(S)-2-{(R)-2,2-Dimethyl-1-[5-(4-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propoxycarbonylamino}-hexanoic acid methyl ester | 497947-14-5

• 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: (S)-2-{(R)-2,2-Dimethyl-1-[5-(4-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propoxycarbonylamino}-hexanoic acid methyl ester
• 英文别名: methyl (2S)-2-[({[(1R)-2,2-dimethyl-1-({5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}methyl)propyl]oxy}carbonyl)amino]hexanoate；methyl (2S)-2-[[(2R)-3,3-dimethyl-1-[5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]butan-2-yl]oxycarbonylamino]hexanoate
• CAS: 497947-14-5
• 化学式: C₂₃H₃₀F₃N₃O₅
• 分子量: 485.504
• InChiKey: XWXVXSMUNRRQFC-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-2-{(R)-2,2-Dimethyl-1-[5-(4-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propoxycarbonylamino}-hexanoic acid methyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide 、 臭氧 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (1R)-2,2-Dimethyl-1-({5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-YL}methyl)propyl (1S)-1-{oxo[(2-oxo-1,3-oxazolidin-3-YL)amino]acetyl}pentylcarbamate
  参考文献：
  名称：

  P2–P3 conformationally constrained ketoamide-based inhibitors of cathepsin K

  摘要：

  An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.

  DOI：

  10.1016/j.bmcl.2005.05.062
• 作为产物：
  描述：

  4-(三氟甲基)亚苯基肼 在 2,2,6,6-tetramethylpiperidinyl-lithium 作用下， 以 四氢呋喃 、 甲苯 、 xylene 为溶剂， 生成 (S)-2-{(R)-2,2-Dimethyl-1-[5-(4-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propoxycarbonylamino}-hexanoic acid methyl ester
  参考文献：
  名称：

  P2–P3 conformationally constrained ketoamide-based inhibitors of cathepsin K

  摘要：

  An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.

  DOI：

  10.1016/j.bmcl.2005.05.062

文献信息

• Alpha-ketoamide derivatives as cathepsin k inhibitors
  申请人：Barrett David Gene

  公开号：US20050107616A1

  公开（公告）日：2005-05-19

  Biaryl ketoamide derivatives, which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such biaryl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文介绍了用作猫hepsin K抑制剂的联苯基酮酰胺衍生物。所述发明还包括制备这种联苯基酮酰胺衍生物的方法，以及将其用于治疗与增强骨转换有关的疾病，包括骨质疏松症，该疾病最终可能导致骨折的方法。
• P2–P3 conformationally constrained ketoamide-based inhibitors of cathepsin K
  作者：David G. Barrett、Virginia M. Boncek、John G. Catalano、David N. Deaton、Anne M. Hassell、Cynthia H. Jurgensen、Stacey T. Long、Robert B. McFadyen、Aaron B. Miller、Larry R. Miller、J. Alan Payne、John A. Ray、Vicente Samano、Lisa M. Shewchuk、Francis X. Tavares、Kevin J. Wells-Knecht、Derril H. Willard、Lois L. Wright、Hui-Qiang Q. Zhou

  DOI：10.1016/j.bmcl.2005.05.062

  日期：2005.8

  An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.