(1S,2S,3R,4R)-3-[[5-fluoro-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,2S,3R,4R)-3-[[5-fluoro-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide
• 化学式: C₁₆H₁₈FN₇O
• 分子量: 343.364
• InChiKey: HWPSHUSYXFAEGR-FIDNZITISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl exo-4-oxo-3-azatricyclo[4.2.1.02,5]non-7-ene-3-carboxylate 在 盐酸 、 ammonium hydroxide 、 碳酸氢钠 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 生成 (1S,2S,3R,4R)-3-[[5-fluoro-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide
  参考文献：
  名称：

  Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases

  摘要：

  In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly ip dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.067

文献信息

• PYRIMIDINE INHIBITORS OF KINASES
  申请人：Curtin Michael

  公开号：US20100317680A1

  公开（公告）日：2010-12-16

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A 1 , A 2 , A 3 , A 4 , X and Y are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as aurora and KDR.

  本发明涉及式(I)的化合物或药用可接受的盐，其中A1、A2、A3、A4、X和Y在描述中有定义。本发明还涉及制备所述化合物的方法，以及含有所述化合物的组合物，用于抑制aurora和KDR等激酶。
• COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS INCLUDING SUBSTITUTED NAPHTHALIMIDES SUCH AS AMONAFIDE FOR THE TREATMENT OF IMMUNOLOGICAL, METABOLIC, INFECTIOUS, AND BENIGN OR NEOPLASTIC HYPERPROLIFERATIVE DISEASE CONDITIONS
  申请人：BROWN Dennis M.

  公开号：US20160067241A1

  公开（公告）日：2016-03-10

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to naphthalimides such as amonafide or analogs, derivatives, or prodrugs thereof.
• US8426408B2
  申请人：——

  公开号：US8426408B2

  公开（公告）日：2013-04-23
• Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases
  作者：Michael L. Curtin、H. Robin Heyman、Robin R. Frey、Patrick A. Marcotte、Keith B. Glaser、James R. Jankowski、Terrance J. Magoc、Daniel H. Albert、Amanda M. Olson、David R. Reuter、Jennifer J. Bouska、Debra A. Montgomery、Joann P. Palma、Cherrie K. Donawho、Kent D. Stewart、Chris Tse、Michael R. Michaelides

  DOI：10.1016/j.bmcl.2012.05.067

  日期：2012.7

  In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly ip dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents. (C) 2012 Elsevier Ltd. All rights reserved.