(S)-methyl 3-methyl-5-((1-phenylbut-3-yn-1-yl)carbamoyl)benzoate | 1385068-73-4

• 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: (S)-methyl 3-methyl-5-((1-phenylbut-3-yn-1-yl)carbamoyl)benzoate
• CAS: 1385068-73-4
• 化学式: C₂₀H₁₉NO₃
• 分子量: 321.376
• InChiKey: QVJAKDQSKLZXQC-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-methyl 3-methyl-5-((1-phenylbut-3-yn-1-yl)carbamoyl)benzoate 在 喹啉 、 Hoveyda-Grubbs catalyst second generation 、 氢气 、 二正丁基氧化锡 、 溶剂黄146 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0~60.0 ℃ 、101.33 kPa 条件下， 反应 67.42h， 生成 (E)-(4S,11S)-4-[(R)-1-hydroxy-2-(3-isopropyl-benzylamino)-ethyl]-16-methyl-11-phenyl-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraene-2,13-dione
  参考文献：
  名称：

  Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes

  摘要：

  A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC50 values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.039
• 作为产物：
  描述：

  (S)-环氧苯乙烷 在 1,3-丙二硫醇 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 偶氮二甲酸二异丙酯 、 叠氮磷酸二苯酯 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 101.0h， 生成 (S)-methyl 3-methyl-5-((1-phenylbut-3-yn-1-yl)carbamoyl)benzoate
  参考文献：
  名称：

  Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes

  摘要：

  A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC50 values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.039