(2R)-3-methyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-ol | 863651-39-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R)-3-methyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-ol
• CAS: 863651-39-2
• 化学式: C₁₃H₁₆N₂O₂
• 分子量: 232.282
• InChiKey: WCTACGMGEBLDAR-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-3-methyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-ol 在 4-二甲氨基吡啶 、 lithium hydroxide 、 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 、 甲苯 为溶剂， 生成 [(2R)-3-methyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-yl] N-[(3S)-1-cyano-2-oxo-1-(triphenyl-lambda5-phosphanylidene)heptan-3-yl]carbamate
  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：

  苯甲酰肼 在 2,2,6,6-tetramethylpiperidinyl-lithium 作用下， 以 四氢呋喃 、 xylene 为溶剂， 生成 (2R)-3-methyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-ol
  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

• [EN] ALPHA-KETOAMIDE DERIVATIVES AS CATHEPSIN K INHIBITORS<br/>[FR] DERIVES D'ALPHA-CETOAMIDE UTILISES EN TANT QU'INHIBITEURS DE LA CATHEPSINE K
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003013518A1

  公开（公告）日：2003-02-20

  Biaryl ketoamide derivatives (I), 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.

  本文描述了有用于作为蛋白酶K抑制剂的双芳基酮酰胺衍生物(I)。所述的发明还包括制备这种双芳基酮酰胺衍生物的方法，以及在治疗与增强骨转换相关的疾病，包括骨质疏松症，最终可能导致骨折的方法。
• ALPHA-KETOAMIDE DERIVATIVES AS CATHEPSIN K INHIBITORS
  申请人：SmithKline Beecham Corporation

  公开号：EP1411933A1

  公开（公告）日：2004-04-28
• 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.