(1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylic acid | 819858-50-9

• 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,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylic acid
• 英文别名: (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexane-1-carboxylic acid
• CAS: 819858-50-9
• 化学式: C₁₃H₁₃BrF₂O₂
• 分子量: 319.146
• InChiKey: MYNZJROVUABSOU-WCBMZHEXSA-N

物化性质

• 沸点：
  392.9±42.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylic acid 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 (1R,2R)-N-(cyanomethyl)-5,5-difluoro-2-[4'-(methylthio)-1,1'-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 、 lithium hydroxide 、 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 69.17h， 生成 (1R,2R)-2-(2-bromophenyl)-5,5-difluorocyclohexanecarboxylic acid
  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。
• Cathepsin cysteine protease inhibitors
  申请人：Bayly Christopher

  公开号：US20070167635A1

  公开（公告）日：2007-07-19

  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.

  本发明涉及一类具有通式(I)的化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普西林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，例如骨质疏松症。
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS
  申请人：Merck Canada Inc.

  公开号：EP1644326B1

  公开（公告）日：2016-11-02
• US7405229B2
  申请人：——

  公开号：US7405229B2

  公开（公告）日：2008-07-29