(S)-2-((S)-2-(3-chlorophenyl)-2-methylsulfonamidoacetamido)-N-(2-((cyanomethyl)amino)-2-oxoethyl)-3-phenylpropanamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-((S)-2-(3-chlorophenyl)-2-methylsulfonamidoacetamido)-N-(2-((cyanomethyl)amino)-2-oxoethyl)-3-phenylpropanamide
• 英文别名: (2S)-2-[[(2S)-2-(3-chlorophenyl)-2-(methanesulfonamido)acetyl]amino]-N-[2-(cyanomethylamino)-2-oxoethyl]-3-phenylpropanamide
• 化学式: C₂₂H₂₄ClN₅O₅S
• 分子量: 505.982
• InChiKey: OWKQZWZENLZUDI-ICSRJNTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  BOC-L-苯丙氨酸琥珀酰亚胺酯 在 N-甲基吗啉 、 甲酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 (S)-2-((S)-2-(3-chlorophenyl)-2-methylsulfonamidoacetamido)-N-(2-((cyanomethyl)amino)-2-oxoethyl)-3-phenylpropanamide
  参考文献：
  名称：

  Discovery and Structure-Based Optimization of Adenain Inhibitors

  摘要：

  The cysteine protease adenain is the essential protease of adenovirus and, as such, represents a promising target for the treatment of ocular and other adenoviral infections. Through a concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 and pyrimidine nitrile 2 as complementary starting points for adenain inhibition. These hits enabled the first high-resolution X-ray cocrystal structures of adenain with inhibitors bound and revealed the binding mode of 1 and 2. The screening hits were optimized by a structure-guided medicinal chemistry strategy into low nanomolar drug-like inhibitors of adenain.

  DOI：

  10.1021/ml500224t

文献信息

• Discovery and Structure-Based Optimization of Adenain Inhibitors
  作者：Aengus Mac Sweeney、Philipp Grosche、David Ellis、Keith Combrink、Paul Erbel、Nicola Hughes、Finton Sirockin、Samu Melkko、Anna Bernardi、Paul Ramage、Nadine Jarousse、Eva Altmann

  DOI：10.1021/ml500224t

  日期：2014.8.14

  The cysteine protease adenain is the essential protease of adenovirus and, as such, represents a promising target for the treatment of ocular and other adenoviral infections. Through a concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 and pyrimidine nitrile 2 as complementary starting points for adenain inhibition. These hits enabled the first high-resolution X-ray cocrystal structures of adenain with inhibitors bound and revealed the binding mode of 1 and 2. The screening hits were optimized by a structure-guided medicinal chemistry strategy into low nanomolar drug-like inhibitors of adenain.