N-((1S,2R)-1-Benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-methoxybenzamide

• 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-((1S,2R)-1-Benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-methoxybenzamide
• 英文别名: N-[(2S,3R)-3-hydroxy-4-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]-2-methoxybenzamide
• 化学式: C₂₉H₃₆N₂O₆S
• 分子量: 540.681
• InChiKey: GGEKVPJEZSCVNJ-RRPNLBNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  Phenylmethyl [2R-hydroxy-3-[(2-methylpropyl)(4-methoxyphenylsulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate 在 palladium on activated charcoal 氢气 作用下， 生成 N-((1S,2R)-1-Benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-methoxybenzamide
  参考文献：
  名称：

  (Hydroxyethyl) sulfonamide HIV-1 Protease inhibitors: Identification of the 2-methylbenzoyl moiety at P-2

  摘要：

  We have discovered a potent low molecular weight series of HIV-1 Protease inhibitors incorporating the (R)-(hydroxyethyl) sulfonamide isostere.

  DOI：

  10.1016/0960-894x(96)00035-2

文献信息

• Model System for High-Throughput Screening of Novel Human Immunodeficiency Virus Protease Inhibitors in <i>Escherichia coli</i>
  作者：Ting-Jen Cheng、Ashraf Brik、Chi-Huey Wong、Chen-Chen Kan

  DOI：10.1128/aac.48.7.2437-2447.2004

  日期：2004.7

  Novel human immunodeficiency virus (HIV) protease inhibitors are urgently needed for combating the drug-resistance problem in the fight against AIDS. To facilitate lead discovery of HIV protease inhibitors, we have developed a safe, convenient, and cost-effective Escherichia coli -based assay system. This E. coli -based system involves coexpression of an engineered β-galactosidase as an HIV protease substrate and the HIV protease precursor comprising the transframe region and the protease domain. Autoprocessing of the HIV protease precursor releases the mature HIV protease. Subsequently, the HIV protease cleaves β-galactosidase, resulting in a loss of the β-galactosidase activity, which can be detected in high-throughput screens. Using Food and Drug Administration-approved HIV protease inhibitors, this E. coli -based system is validated as a surrogate screening system for identifying inhibitors that not only possess inhibitory activity against HIV protease but also have solubility and permeability for in vivo activity. The usefulness of the E. coli -based system was demonstrated with the identification of a novel HIV protease inhibitor from a library of compounds that were prepared by an amide-forming reaction with transition-state analog cores. A novel inhibitor with a sulfonamide core of amprenavir, E2, has shown good correlation with the in vitro enzymatic assay and in vivo E. coli -based system. This system can also be used to generate drug resistance profiles that could be used to suggest therapeutic uses of HIV protease inhibitors to treat the drug-resistant HIV strains. This simple yet efficient E. coli system not only represents a screening platform for high-throughput identification of leads targeting the HIV proteases but also can be adapted to all other classes of proteases.

  摘要 在抗击艾滋病的过程中，迫切需要新型人类免疫缺陷病毒（HIV）蛋白酶抑制剂来解决耐药性问题。为了促进 HIV 蛋白酶抑制剂的先导发现，我们开发了一种安全、方便且经济有效的 基于大肠杆菌 -检测系统。这种 大肠杆菌 -基于大肠杆菌的这一系统包括共同表达作为 HIV 蛋白酶底物的工程化 β-半乳糖苷酶和由转框区和蛋白酶结构域组成的 HIV 蛋白酶前体。艾滋病毒蛋白酶前体的自动处理会释放出成熟的艾滋病毒蛋白酶。随后，HIV蛋白酶会裂解β-半乳糖苷酶，导致β-半乳糖苷酶活性丧失，这可在高通量筛选中检测到。利用食品与药物管理局批准的艾滋病毒蛋白酶抑制剂，该 大肠杆菌 -系统被验证为一种替代筛选系统，可用于鉴定不仅对 HIV 蛋白酶具有抑制活性，而且具有溶解性和渗透性的体内活性抑制剂。大肠杆菌 大肠杆菌 -通过与过渡态类似物核心进行酰胺化反应制备的化合物库中鉴定出一种新型 HIV 蛋白酶抑制剂，证明了基于大肠杆菌的系统的实用性。一种以安非那韦为磺酰胺核心的新型抑制剂 E2 与体外酶测定和体内 大肠杆菌 -系统有很好的相关性。该系统还可用于生成耐药性图谱，从而建议使用艾滋病毒蛋白酶抑制剂治疗耐药艾滋病毒菌株。这种简单而高效的 大肠杆菌 系统不仅是高通量鉴定针对 HIV 蛋白酶的新药的筛选平台，还可用于所有其他类别的蛋白酶。
• (Hydroxyethyl) sulfonamide HIV-1 Protease inhibitors: Identification of the 2-methylbenzoyl moiety at P-2
  作者：John N. Freskos、Deborah E. Bertenshaw、Daniel P. Getman、Robert M. Heintz、Brent V. Mischke、Lisa W. Blystone、Martin L. Bryant、Christine Funckes-Shippy、Kathyrn A. Houseman、Nandini N. Kishore、Geralyn P. Kocan、Pramod P. Mehta

  DOI：10.1016/0960-894x(96)00035-2

  日期：1996.2

  We have discovered a potent low molecular weight series of HIV-1 Protease inhibitors incorporating the (R)-(hydroxyethyl) sulfonamide isostere.