叔-丁基[(1S,2S,4R)-1,4-二苯甲基-2-羟基-5-{[(1S,2R)-2-羟基-2,3-二氢-1H-茚-1-基]氨基}-5-羰基戊基]氨基甲酸酯 | 126456-36-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 叔-丁基[(1S,2S,4R)-1,4-二苯甲基-2-羟基-5-{[(1S,2R)-2-羟基-2,3-二氢-1H-茚-1-基]氨基}-5-羰基戊基]氨基甲酸酯
• 英文名称: L-685434
• 英文别名: (2R,4S,5S)-2-benzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-N-[(1S,2R)-2-hydroxy-1-indanyl]-6-phenylhexanamide；N-[(2R)-hydroxy-(1S)-indanyl]-(5S)-{[tert-butoxycarbonyl]-amino-(4S)-hydroxy-6-phenyl-(2R)-benzyl}-hexanamide；L-685,434；L-685-434；N-(2(R)-hydroxy-1(S)-indanyl)-5(S)-(1,1-dimethylethoxycarbonylamino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethyl hexanamide；tert-butyl N-[(2S,3S,5R)-5-benzyl-3-hydroxy-6-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-6-oxo-1-phenylhexan-2-yl]carbamate
• CAS: 126456-36-8
• 化学式: C₃₃H₄₀N₂O₅
• 分子量: 544.691
• InChiKey: ZJBUCZFZQXPYFC-JOFXVPDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  40
• 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：
  108
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  叔-丁基[(1S,2S,4R)-1,4-二苯甲基-2-羟基-5-{[(1S,2R)-2-羟基-2,3-二氢-1H-茚-1-基]氨基}-5-羰基戊基]氨基甲酸酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-((1S,2R)-2-hydroxy-indan-1-ylcarbamoyl)-5-phenyl-pentyl]-carbamic acid (S)-(tetrahydro-pyran-3-yl) ester
  参考文献：
  名称：

  3-四氢呋喃和吡喃尿烷作为HIV-1蛋白酶抑制剂的高亲和力P2-配体。

  摘要：

  DOI：

  10.1021/jm00054a015
• 作为产物：
  描述：

  (3aS,8aR)-2,2-dimethyl-3-(3-phenylpropanoyl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d][1,3]oxazole 在 甲醇 、 正丁基锂 、 camphor-10-sulfonic acid 作用下， 反应 2.0h， 生成 叔-丁基[(1S,2S,4R)-1,4-二苯甲基-2-羟基-5-{[(1S,2R)-2-羟基-2,3-二氢-1H-茚-1-基]氨基}-5-羰基戊基]氨基甲酸酯
  参考文献：
  名称：

  Highly diastereoselective alkylations of chiral amide enolates: new routes to hydroxyethylene dipeptide isostere inhibitors of HIV-1 protease

  摘要：

  The nonchelate enforced chiral amide enolates derived from 4-7 react with alkyl iodide and protected alpha-amino epoxide electrophiles to produce the HIV protease inhibitors 10 and 16-19 with high diastereoselectivity.

  DOI：

  10.1021/jo00036a004

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。
• Allyltrichlorostannane Additions to α-Amino Aldehydes: Application to the Total Synthesis of the Aspartyl Protease Inhibitors<scp>l</scp>-682,679,<scp>l</scp>-684,414,<scp>l</scp>-685,434, and<scp>l</scp>-685,458
  作者：Luiz C. Dias、Gaspar Diaz、Andrea A. Ferreira、Paulo R. Meira、Edílson Ferreira

  DOI：10.1055/s-2003-37649

  日期：——

  The hydroxyethylene dipeptide isosteres l-682,679, l-684,414, l-685,434, and l-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-syn and 1,2-anti amino alcohols to give the diols, lactonization under TPAP conditions, lactone opening, and peptide coupling with the desired amine or dipeptide amide. The present synthetic approach represents a practical entry to a large range of other dipeptide isosteres.

  羟基亚乙基二肽等排体l-682,679、l-684,414、l-685,434和l-685,458通过一系列步骤合成，包括与α-氨基醛的烯丙基三氯锡烷偶联、相应的1,2-顺式和1,2-反式氨基醇的氢硼化反应生成二醇、在TPAP条件下内酯化、内酯开环以及与所需胺或二肽酰胺的肽偶联。这种合成方法为其他大量二肽等排体的制备提供了一条实用的途径。
• Short Total Synthesis of Aspartyl Protease Inhibitors L-685,434, L-682,679 and L-685,458
  作者：Luiz C. Dias、Andrea A. Ferreira、Gaspar Diaz

  DOI：10.1055/s-2002-34891

  日期：——

  Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti aminoalcohols to give the diols, lactonization under TPAP conditions, lactone opening and peptide coupling with the desired amine or dipeptide amide.

  羟乙基二肽等效体L-685,434、L-682,679和L-685,458通过一系列步骤合成，包括与烯丙基三氯锡烷的偶联反应生成α-氨基醛，随后对相应的1,2-顺式和1,2-反式氨基醇进行硼氢化反应生成二醇，在TPAP条件下内酯化，内酯开环并与所需胺或二肽酰胺进行肽偶联反应。
• Methods and compositions for the treatment or prevention of human immunodeficiency virus and related conditions using cyclooxygenase-2 selective inhibitors and antiviral agents
  申请人：Maziasz Timothy

  公开号：US20050026902A1

  公开（公告）日：2005-02-03

  The present invention provides compositions and methods for the treatment of human immunodeficiency virus (HIV) infection as well as HIV associated diseases and related disorders. More particularly, the invention provides a combination therapy for the treatment of HIV infection as well as HIV associated diseases and related disorders comprising the administration to a subject of an anti-human immunodeficiency virus agent in combination with a cyclooxygenase-2 selective inhibitor or an isomer or a pharmaceutically acceptable salt, ester, or prodrug thereof.

  本发明提供了治疗人类免疫缺陷病毒（HIV）感染以及HIV相关疾病和相关紊乱的组合物和方法。更具体地说，本发明提供了一种治疗HIV感染以及HIV相关疾病和相关紊乱的组合疗法，包括向受试者施用抗人类免疫缺陷病毒制剂与环氧化酶-2选择性抑制剂或其异构体或其药学上可接受的盐、酯或原药组合。
• 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.