(4R,5R)-2,2-dimethyl-5-[[(1R)-1-(4-pyrazol-1-ylphenyl)ethyl]carbamoyl]-1,3-dioxolane-4-carboxylic acid | 871730-11-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4R,5R)-2,2-dimethyl-5-[[(1R)-1-(4-pyrazol-1-ylphenyl)ethyl]carbamoyl]-1,3-dioxolane-4-carboxylic acid
• CAS: 871730-11-9
• 化学式: C₁₈H₂₁N₃O₅
• 分子量: 359.382
• InChiKey: HXELLQVCUBYKQP-KCPJHIHWSA-N

物化性质

• 沸点：
  608.2±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-2-(piperidin-1-yl)-4-(pyrrolidin-2-yl)thiazole 、 (4R,5R)-2,2-dimethyl-5-[[(1R)-1-(4-pyrazol-1-ylphenyl)ethyl]carbamoyl]-1,3-dioxolane-4-carboxylic acid 在 盐酸 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3R)-N-((R)-1-(4-(1H-pyrazol-1-yl)phenyl)ethyl)-2,3-dihydroxy-4-oxo-4-((R)-2-(2-(piperidin-1-yl)thiazol-4-yl)pyrrolidin-1-yl)butanamide
  参考文献：
  名称：

  2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors

  摘要：

  TNF-alpha converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.01.002
• 作为产物：
  描述：

  (4R,5R)-5-(methoxycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid 在 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4R,5R)-2,2-dimethyl-5-[[(1R)-1-(4-pyrazol-1-ylphenyl)ethyl]carbamoyl]-1,3-dioxolane-4-carboxylic acid
  参考文献：
  名称：

  2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors

  摘要：

  TNF-alpha converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.01.002

文献信息

• Compounds for the treatment of inflammatory disorders
  申请人：Siddiqui Arshad M.

  公开号：US20060178366A1

  公开（公告）日：2006-08-10

  This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, aggrecanase, ADMP, LpxC, ADAMs, TACE, TNF-α or combinations thereof.

  本发明涉及式（I）的化合物：或其药学上可接受的盐、溶剂或异构体，可用于治疗由MMPs、aggrecanase、ADMP、LpxC、ADAMs、TACE、TNF-α或其组合介导的疾病或病况。
• Compounds for the treatment of inflammatory disorders and microbial diseases
  申请人：Siddiqui Arshad M.

  公开号：US20070167426A1

  公开（公告）日：2007-07-19

  This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, aggrecanase, ADMP, LpxC, ADAMs, TACE, TNF-α or combinations thereof.

  本发明涉及式(I)的化合物：或其药学上可接受的盐、溶剂或异构体，可用于治疗由MMPs、aggrecanase、ADMP、LpxC、ADAMs、TACE、TNF-α或其组合介导的疾病或病况。
• COMPOUNDS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  申请人：Guo Zhuyan

  公开号：US20100145048A1

  公开（公告）日：2010-06-10

  This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, TNF-α or combinations thereof.

  本发明涉及公式(I)的化合物：或其药学上可接受的盐、溶剂化合物或异构体，可用于治疗由MMPs、ADAMs、TACE、TNF-α或其组合介导的疾病或病症。
• US7638513B2
  申请人：——

  公开号：US7638513B2

  公开（公告）日：2009-12-29
• US7652020B2
  申请人：——

  公开号：US7652020B2

  公开（公告）日：2010-01-26