N-(4-benzyloxycarbonylamidino-benzyl)-2-[(S)-4-(2,3-dihydro-benzofuran-5-sulfonylamino)-3-oxo-morpholin-2-yl]-acetamide acid benzyl ester | 609846-97-1

• 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-(4-benzyloxycarbonylamidino-benzyl)-2-[(S)-4-(2,3-dihydro-benzofuran-5-sulfonylamino)-3-oxo-morpholin-2-yl]-acetamide acid benzyl ester
• 英文别名: benzyl (NZ)-N-[amino-[4-[[[2-[(2S)-4-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-3-oxomorpholin-2-yl]acetyl]amino]methyl]phenyl]methylidene]carbamate
• CAS: 609846-97-1
• 化学式: C₃₀H₃₁N₅O₈S
• 分子量: 621.671
• InChiKey: RCTZGBMGEBFGON-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  187
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(4-benzyloxycarbonylamidino-benzyl)-2-[(S)-4-(2,3-dihydro-benzofuran-5-sulfonylamino)-3-oxo-morpholin-2-yl]-acetamide acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 1.0h， 生成 N-(4-Carbamimidoyl-benzyl)-2-[(S)-4-(2,3-dihydro-benzofuran-5-sulfonylamino)-3-oxo-morpholin-2-yl]-acetamide
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990
• 作为产物：
  描述：

  (S)-2-(2-oxo-ethoxy)-succinic acid dimethyl ester 在 palladium on activated charcoal 吡啶 、 lithium hydroxide 、 水 、 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.17h， 生成 N-(4-benzyloxycarbonylamidino-benzyl)-2-[(S)-4-(2,3-dihydro-benzofuran-5-sulfonylamino)-3-oxo-morpholin-2-yl]-acetamide acid benzyl ester
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990