(4R,5S,6S,7R)-1,3-Bis-(3-amino-1H-indazol-5-ylmethyl)-4,7-dibenzyl-5,6-dihydroxy-[1,3]diazepan-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (4R,5S,6S,7R)-1,3-Bis-(3-amino-1H-indazol-5-ylmethyl)-4,7-dibenzyl-5,6-dihydroxy-[1,3]diazepan-2-one
• 英文别名: (4R,5S,6S,7R)-1,3-bis[(3-amino-1H-indazol-5-yl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one
• 化学式: C₃₅H₃₆N₈O₃
• 分子量: 616.723
• InChiKey: SNDNVFWPJDWEQH-ZRTHHSRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  46
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  173
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4R,5S,6S,7R)-hexahydro-5,6-O-isopropylidene-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one 在 盐酸 、 potassium tert-butylate 、 一水合肼 作用下， 以 四氢呋喃 、 甲醇 、 正丁醇 为溶剂， 生成 (4R,5S,6S,7R)-1,3-Bis-(3-amino-1H-indazol-5-ylmethyl)-4,7-dibenzyl-5,6-dihydroxy-[1,3]diazepan-2-one
  参考文献：
  名称：

  Increased antiviral activity of cyclic urea HIV protease inhibitors by modifying the P1/P1′ substituents

  摘要：

  A series of alkyl substituted P1/P1' analogs was prepared in an attempt to increase translation of the 3-aminoindazole class of HIV protease inhibitors. Increasing the lipophilicity of the P1/P1' residues dramatically improved translation of enzyme activity to antiviral activity in the whole cell assay. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00367-4

文献信息

• Potent cyclic urea HIV protease inhibitors with 3-aminoindazole P2/P2′ groups
  作者：James D. Rodgers、Barry L. Johnson、Wang Haisheng、Susan Erickson-Viitanen、Ronald M. Klabe、Lee Bacheler、Beverly C. Cordova、Chong-Hwan Chang

  DOI：10.1016/s0960-894x(98)00118-8

  日期：1998.4

  Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.

  含有3-氨基吲唑P2 / P2'基团的环状脲是极强的HIV蛋白酶抑制剂。母体3-氨基吲唑6显示Ki ＜0.01nM，但是观察到酶活性向抗病毒活性的差的翻译。一系列3-烷基氨基吲唑显示，随着亲脂性的提高，翻译效果也得到改善。获得与HIV蛋白酶结合的6的X射线晶体结构。
• Increased antiviral activity of cyclic urea HIV protease inhibitors by modifying the P1/P1′ substituents
  作者：Robert F. Kaltenbach、Ronald M. Klabe、Beverly C. Cordova、Steven P. Seitz

  DOI：10.1016/s0960-894x(99)00367-4

  日期：1999.8

  A series of alkyl substituted P1/P1' analogs was prepared in an attempt to increase translation of the 3-aminoindazole class of HIV protease inhibitors. Increasing the lipophilicity of the P1/P1' residues dramatically improved translation of enzyme activity to antiviral activity in the whole cell assay. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.