N-[(1S,2R)-3-[1,3-benzothiazol-6-ylsulfonyl-[(2S)-2-methylbutyl]amino]-1-benzyl-2-hydroxy-propyl]-3-fluoro-2-methyl-benzamide | 1066865-55-1

• 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)-3-[1,3-benzothiazol-6-ylsulfonyl-[(2S)-2-methylbutyl]amino]-1-benzyl-2-hydroxy-propyl]-3-fluoro-2-methyl-benzamide
• 英文别名: N-[(2S,3R)-4-[1,3-benzothiazol-6-ylsulfonyl-[(2S)-2-methylbutyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-3-fluoro-2-methylbenzamide
• CAS: 1066865-55-1
• 化学式: C₃₀H₃₄FN₃O₄S₂
• 分子量: 583.748
• InChiKey: WJIQPYQTWBEMJG-XNZIZSAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-((S)-2-methylbutyl)benzo[d]thiazole-6-sulfonamide 、 3-氟-2-甲基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 为溶剂， 以82%的产率得到N-[(1S,2R)-3-[1,3-benzothiazol-6-ylsulfonyl-[(2S)-2-methylbutyl]amino]-1-benzyl-2-hydroxy-propyl]-3-fluoro-2-methyl-benzamide
  参考文献：
  名称：

  Additivity in the Analysis and Design of HIV Protease Inhibitors

  摘要：

  We explore the applicability of an additive treatment of substituent effects to the analysis and design of HIV protease inhibitors. Affinity data for a set of inhibitors with a common chemical framework were analyzed to provide estimates of the free energy contribution of each chemical substituent. These estimates were then used to design new inhibitors whose high affinities were confirmed by synthesis and experimental testing. Derivations of additive models by least-squares and ridge-regression methods were found to yield statistically similar results. The additivity approach was also compared with standard molecular descriptor-based QSAR; the latter was not found to provide superior predictions. Crystallographic studies of HIV protease-inhibitor complexes help explain the perhaps surprisingly high degree of substituent additivity in this system, and allow some of the additivity coefficients to be rationalized on a structural basis.

  DOI：

  10.1021/jm8009525

文献信息

• HIV-1 Protease Inhibitors
  申请人：Ali Akbar

  公开号：US20110178092A1

  公开（公告）日：2011-07-21

  Described are novel protease inhibitors and methods for using said protease inhibitors in the treatment of human immunodeficiency virus (HIV) infection.
• Additivity in the Analysis and Design of HIV Protease Inhibitors
  作者：Robert N. Jorissen、G. S. Kiran Kumar Reddy、Akbar Ali、Michael D. Altman、Sripriya Chellappan、Saima G. Anjum、Bruce Tidor、Celia A. Schiffer、Tariq M. Rana、Michael K. Gilson

  DOI：10.1021/jm8009525

  日期：2009.2.12

  We explore the applicability of an additive treatment of substituent effects to the analysis and design of HIV protease inhibitors. Affinity data for a set of inhibitors with a common chemical framework were analyzed to provide estimates of the free energy contribution of each chemical substituent. These estimates were then used to design new inhibitors whose high affinities were confirmed by synthesis and experimental testing. Derivations of additive models by least-squares and ridge-regression methods were found to yield statistically similar results. The additivity approach was also compared with standard molecular descriptor-based QSAR; the latter was not found to provide superior predictions. Crystallographic studies of HIV protease-inhibitor complexes help explain the perhaps surprisingly high degree of substituent additivity in this system, and allow some of the additivity coefficients to be rationalized on a structural basis.