(5R,6R)-1,5-Dibenzyl-6-(2-trimethylsilanyl-ethoxymethoxy)-[1,2,4]triazepan-3-one | 173261-25-1

• 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: (5R,6R)-1,5-Dibenzyl-6-(2-trimethylsilanyl-ethoxymethoxy)-[1,2,4]triazepan-3-one
• 英文别名: (5R,6R)-1,5-dibenzyl-6-(2-trimethylsilylethoxymethoxy)-1,2,4-triazepan-3-one
• CAS: 173261-25-1
• 化学式: C₂₄H₃₅N₃O₃Si
• 分子量: 441.646
• InChiKey: UJMWYGUNHHXVBE-DHIUTWEWSA-N

物化性质

• 密度：
  1.12±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  62.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5R,6R)-1,5-Dibenzyl-6-(2-trimethylsilanyl-ethoxymethoxy)-[1,2,4]triazepan-3-one 在 palladium dihydroxide 吡啶 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (5R,6R)-1-(3-Benzo[1,3]dioxol-5-yl-propionyl)-5-benzyl-6-(2-trimethylsilanyl-ethoxymethoxy)-[1,2,4]triazepan-3-one
  参考文献：
  名称：

  Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains

  摘要：

  As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.

  DOI：

  10.1016/j.bmcl.2005.08.093
• 作为产物：
  描述：

  N-Cbz-D-苯丙氨醛 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 118.5h， 生成 (5R,6R)-1,5-Dibenzyl-6-(2-trimethylsilanyl-ethoxymethoxy)-[1,2,4]triazepan-3-one
  参考文献：
  名称：

  A Novel, Picomolar Inhibitor of Human Immunodeficiency Virus Type 1 Protease

  摘要：

  The design, synthesis, and molecular modeling studies of a novel series of azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV-1) protease that incorporate different ligands for the S1', S2, and S2' substrate-binding sites of HIV-1 protease are described. The synthesis of this series is highly flexible in the sense that the P1', P2, and P2' residues of the inhibitors can be changed independently. Molecular modeling studies on the phenyl ring of the P2 and P2' ligand suggested incorporation of hydrogen-bonding donor/acceptor groups at the 3' and 4-positions of the phenyl ring should increase binding potency. This led to the discovery of compound 7f (A-98881), which possesses high potency in the HIV-1 protease inhibition assay and the in vitro MT-4 cell culture assay (Ki = approximately 5 pM and EC50 = 0.002 microM). This compares well with the symmetrical cyclic urea 1 pioneered at DuPont Merck.

  DOI：

  10.1021/jm9507183

文献信息

• Synthesis and antiviral activity of P1′ arylsulfonamide azacyclic urea HIV protease inhibitors
  作者：Peggy P Huang、John T Randolph、Larry L Klein、Sudthida Vasavanonda、Tatyana Dekhtyar、Vincent S Stoll、Dale J Kempf

  DOI：10.1016/j.bmcl.2004.05.036

  日期：2004.8

  A series of novel azacyclic urea HIV protease inhibitors bearing a benzenesulfonamide group at P1' were synthesized utilizing a parallel synthesis method. Structural studies of early analogs bound in the enzyme active site were used to design more potent inhibitors. The effects of substituting the P1' benzenesulfonyl group on antiviral activity and protein binding are described.

  使用平行合成方法合成了一系列在P1'处带有苯磺酰胺基团的新型氮杂环尿素HIV蛋白酶抑制剂。结合在酶活性位点上的早期类似物的结构研究被用于设计更有效的抑制剂。描述了取代P1'苯磺酰基对抗病毒活性和蛋白质结合的影响。
• A Novel, Picomolar Inhibitor of Human Immunodeficiency Virus Type 1 Protease
  作者：Hing L. Sham、Chen Zhao、Kent D. Stewart、David A. Betebenner、Shuqun Lin、Chang H. Park、Xiang-P. Kong、William Rosenbrook、Thomas Herrin、Darold Madigan、Suthida Vasavanonda、Nicholas Lyons、Akhter Molla、Ayda Saldivar、Kennan C. Marsh、Edith McDonald、Norman E. Wideburg、Jon F. Denissen、Terrel Robins、Dale J. Kempf、Jacob J. Plattner、Daniel W. Norbeck

  DOI：10.1021/jm9507183

  日期：1996.1.1

  The design, synthesis, and molecular modeling studies of a novel series of azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV-1) protease that incorporate different ligands for the S1', S2, and S2' substrate-binding sites of HIV-1 protease are described. The synthesis of this series is highly flexible in the sense that the P1', P2, and P2' residues of the inhibitors can be changed independently. Molecular modeling studies on the phenyl ring of the P2 and P2' ligand suggested incorporation of hydrogen-bonding donor/acceptor groups at the 3' and 4-positions of the phenyl ring should increase binding potency. This led to the discovery of compound 7f (A-98881), which possesses high potency in the HIV-1 protease inhibition assay and the in vitro MT-4 cell culture assay (Ki = approximately 5 pM and EC50 = 0.002 microM). This compares well with the symmetrical cyclic urea 1 pioneered at DuPont Merck.
• Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains
  作者：Chen Zhao、Hing L. Sham、Minghua Sun、Vincent S. Stoll、Kent D. Stewart、Shuqun Lin、Hongmei Mo、Sudthida Vasavanonda、Ayda Saldivar、Chang Park、Edith J. McDonald、Kennan C. Marsh、Larry L. Klein、Dale J. Kempf、Daniel W. Norbeck

  DOI：10.1016/j.bmcl.2005.08.093

  日期：2005.12

  As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.