methyl (S)-2-((S)-3-(4-(benzyloxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate | 1036717-95-9

• 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: methyl (S)-2-((S)-3-(4-(benzyloxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• CAS: 1036717-95-9
• 化学式: C₃₂H₃₆N₂O₆
• 分子量: 544.648
• InChiKey: JERWBJLLHYJNSN-NSOVKSMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  94.17
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-((S)-3-(4-(benzyloxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 sodium hydroxide 、 水 、 potassium hydrogensulfate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以93%的产率得到(3S)-N-(Boc-L-tyrosinyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  (3S)-N-(l-Aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic agents: Synthesis, bioassay, 3D QSAR, and ADME analysis

  摘要：

  To increase antithrombotic activity, 3S-tetrahydroisoquinoline-3-carboxylic acid (1) was modified with natural amino acids to form 19 novel dipeptide analogs, 3S-tetrahydroisoquinoline-3-carboxyamino acids (5a-s), targeting the intestinal peptide transport system. In vitro assay of 5a-s indicated that their potencies for inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH)-induced platelet aggregations were higher than that of 1. Additionally, in vivo assay of 5a-s indicated that their potencies for inhibiting thrombogenesis in rats were also higher than that of 1. Among the candidates, 5h with Ser attachment showed the most impressive features for further development. According to molecular field analysis based Cerius(2) QSAR module, two equations (r, 0.961 and 0.988) correlating the structures with both in vitro and in vivo activities of 5a-s were established. ADMET calculations predict higher intestinal absorption for compounds 5a-s. Further investigation with 5h as a lead compound is underway. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.019
• 作为产物：
  描述：

  Boc-L-Tyr(Bzl)-OBt 、 methyl (3S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 14.5h， 以82%的产率得到methyl (S)-2-((S)-3-(4-(benzyloxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  (3S)-N-(l-Aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic agents: Synthesis, bioassay, 3D QSAR, and ADME analysis

  摘要：

  To increase antithrombotic activity, 3S-tetrahydroisoquinoline-3-carboxylic acid (1) was modified with natural amino acids to form 19 novel dipeptide analogs, 3S-tetrahydroisoquinoline-3-carboxyamino acids (5a-s), targeting the intestinal peptide transport system. In vitro assay of 5a-s indicated that their potencies for inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH)-induced platelet aggregations were higher than that of 1. Additionally, in vivo assay of 5a-s indicated that their potencies for inhibiting thrombogenesis in rats were also higher than that of 1. Among the candidates, 5h with Ser attachment showed the most impressive features for further development. According to molecular field analysis based Cerius(2) QSAR module, two equations (r, 0.961 and 0.988) correlating the structures with both in vitro and in vivo activities of 5a-s were established. ADMET calculations predict higher intestinal absorption for compounds 5a-s. Further investigation with 5h as a lead compound is underway. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.019