(5R,6R)-1,5-Dibenzyl-2-cyclopropylmethyl-6-hydroxy-4-(4-hydroxy-3-methoxy-benzyl)-[1,2,4]triazepan-3-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (5R,6R)-1,5-Dibenzyl-2-cyclopropylmethyl-6-hydroxy-4-(4-hydroxy-3-methoxy-benzyl)-[1,2,4]triazepan-3-one
• 英文别名: (5R,6R)-1,5-dibenzyl-2-(cyclopropylmethyl)-6-hydroxy-4-[(4-hydroxy-3-methoxyphenyl)methyl]-1,2,4-triazepan-3-one
• 化学式: C₃₀H₃₅N₃O₄
• 分子量: 501.626
• InChiKey: ZXMNXYSILSXVSY-IXCJQBJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  76.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-Cbz-D-苯丙氨醛 在 palladium on activated charcoal 三甲基氯硅烷 、 氢气 、 sodium hydride 、 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 119.75h， 生成 (5R,6R)-1,5-Dibenzyl-2-cyclopropylmethyl-6-hydroxy-4-(4-hydroxy-3-methoxy-benzyl)-[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

• 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.