  摘要：

  通过将极性亲水基团束缚到基于Phe的羟乙烯等排物的P1或P1'取代基上，一系列HIV蛋白酶抑制剂的抗病毒效力得到了提高。用4-吗啉基乙氧基取代基观察到抗HIV活性的最佳增强。取代基效应与衍生自停泊在天然酶的晶体结构中的抑制剂的模型一致。确定为2.25 A的抑制酶的X射线晶体结构验证了模型预测。

  DOI：

  10.1021/jm00088a003
• 作为产物：
  描述：

  4-(bromomethyl)phenol 在 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 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 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 122.0h， 生成 N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-[1,1-dimethylethoxy-carbonylamino]-4(S)-hydroxy-6-phenyl-2(R)-(4-hydroxyphenylmethyl) hexanamide
  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 useful for the treatment of aids
  申请人：MERCK & CO. INC.

  公开号：EP0534511A1

  公开（公告）日：1993-03-31

  Compounds of the form,         A-G-J    wherein A is an amine protecting group or urethane, G a dipeptide isostere and J a small terminal group are described. They are distinguished by tetrahydrofuryl or tetrahydropyranyl substituents, and the like. These compounds are useful in the inhibition of HIV 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.

  形式为A-G-J的化合物被描述，其中A是胺保护基或脲醚，G是二肽同分异构体，J是小的末端基团。它们以四氢呋喃基或四氢吡喃基取代等方式进行区分。这些化合物在抑制HIV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、药用组合成分，还是与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。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。
• Inhibitors of HIV protease
  申请人：MERCK & CO. INC.

  公开号：EP0480711A1

  公开（公告）日：1992-04-15

  A dipeptide isostere is the biotransformed product after incubation with a culture of Streptomyces. It inhibits HIV protease, and is useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  二肽同分异构体是在与链霉菌培养物孵育后的生物转化产物。它抑制HIV蛋白酶，在预防或治疗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、药用组合成分，无论是否作为前药或与其他抗病毒药物、抗感染剂、免疫调节剂、抗生素或疫苗的组合。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 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。
• Method of hydroxylation with ATCC 55086
  申请人：Merck & Co., Inc.

  公开号：US05187074A1

  公开（公告）日：1993-02-16

  A novel dipeptide isostere is the biotransformed product after incubation with a culture of Streptomyces. It inhibits HIV protease, and is useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  一种新的二肽类同构体是在与链霉菌培养物孵育后的生物转化产物。它能抑制HIV蛋白酶，对预防或治疗HIV感染以及治疗艾滋病具有用处，无论是作为化合物、药用盐、药用成分，还是作为前药或与其他抗病毒药物、抗感染药物、免疫调节剂、抗生素或疫苗的组合物。还描述了治疗艾滋病和预防或治疗HIV感染的方法。
• Method of preparing HIV protease inhibitors
  申请人：Merck & Co., Inc.

  公开号：US05188950A1

  公开（公告）日：1993-02-23

  Novel dipeptide isosteres are the biotransformed products after incubation with rat liver slices. They inhibit HIV protease, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts (when appropriate), pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  小说二肽同位素是在与大鼠肝脏切片孵育后生物转化的产物。它们可以抑制HIV蛋白酶，并且作为化合物、药学上可接受的盐（如果适用）、药物组成成分，无论是否与其他抗病毒药物、抗感染药物、免疫调节剂、抗生素或疫苗组合使用，都可用于预防或治疗HIV感染和治疗艾滋病。还描述了治疗艾滋病和预防或治疗HIV感染的方法。