(4S)-N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide | 603141-83-9

• 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: (4S)-N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide
• 英文别名: (2S,4S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-N-(1-cyanocyclopropyl)-5,5,5-trifluoro-4-methylpentanamide
• CAS: 603141-83-9
• 化学式: C₁₈H₁₈BrF₆N₃O
• 分子量: 486.255
• InChiKey: QKVVXZCYXDQLKN-BPNCWPANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.9
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (4S)-N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide 、 4-甲硫基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (4S)-N¹-(1-cyanocyclopropyl)-5,5,5-trifluoro-N²-{(1S)-2,2,2-trifluoro-1-[4'-(methylthio)-1,1'-biphenyl-4-yl]ethyl}-L-leucinamide
  参考文献：
  名称：

  The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K

  摘要：

  Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.047
• 作为产物：
  描述：

  (4S)-N-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-5,5,5-trifluoro-L-leucine 、 1-氨基-1-环丙基腈盐酸盐 在 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 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (4S)-N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide
  参考文献：
  名称：

  The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K

  摘要：

  Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.047

文献信息

• Cathepsin cysteine protease inhibitors
  申请人：——

  公开号：US20030232863A1

  公开（公告）日：2003-12-18

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类新型化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• CATHEPSIN CYSTEINE PROTEASE INHIBIORS
  申请人：Merck, Sharp & Dohme, Corp.

  公开号：US20130035312A1

  公开（公告）日：2013-02-07

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  本发明涉及一种新型化合物类别，它们是半胱氨酸蛋白酶抑制剂，包括但不限于，猫hepsins K，L，S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1482924B1

  公开（公告）日：2008-05-21
• US20140256743A1
  申请人：——

  公开号：US20140256743A1

  公开（公告）日：2014-09-11
• US7375134B2
  申请人：——

  公开号：US7375134B2

  公开（公告）日：2008-05-20