(2R,3R)-N-((R)-1-(4-(1H-pyrazol-1-yl)phenyl)ethyl)-4-((R)-2-(2-(cyclopropylamino)thiazol-4-yl)pyrrolidin-1-yl)-2,3-dihydroxy-4-oxobutanamide | 1310416-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2R,3R)-N-((R)-1-(4-(1H-pyrazol-1-yl)phenyl)ethyl)-4-((R)-2-(2-(cyclopropylamino)thiazol-4-yl)pyrrolidin-1-yl)-2,3-dihydroxy-4-oxobutanamide
• 英文别名: (2R,3R)-4-[(2R)-2-[2-(cyclopropylamino)-1,3-thiazol-4-yl]pyrrolidin-1-yl]-2,3-dihydroxy-4-oxo-N-[(1R)-1-(4-pyrazol-1-ylphenyl)ethyl]butanamide
• CAS: 1310416-77-3
• 化学式: C₂₅H₃₀N₆O₄S
• 分子量: 510.617
• InChiKey: PRUCBZGVKSTGBL-FPHUIIFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-N-(tert-butoxycarbonyl)-2-(2-chloroacetyl)pyrrolidine 在 盐酸 、 甲醇 、 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)-4-((R)-2-(2-(cyclopropylamino)thiazol-4-yl)pyrrolidin-1-yl)-2,3-dihydroxy-4-oxobutanamide
  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

• 2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors
  作者：Chaoyang Dai、Dansu Li、Janeta Popovici-Muller、Lianyun Zhao、Vinay M. Girijavallabhan、Kristin E. Rosner、Brian J. Lavey、Razia Rizvi、Bandarpalle B. Shankar、Michael K.C. Wong、Zhuyan Guo、Peter Orth、Corey O. Strickland、Jing Sun、Xiaoda Niu、Shiying Chen、Joseph A. Kozlowski、Daniel J. Lundell、John J. Piwinski、Neng-Yang Shih、M. Arshad Siddiqui

  DOI：10.1016/j.bmcl.2011.01.002

  日期：2011.5

  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.