darunavir | 1066867-56-8

• 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: darunavir
• 英文别名: (3r,3as,6ar)-Hexahydrofuro[2,3-B]furan-3-Yl {(1s,2r)-3-[(1,3-Benzothiazol-6-Ylsulfonyl)(2-Ethylbutyl)amino]-1-Benzyl-2-Hydroxypropyl}carbamate；[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-4-[1,3-benzothiazol-6-ylsulfonyl(2-ethylbutyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 1066867-56-8
• 化学式: C₃₀H₃₉N₃O₇S₂
• 分子量: 617.788
• InChiKey: RAFDIRILGICCDS-OPUPNEDUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  164
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-乙基丁胺 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 28.0h， 生成 darunavir
  参考文献：
  名称：

  Substrate Envelope-Designed Potent HIV-1 Protease Inhibitors to Avoid Drug Resistance

  摘要：

  The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (Pis) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed Pis share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed Pis retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.

  DOI：

  10.1016/j.chembiol.2013.07.014

文献信息

• Substrate Envelope-Designed Potent HIV-1 Protease Inhibitors to Avoid Drug Resistance
  作者：Madhavi N.L. Nalam、Akbar Ali、G.S. Kiran Kumar Reddy、Hong Cao、Saima G. Anjum、Michael D. Altman、Nese Kurt Yilmaz、Bruce Tidor、Tariq M. Rana、Celia A. Schiffer

  DOI：10.1016/j.chembiol.2013.07.014

  日期：2013.9

  The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (Pis) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed Pis share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed Pis retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.