tert-butyl 4-(3-tert-butylphenylcarbamoyl)-4-methylpiperidine-1-carboxylate | 1192189-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(3-tert-butylphenylcarbamoyl)-4-methylpiperidine-1-carboxylate
• 英文别名: tert-Butyl 4-(3-tert-butylphenylcarbamoyl)-4-methylpiperidine-1-carboxylate；tert-butyl 4-[(3-tert-butylphenyl)carbamoyl]-4-methylpiperidine-1-carboxylate
• CAS: 1192189-34-6
• 化学式: C₂₂H₃₄N₂O₃
• 分子量: 374.524
• InChiKey: OCPHZILUPWGHQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-tert-butylphenylcarbamoyl)-4-methylpiperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 0.5h， 以100%的产率得到N-(3-tert-butylphenyl)-4-methylpiperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  LIMK2 INHIBITORS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE

  摘要：

  LIM激酶2的抑制剂已被披露，以及包含它们的药物组合物和它们的使用方法。特定化合物的化学式如下：

  公开号：

  US20090264450A1
• 作为产物：
  描述：

  tert-butyl 4-(chlorocarbonyl)-4-methylpiperidine-1-carboxylate 、 3-叔丁基苯胺 在 吡啶 作用下， 以 1,1-二氯乙烷 为溶剂， 反应 1.0h， 生成 tert-butyl 4-(3-tert-butylphenylcarbamoyl)-4-methylpiperidine-1-carboxylate
  参考文献：
  名称：

  LIMK2 INHIBITORS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE

  摘要：

  LIM激酶2的抑制剂已被披露，以及包含它们的药物组合物和它们的使用方法。特定化合物的化学式如下：

  公开号：

  US20090264450A1

文献信息

• LIMK2 inhibitors, compositions comprising them, and methods of their use
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：US08193202B2

  公开（公告）日：2012-06-05

  Inhibitors of LIM kinase 2 are disclosed, along with pharmaceutical compositions comprising them and methods of their use. Particular compounds are of the formula:

  本发明揭示了LIM激酶2的抑制剂，以及包含它们的制药组合物和它们的使用方法。特别的化合物的化学式如下：
• Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the Treatment of Glaucoma
  作者：Bryce A. Harrison、Zheng Y. Almstead、Hugh Burgoon、Michael Gardyan、Nicole C. Goodwin、Jason Healy、Ying Liu、Ross Mabon、Brett Marinelli、Lakshman Samala、Yulian Zhang、Terry R. Stouch、N. Andrew Whitlock、Suma Gopinathan、Beth McKnight、Shuli Wang、Nita Patel、Alan G. E. Wilson、Brian D. Hamman、Dennis S. Rice、David B. Rawlins

  DOI：10.1021/ml500367g

  日期：2015.1.8

  The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment of ocular hypertension and associated glaucoma, is disclosed. Previously reported LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of the central urea. Replacement of the urea with a hindered amide resulted in aqueous stable compounds, and addition of solubilizing groups resulted in a set of compounds with good properties for topical dosing in the eye and good efficacy in a mouse model of ocular hypertension. LX7101 was selected as a clinical candidate from this group based on superior efficacy in lowering intraocular pressure and a good safety profile. LX7101 completed IND enabling studies and was tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy in lowering intraocular pressure.