(4S,5S)-2,7-bis(2-bromobenzyl)-4,5-O-isopropylidene-1,2,7-thiadiazepine 1,1-dioxide | 891143-61-6

• 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: (4S,5S)-2,7-bis(2-bromobenzyl)-4,5-O-isopropylidene-1,2,7-thiadiazepine 1,1-dioxide
• 英文别名: (3aS,8aS)-5,7-bis[(2-bromophenyl)methyl]-2,2-dimethyl-3a,4,8,8a-tetrahydro-[1,3]dioxolo[4,5-d][1,2,7]thiadiazepine 6,6-dioxide
• CAS: 891143-61-6
• 化学式: C₂₁H₂₄Br₂N₂O₄S
• 分子量: 560.307
• InChiKey: PDESPHWNVWIPKV-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  67.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,5S)-2,7-bis(2-bromobenzyl)-4,5-O-isopropylidene-1,2,7-thiadiazepine 1,1-dioxide 在 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 盐酸 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 乙醚 为溶剂， 反应 1.0h， 生成 (4S,5S)-3,4,5,6-tetrahydro-2,7-bis{2-[2-(3-methoxy-phenyl)-acetamido]-benzyl}-4,5-dihydroxy-1,2,7-thiadiazepine 1,1-dioxide
  参考文献：
  名称：

  Fast and selective synthesis of novel cyclic sulfamide HIV-1 protease inhibitors under controlled microwave heating

  摘要：

  A novel and highly selective silver-promoted monobenzylation method was developed to promote synthesis of nonsymmetrical sulfamide-based HIV-1 inhibitors. Microwave-accelerated palladium-catalyzed N-amide arylation- and aminocarbonylation reactions were employed for rapid and reliable compound generation. With this class of inhibitory agents, six active inhibitors were identified, the most potent inhibitor possessing a K-i-value of 20 nM. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.11.094
• 作为产物：
  描述：

  (4S,5S)-4,5-二(氨甲基)-2,2-二甲基二氧杂烷 在 potassium carbonate 、 磺酰胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 (4S,5S)-2,7-bis(2-bromobenzyl)-4,5-O-isopropylidene-1,2,7-thiadiazepine 1,1-dioxide
  参考文献：
  名称：

  Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2′ to P1/P1′

  摘要：

  Previous studies of HIV protease inhibitors have shown that it is possible to elongate the P1/P1' sidechains to reach the S3/S3' binding sites. By analogy, We expected that it would be possible to design inhibitors reaching between the S1/S1' and S2/S2' binding sites. Molecular modeling suggested that this could be achieved with appropriate ortho-substitution of the P2/P2' benzyl groups in our cyclic sulfamide inhibitors. Four different spacer groups were investigated. The compounds were smoothly prepared 44 from tartaric acid in five steps and exhibit low to moderate activity, the most potent inhibitor possessing a K-i value of 0.53 muM. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.042

文献信息

• Synthesis of a small library of non-symmetric cyclic sulfamide HIV-1 protease inhibitors
  作者：Anna Ax、Advait A. Joshi、Kristina M. Orrling、Lotta Vrang、Bertil Samuelsson、Anders Hallberg、Anders Karlén、Mats Larhed

  DOI：10.1016/j.tet.2010.04.023

  日期：2010.6

  A set of 11 non-symmetric cyclic sulfamide HIV-1 protease inhibitors were synthesized and evaluated. The use of a key microwave-assisted silver(I) oxide mediated selective mono N-benzylation reaction enabled fast and straightforward synthesis. The Ki values of the new inhibitors ranged between 0.28 μM and >20 μM.

  合成并评估了一组11种非对称环硫酰胺HIV-1蛋白酶抑制剂。使用关键的微波辅助氧化银（I）介导的选择性单N-苄基化反应可实现快速直接的合成。新抑制剂的K i值介于0.28μM和> 20μM之间。
• Fast and selective synthesis of novel cyclic sulfamide HIV-1 protease inhibitors under controlled microwave heating
  作者：Henrik Gold、Anna Ax、Lotta Vrang、Bertil Samuelsson、Anders Karlén、Anders Hallberg、Mats Larhed

  DOI：10.1016/j.tet.2005.11.094

  日期：2006.5

  A novel and highly selective silver-promoted monobenzylation method was developed to promote synthesis of nonsymmetrical sulfamide-based HIV-1 inhibitors. Microwave-accelerated palladium-catalyzed N-amide arylation- and aminocarbonylation reactions were employed for rapid and reliable compound generation. With this class of inhibitory agents, six active inhibitors were identified, the most potent inhibitor possessing a K-i-value of 20 nM. (c) 2006 Elsevier Ltd. All rights reserved.
• Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2′ to P1/P1′
  作者：Anna Ax、Wesley Schaal、Lotta Vrang、Bertil Samuelsson、Anders Hallberg、Anders Karlén

  DOI：10.1016/j.bmc.2004.10.042

  日期：2005.2

  Previous studies of HIV protease inhibitors have shown that it is possible to elongate the P1/P1' sidechains to reach the S3/S3' binding sites. By analogy, We expected that it would be possible to design inhibitors reaching between the S1/S1' and S2/S2' binding sites. Molecular modeling suggested that this could be achieved with appropriate ortho-substitution of the P2/P2' benzyl groups in our cyclic sulfamide inhibitors. Four different spacer groups were investigated. The compounds were smoothly prepared 44 from tartaric acid in five steps and exhibit low to moderate activity, the most potent inhibitor possessing a K-i value of 0.53 muM. (C) 2004 Elsevier Ltd. All rights reserved.