(1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylthio)biphenyl-2-yl]cyclohexanecarboxamide

• 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: (1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylthio)biphenyl-2-yl]cyclohexanecarboxamide
• 英文别名: (1R,2R)-N-(cyanomethyl)-2-{2-[4-(methylsulfanyl)phenyl]phenyl}cyclohexane-1-carboxamide；(1R,2R)-N-(cyanomethyl)-2-[2-(4-methylsulfanylphenyl)phenyl]cyclohexane-1-carboxamide
• 化学式: C₂₂H₂₄N₂OS
• 分子量: 364.511
• InChiKey: UKQULZSZDDFLST-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylthio)biphenyl-2-yl]cyclohexanecarboxamide 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylsulfinyl)biphenyl-2-yl]cyclohexanecarboxamide 、 (1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylsulfonyl)biphenyl-2-yl]cyclohexanecarboxamide
  参考文献：
  名称：

  β-Substituted Cyclohexanecarboxamide:  A Nonpeptidic Framework for the Design of Potent Inhibitors of Cathepsin K

  摘要：

  A new series of nonpeptidic cathepsin K inhibitors that are based on a beta-substituted cyclohexanecarboxamide motif has been developed. Lead optimization yielded compounds with sub-nanomolar potency and exceptional selectivity profiles against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the cyclohexyl ring led to compounds with excellent pharmacokinetic properties. Considering the well-established role of cathepsin K in osteoclast-mediated bone turnover, compounds such as (-)-34a (hrab Cat K IC50 0.28 nM; > 800-fold selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit great potential for development as an orally bioavailable therapeutic for treatment of diseases that involve bone loss.

  DOI：

  10.1021/jm051059p
• 作为产物：
  描述：

  邻溴肉桂酸 在 palladium on activated charcoal 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 sodium carbonate 、 三乙胺 、 对苯二酚 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 54.0h， 生成 (1R/S,2R/S)-N-(cyanomethyl)-2-[4'-(methylthio)biphenyl-2-yl]cyclohexanecarboxamide
  参考文献：
  名称：

  β-Substituted Cyclohexanecarboxamide:  A Nonpeptidic Framework for the Design of Potent Inhibitors of Cathepsin K

  摘要：

  A new series of nonpeptidic cathepsin K inhibitors that are based on a beta-substituted cyclohexanecarboxamide motif has been developed. Lead optimization yielded compounds with sub-nanomolar potency and exceptional selectivity profiles against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the cyclohexyl ring led to compounds with excellent pharmacokinetic properties. Considering the well-established role of cathepsin K in osteoclast-mediated bone turnover, compounds such as (-)-34a (hrab Cat K IC50 0.28 nM; > 800-fold selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit great potential for development as an orally bioavailable therapeutic for treatment of diseases that involve bone loss.

  DOI：

  10.1021/jm051059p