tert-butyl [2-(1-ethyl-1H-imidazol-2-yl)-2-oxoethyl]carbamate | 911396-33-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl [2-(1-ethyl-1H-imidazol-2-yl)-2-oxoethyl]carbamate
• 英文别名: tert-butyl N-[2-(1-ethylimidazol-2-yl)-2-oxoethyl]carbamate
• CAS: 911396-33-3
• 化学式: C₁₂H₁₉N₃O₃
• 分子量: 253.301
• InChiKey: MKPHXTRPWKXXBK-UHFFFAOYSA-N

物化性质

• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [2-(1-ethyl-1H-imidazol-2-yl)-2-oxoethyl]carbamate 在 盐酸 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (S)-N-((4-(1-ethyl-1H-imidazol-2-yl)-2,5-dioxoimidazolidin-4-yl)-methyl)-5-(trifluoromethyl)benzofuran-2-carboxamide
  参考文献：
  名称：

  Use of Osmotic Pumps to Establish the Pharmacokinetic–Pharmacodynamic Relationship and Define Desirable Human Performance Characteristics for Aggrecanase Inhibitors

  摘要：

  The development of reliable relationships between in vivo target engagement, pharmacodynamic activity, and efficacy in chronic disease models is beneficial for enabling hypothesis-driven drug discovery and facilitating the development of patient-focused candidate selection criteria. Toward those ends, osmotic infusion pumps can be useful for overcoming limitations in the PK properties of proof-of-concept (POC) compounds to accelerate the development of such relationships. In this report, we describe the application of this strategy to the development of hydantoin-derived aggrecanase inhibitors (eg, 3) for the treatment of osteoarthiritis (OA). Potent, selective inhibitors were efficacious in both chemical and surgical models of OA when exposures were sustained in excess of 10 times the plasma IC50. The use of these data for establishing patient-focused candidate selection criteria is exemplified with the characterization of compound 8, which is projected to sustain the desired level of target engagement at a dose of 45 mg qd.

  DOI：

  10.1021/acs.jmedchem.6b00398
• 作为产物：
  描述：

  1-乙基咪唑 、 N-(叔丁氧基羰基)甘氨酸-N′-甲氧基-N′-甲酰胺 在 叔丁基锂 作用下， 以 四氢呋喃 为溶剂， 以46%的产率得到tert-butyl [2-(1-ethyl-1H-imidazol-2-yl)-2-oxoethyl]carbamate
  参考文献：
  名称：

  Use of Osmotic Pumps to Establish the Pharmacokinetic–Pharmacodynamic Relationship and Define Desirable Human Performance Characteristics for Aggrecanase Inhibitors

  摘要：

  The development of reliable relationships between in vivo target engagement, pharmacodynamic activity, and efficacy in chronic disease models is beneficial for enabling hypothesis-driven drug discovery and facilitating the development of patient-focused candidate selection criteria. Toward those ends, osmotic infusion pumps can be useful for overcoming limitations in the PK properties of proof-of-concept (POC) compounds to accelerate the development of such relationships. In this report, we describe the application of this strategy to the development of hydantoin-derived aggrecanase inhibitors (eg, 3) for the treatment of osteoarthiritis (OA). Potent, selective inhibitors were efficacious in both chemical and surgical models of OA when exposures were sustained in excess of 10 times the plasma IC50. The use of these data for establishing patient-focused candidate selection criteria is exemplified with the characterization of compound 8, which is projected to sustain the desired level of target engagement at a dose of 45 mg qd.

  DOI：

  10.1021/acs.jmedchem.6b00398

文献信息

• SUBSTITUTED ARYLOXOETHYL CYCLOPROPANECARBOXAMIDE COMPOUNDS AS VR1 RECEPTOR ANTAGONISTS
  申请人：Hanazawa Takeshi

  公开号：US20110152326A1

  公开（公告）日：2011-06-23

  This invention provides a compound of the formula (I): (I) These compounds are useful for the treatment of disease conditions caused by overactivation of the VR1 receptor, such as pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了一种公式(I)的化合物：(I)。这些化合物对于治疗由VR1受体过度激活引起的疾病状况，如哪些疼痛等在哺乳动物中非常有用。此发明还提供了包含上述化合物的药物组合物。
• Use of Osmotic Pumps to Establish the Pharmacokinetic–Pharmacodynamic Relationship and Define Desirable Human Performance Characteristics for Aggrecanase Inhibitors
  作者：Michael R. Wiley、Timothy B. Durham、Lisa A. Adams、Mark G. Chambers、Chaohua Lin、Chin Liu、Jothirajah Marimuthu、Peter G. Mitchell、Daniel R. Mudra、Craig A. Swearingen、James L. Toth、Jennifer M. Weller、Kannan Thirunavukkarasu

  DOI：10.1021/acs.jmedchem.6b00398

  日期：2016.6.23

  The development of reliable relationships between in vivo target engagement, pharmacodynamic activity, and efficacy in chronic disease models is beneficial for enabling hypothesis-driven drug discovery and facilitating the development of patient-focused candidate selection criteria. Toward those ends, osmotic infusion pumps can be useful for overcoming limitations in the PK properties of proof-of-concept (POC) compounds to accelerate the development of such relationships. In this report, we describe the application of this strategy to the development of hydantoin-derived aggrecanase inhibitors (eg, 3) for the treatment of osteoarthiritis (OA). Potent, selective inhibitors were efficacious in both chemical and surgical models of OA when exposures were sustained in excess of 10 times the plasma IC50. The use of these data for establishing patient-focused candidate selection criteria is exemplified with the characterization of compound 8, which is projected to sustain the desired level of target engagement at a dose of 45 mg qd.