(S)-2-[({(3R,4aS,8aR)-2-[(1,1'-biphenyl)-4-carbonyl]decahydroisoquinolin-3-yl}methyl)amino]-3-(1H-imidazol-4-yl)propanal

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (S)-2-[({(3R,4aS,8aR)-2-[(1,1'-biphenyl)-4-carbonyl]decahydroisoquinolin-3-yl}methyl)amino]-3-(1H-imidazol-4-yl)propanal
• 英文别名: (2s)-2-({[(3r,4as,8ar)-2-(Biphenyl-4-Ylcarbonyl)decahydroisoquinolin-3-Yl]methyl}amino)-3-(1h-Imidazol-5-Yl)propanal；(2S)-2-[[(3R,4aS,8aR)-2-(4-phenylbenzoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-3-yl]methylamino]-3-(1H-imidazol-5-yl)propanal
• 化学式: C₂₉H₃₄N₄O₂
• 分子量: 470.615
• InChiKey: VZCULZJNALRGNB-DNZWLJDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-4-[(1R/S,2S/R)-2-{[(tert-butyldiphenylsilyl)oxy]-methyl}cyclohexyl]but-2-en-1-ol 在 吡啶 、 4-二甲氨基吡啶 、 potassium osmate 、 双(乙腈)氯化钯(II) 、 lithium aluminium tetrahydride 、 三异丙基硅烷 、 叠氮磷酸二苯酯 、 四丁基氟化铵 、 二异丁基氢化铝 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 55.08h， 生成 (S)-2-[({(3R,4aS,8aR)-2-[(1,1'-biphenyl)-4-carbonyl]decahydroisoquinolin-3-yl}methyl)amino]-3-(1H-imidazol-4-yl)propanal
  参考文献：
  名称：

  Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors

  摘要：

  The design and evaluation of a novel decahydroisoquinolin scaffold as an inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL(pro)) are described. Focusing on hydrophobic interactions at the S-2 site, the decahydroisoquinolin scaffold was designed by connecting the P-2 site cyclohexyl group of the substrate-based inhibitor to the main-chain at the alpha-nitrogen atom of the P-2 position via a methylene linker. Starting from a cyclohexene enantiomer obtained by salt resolution, trans-decahydroisoquinolin derivatives were synthesized. All decahydroisoquinolin inhibitors synthesized showed moderate but clear inhibitory activities for SARS 3CL(pro), which confirmed the fused ring structure of the decahydroisoquinolin functions as a novel scaffold for SARS 3CL(pro) inhibitor. X-ray crystallographic analyses of the SARS 3CL(pro) in a complex with the decahydroisoquinolin inhibitor revealed the expected interactions at the S-1 and S-2 sites, as well as additional interactions at the N-substituent of the inhibitor. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.028