benzylsulfonyl-D-cyclohexylalanyl-proline-(2-aminomethyl-5-chlorobenzyl)amide | 1239703-96-8

• 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: benzylsulfonyl-D-cyclohexylalanyl-proline-(2-aminomethyl-5-chlorobenzyl)amide
• 英文别名: N-(Benzylsulfonyl)-3-Cyclohexyl-D-Alanyl-N-[2-(Aminomethyl)-5-Chlorobenzyl]-L-Prolinamide；(2S)-N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-1-[(2R)-2-(benzylsulfonylamino)-3-cyclohexylpropanoyl]pyrrolidine-2-carboxamide
• CAS: 1239703-96-8
• 化学式: C₂₉H₃₉ClN₄O₄S
• 分子量: 575.172
• InChiKey: SMGIPPNIBFQJBW-SXOMAYOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzylsulfonyl-D-cyclohexylalanyl-proline-(2-aminomethyl-5-chlorobenzyl)amide 、 三氟乙酸 反应 1.5h， 以0.24 g的产率得到benzylsulfonyl-D-cyclohexylalanyl-proline-(2-aminomethyl-5-chlorobenzyl)amide trifluoroacetate
  参考文献：
  名称：

  Identification of the First Low-Molecular-Weight Inhibitors of Matriptase-2

  摘要：

  As recently discovered, matriptase-2, a type II transmembrane serine protease, plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels. Thus, matriptase-2 represents a novel target for the development of enzyme inhibitors potentially useful for the treatment of systemic iron overload (hemochromatosis). A comparative three-dimensional model of the catalytic domain of matriptase-2 was generated and utilized for structure-based virtual screening in combination with similarity searching and knowledge-based compound design. Two N-protected dipeptide amides containing a 4-amidinobenzylamide as PI residue (compounds 1 and 3) were identified as the first small molecule inhibitors of matriptase-2 with K-i values of 170 and 460 nM, respectively. An inhibitor of the closely related protease matriptase (compound 2, K-i = 220 nM), with more than 50-fold selectivity over matriptase-2, was also identified.

  DOI：

  10.1021/jm100183e
• 作为产物：
  描述：

  N-benzylsulfonyl-D-(β-cyclohexyl)alanyl-L-proline 、 2-(氨基甲基)-4-氯苄基氨基甲酸叔丁酯 在 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 4.25h， 生成 benzylsulfonyl-D-cyclohexylalanyl-proline-(2-aminomethyl-5-chlorobenzyl)amide
  参考文献：
  名称：

  Identification of the First Low-Molecular-Weight Inhibitors of Matriptase-2

  摘要：

  As recently discovered, matriptase-2, a type II transmembrane serine protease, plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels. Thus, matriptase-2 represents a novel target for the development of enzyme inhibitors potentially useful for the treatment of systemic iron overload (hemochromatosis). A comparative three-dimensional model of the catalytic domain of matriptase-2 was generated and utilized for structure-based virtual screening in combination with similarity searching and knowledge-based compound design. Two N-protected dipeptide amides containing a 4-amidinobenzylamide as PI residue (compounds 1 and 3) were identified as the first small molecule inhibitors of matriptase-2 with K-i values of 170 and 460 nM, respectively. An inhibitor of the closely related protease matriptase (compound 2, K-i = 220 nM), with more than 50-fold selectivity over matriptase-2, was also identified.

  DOI：

  10.1021/jm100183e