(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-[4-(1-hydroxycyclopropyl)phenyl]phenyl]ethyl]amino]pentanamide | 1217864-21-5

• 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: (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-[4-(1-hydroxycyclopropyl)phenyl]phenyl]ethyl]amino]pentanamide
• CAS: 1217864-21-5
• 化学式: C₂₇H₂₉F₄N₃O₂
• 分子量: 503.54
• InChiKey: DUNBFDMCPKOBRW-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-(((S)-2,2,2-trifluoro-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)amino)pentanamide 、 [1-(4-bromophenyl)cyclopropoxy](tert-butyl)dimethylsilane 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 氟化氢吡啶 作用下， 生成 (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-[4-(1-hydroxycyclopropyl)phenyl]phenyl]ethyl]amino]pentanamide
  参考文献：
  名称：

  The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor

  摘要：

  MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency pro. le against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.12.083

文献信息

• The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor
  作者：Elise Isabel、Kevin P. Bateman、Nathalie Chauret、Wanda Cromlish、Sylvie Desmarais、Le T. Duong、Jean-Pierre Falgueyret、Jacques Yves Gauthier、Sonia Lamontagne、Cheuk K. Lau、Serge Léger、Tammy LeRiche、Jean-François Lévesque、Chun Sing Li、Frédéric Massé、Daniel J. McKay、Christophe Mellon、Deborah A. Nicoll-Griffith、Renata M. Oballa、M. David Percival、Denis Riendeau、Joël Robichaud、Gideon A. Rodan、Sevgi B. Rodan、Carmai Seto、Michel Thérien、Vouy Linh Truong、Gregg Wesolowski、Robert N. Young、Robert Zamboni、W. Cameron Black

  DOI：10.1016/j.bmcl.2009.12.083

  日期：2010.2

  MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency pro. le against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards. (C) 2009 Published by Elsevier Ltd.