3-(thien-3-yl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl)-pyrazolo(1,5-A)pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(thien-3-yl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl)-pyrazolo(1,5-A)pyrimidine
• 英文别名: 3-(3-thienyl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl) pyrazolo(1,5-A)pyrimidine；3-(thien-3-yl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl)pyrazolo(1,5-A)pyrimidine；3-(3-thienyl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl)pyrazolo(1,5-A)pyrimidine；Pyrazolo[1,5-a]pyrimidine 4a；4-[2-[4-(3-thiophen-3-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenoxy]ethyl]morpholine
• 化学式: C₂₂H₂₂N₄O₂S
• 分子量: 406.508
• InChiKey: YUAOWJBCURIMGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-噻吩乙腈 在 2,4,6-三甲基吡啶 、 2,4-滴二甲胺盐 、 caesium carbonate 、 溶剂黄146 、 sodium iodide 、 lithium iodide 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 3-(thien-3-yl)-6-(4-(2-(4-morpholinyl)ethoxy)phenyl)-pyrazolo(1,5-A)pyrimidine
  参考文献：
  名称：

  Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics

  摘要：

  We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.(C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00827-2

文献信息

• Method of treating cancer
  申请人：——

  公开号：US20020041880A1

  公开（公告）日：2002-04-11

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of angiogenesis, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of angiogenesis. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA结合物和一种抑制血管生成的化合物的组合治疗癌症的方法，该方法包括向所述哺乳动物施用至少两种治疗剂量，这些治疗剂量选自一组化合物，其中一种是PSA结合物，另一种是抑制血管生成的化合物，这些治疗剂量可以顺序给药或同时给药，本发明还涉及制备这种组合物的方法。
• Angiogenesis inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06235741B1

  公开（公告）日：2001-05-22

  The present invention relates to compounds which inhibit tyrosine kinase enzymes, compositions which contain tyrosine kinase inhibiting compounds and methods of using tyrosine kinase inhibitors to treat tyrosine kinase-dependent diseases/conditions such as angiogenenesis, cancer, atherosclerosis, diabetic retinopathy or autoimmune diseases, in mammals.

  本发明涉及抑制酪氨酸激酶酶的化合物，含有酪氨酸激酶抑制化合物的组合物以及使用酪氨酸激酶抑制剂治疗哺乳动物中的酪氨酸激酶依赖性疾病/病状，如血管生成、癌症、动脉硬化、糖尿病视网膜病变或自身免疫疾病的方法。
• NOVEL ANGIOGENESIS INHIBITORS
  申请人：MERCK & CO., INC.

  公开号：EP0984692A1

  公开（公告）日：2000-03-15
• EP0984692A4
  申请人：——

  公开号：EP0984692A4

  公开（公告）日：2001-02-21
• US6235741B1
  申请人：——

  公开号：US6235741B1

  公开（公告）日：2001-05-22