(1R/S,2R/S)-(2-{[(cyanomethyl)amino]carbonyl}-cyclohexyl)methyl-4-methylbenzenesulfonate

• 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)-(2-{[(cyanomethyl)amino]carbonyl}-cyclohexyl)methyl-4-methylbenzenesulfonate
• 英文别名: ((1R,2R)-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)methyl 4-methylbenzenesulfonate；[(1R,2R)-2-(cyanomethylcarbamoyl)cyclohexyl]methyl 4-methylbenzenesulfonate
• 化学式: C₁₇H₂₂N₂O₄S
• 分子量: 350.439
• InChiKey: BRXLUHUFEISNTF-GOEBONIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R/S,2R/S)-(2-{[(cyanomethyl)amino]carbonyl}-cyclohexyl)methyl-4-methylbenzenesulfonate 在 palladium on activated charcoal 超重氢 、 Oxone 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~40.0 ℃ 、79.73 kPa 条件下， 反应 23.0h， 生成 (1R,2R)-N-(cyanomethyl)-2-[[4-(trifluoromethoxy)-2-tritiophenyl]sulfonylmethyl]cyclohexane-1-carboxamide
  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：

  (1S,2S)-trans-1,2-cyclohexanedicarboxylic anhydride 在 N-甲基吗啉 、 吡啶 、 4-二甲氨基吡啶 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 21.08h， 生成 (1R/S,2R/S)-(2-{[(cyanomethyl)amino]carbonyl}-cyclohexyl)methyl-4-methylbenzenesulfonate
  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

文献信息

• Cyanoalkylamino derivatives as protease inhibitors
  申请人：Black Cameron

  公开号：US20050014941A1

  公开（公告）日：2005-01-20

  The present invention is directed to novel cyanoalkylamino derivatives that are inhibitors of cysteine protease such as cathepsins K, S, B and L, in particular cathepsin K Pharmaceutical composition comprising these compounds, method of treating diseases mediated by unregulated cysteine protease activity, in particular cathepsin K utilizing these compounds and methods of preparing these compounds are also disclosed.

  本发明涉及一种新型的氰基烷基氨基衍生物，其为半胱氨酸蛋白酶抑制剂，例如cathepsin K、S、B和L，特别是cathepsin K。本发明还涉及包含这些化合物的药物组合物，治疗由不受调节的半胱氨酸蛋白酶活性介导的疾病的方法，特别是利用这些化合物治疗cathepsin K，以及制备这些化合物的方法。
• CYANOALKYLAMINO DERIVATIVES AS PROTEASE INHIBITORS
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1446115B1

  公开（公告）日：2008-02-27
• US7371747B2
  申请人：——

  公开号：US7371747B2

  公开（公告）日：2008-05-13
• β-Substituted Cyclohexanecarboxamide:  A Nonpeptidic Framework for the Design of Potent Inhibitors of Cathepsin K
  作者：Sheldon N. Crane、W. Cameron Black、James T. Palmer、Dana E. Davis、Eduardo Setti、Joel Robichaud、Julie Paquet、Renata M. Oballa、Christopher I. Bayly、Daniel J. McKay、John R. Somoza、Natalie Chauret、Carmai Seto、John Scheigetz、Greg Wesolowski、Frederic Massé、Sylvie Desmarais、Marc Ouellet

  DOI：10.1021/jm051059p

  日期：2006.2.1

  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.