methyl (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylate | 819858-49-6

• 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: methyl (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylate
• 英文别名: methyl (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexane-1-carboxylate
• CAS: 819858-49-6
• 化学式: C₁₄H₁₅BrF₂O₂
• 分子量: 333.173
• InChiKey: HOQXKBULZAGMGN-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylate 在 lithium hydroxide 、 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 、 sodium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 (1R,2R)-N-(cyanomethyl)-5,5-difluoro-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 chromium(VI) oxide 、 potassium dihydrogenphosphate 、 三甲基溴硅烷 、 二乙胺基三氟化硫 、 硫酸 、 (S)-(-)- α-甲基苄胺 、 二甲基亚砜 、 对苯二酚 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 丙酮 、 甲苯 为溶剂， 反应 54.17h， 生成 methyl (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylate
  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

• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA CATHEPSINE CYSTEINE PROTEASE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2005000800A1

  公开（公告）日：2005-01-06

  This invention relates to a class of compounds having the general formula (I) which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类具有一般式（I）的化合物，这些化合物是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• 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.