N-[(3S,4S)-4-[benzenesulfonyl-[(4-bromophenyl)methyl]amino]pyrrolidin-3-yl]-N-[(4-bromophenyl)methyl]benzenesulfonamide;hydrochloride | 1020573-26-5

• 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: N-[(3S,4S)-4-[benzenesulfonyl-[(4-bromophenyl)methyl]amino]pyrrolidin-3-yl]-N-[(4-bromophenyl)methyl]benzenesulfonamide;hydrochloride
• CAS: 1020573-26-5
• 化学式: C₃₀H₂₉Br₂N₃O₄S₂*ClH
• 分子量: 755.979
• InChiKey: YHMKUNLYACKUJI-PNHSAAKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.06
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (3S,4S)-1-tert-butoxycarbonyl-3,4-bis[benzenesulfonyl-(4-bromo-benzyl)-amino]-pyrrolidine 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 14.0h， 以72%的产率得到N-[(3S,4S)-4-[benzenesulfonyl-[(4-bromophenyl)methyl]amino]pyrrolidin-3-yl]-N-[(4-bromophenyl)methyl]benzenesulfonamide;hydrochloride
  参考文献：
  名称：

  Structure-Guided Design of C₂-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold

  摘要：

  Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis-N-alkylsulfonamides were designed and synthesized enantioselectively from D-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K(i) = 74 nM.

  DOI：

  10.1021/jm701142s

文献信息

• Structure-Guided Design of <i>C</i>₂-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold
  作者：Andreas Blum、Jark Böttcher、Andreas Heine、Gerhard Klebe、Wibke E. Diederich

  DOI：10.1021/jm701142s

  日期：2008.4.1

  Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis-N-alkylsulfonamides were designed and synthesized enantioselectively from D-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K(i) = 74 nM.