N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide | 603142-77-4

• 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: N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide
• 英文别名: N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N1-(1-cyanocyclopropyl)-4,4-difluoro-1-norvalinamide；(2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-N-(1-cyanocyclopropyl)-4,4-difluoropentanamide
• CAS: 603142-77-4
• 化学式: C₁₇H₁₇BrF₅N₃O
• 分子量: 454.237
• InChiKey: NMIBJCZFHFGHBJ-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  64.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide 、 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 N¹-(1-cyanocyclopropyl)-4,4-difluoro-N²-{(1S)-2,2,2-trifluoro-1-[4'-(methylthio)-1,1'-biphenyl-4-yl]ethyl}-L-norvalinamide
  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：

  N-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-4,4-difluoro-L-norvaline 、 1-氨基-1-环丙基腈盐酸盐 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 48.0h， 生成 N²-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide
  参考文献：
  名称：

  [EN] CATHEPSIN INHIBITORS
  [FR] INHIBITEURS DE LA CATHEPSINE

  摘要：

  这项发明涉及一类新型化合物，由下式（I）表示，其中R1、R2、R3和R4的含义已在其中指示，这些化合物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。这些化合物对于治疗需要抑制骨吸收的疾病非常有用，如骨质疏松症、骨关节炎和类风湿性关节炎。

  公开号：

  WO2005021487A1

文献信息

• [EN] CATHEPSIN INHIBITORS<br/>[FR] INHIBITEURS DE LA CATHEPSINE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2005021487A1

  公开（公告）日：2005-03-10

  This invention relates to a novel class of compounds, represented by the formula (I) below, wherein the meanings of R1, R2, R3 and R4 are indicated therein, 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, osteoarthritis and rheumatoid arthritis.

  这项发明涉及一类新型化合物，由下式（I）表示，其中R1、R2、R3和R4的含义已在其中指示，这些化合物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。这些化合物对于治疗需要抑制骨吸收的疾病非常有用，如骨质疏松症、骨关节炎和类风湿性关节炎。
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1482924B1

  公开（公告）日：2008-05-21
• The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
  作者：Jacques Yves Gauthier、Nathalie Chauret、Wanda Cromlish、Sylvie Desmarais、Le T. Duong、Jean-Pierre Falgueyret、Donald B. Kimmel、Sonia Lamontagne、Serge Léger、Tammy LeRiche、Chun Sing Li、Frédéric Massé、Daniel J. McKay、Deborah A. Nicoll-Griffith、Renata M. Oballa、James T. Palmer、M. David Percival、Denis Riendeau、Joel Robichaud、Gideon A. Rodan、Sevgi B. Rodan、Carmai Seto、Michel Thérien、Vouy-Linh Truong、Michael C. Venuti、Gregg Wesolowski、Robert N. Young、Robert Zamboni、W. Cameron Black

  DOI：10.1016/j.bmcl.2007.12.047

  日期：2008.2

  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.