3-(bromo)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine | 216661-83-5

• 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-(bromo)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine
• 英文别名: 3-(bromo)-6-(4-methoxyphenyl) pyrazolo(1,5-A)pyrimidine；3-(bromo)-6-(4-methoxyphenyl)pyrazolo(1,5-A)pyrimidine；3-Bromo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine
• CAS: 216661-83-5
• 化学式: C₁₃H₁₀BrN₃O
• 分子量: 304.146
• InChiKey: PEXKNSGOEOREKM-UHFFFAOYSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(bromo)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 氢溴酸 、 溶剂黄146 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 反应 4.67h， 生成 4-[3-(吡啶-4-基)吡唑并[1,5-A]嘧啶-6-基]苯酚
  参考文献：
  名称：

  极简主义末端含炔烃的二嗪基光交联剂的设计与合成及其在基于细胞和组织的蛋白质组谱分析的激酶抑制剂中的掺入

  摘要：

  少即是多：极简的“可点击”光交联剂（参见方案）与许多小分子激酶抑制剂结合在一起。所得的探针可用于体外（细胞裂解物）和原位（活细胞）蛋白质组分析，以大规模鉴定其潜在的细胞激酶靶标，并显示出比以前的探针更好的结果。

  DOI：

  10.1002/anie.201300683
• 作为产物：
  描述：

  6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 3-(bromo)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine
  参考文献：
  名称：

  Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors

  摘要：

  A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a] pyrimidine and pyrazolo[1,5-a] pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t(1/2) = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.052

文献信息

• Synthesis and Initial SAR Studies of 3,6-Disubstituted Pyrazolo[1,5-a]pyrimidines: A New Class of KDR Kinase Inhibitors
  作者：Mark E. Fraley、William F. Hoffman、Robert S. Rubino、Randall W. Hungate、Andrew J. Tebben、Ruth Z. Rutledge、Rosemary C. McFall、William R. Huckle、Richard L. Kendall、Kathleen E. Coll、Kenneth A. Thomas

  DOI：10.1016/s0960-894x(02)00525-5

  日期：2002.10

  synthesized and evaluated the activity of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines as a new class of KDR kinase inhibitors. Starting with screening lead 1, potency against isolated KDR was fully optimized with 3-thienyl and 4-methoxyphenyl substituents at the 6- and 3-positions (3g, KDR IC(50)=19 nM), respectively. The synthesis and SAR of these compounds are described.

  我们已经合成并评估了3,6-二取代的吡唑并[1,5-a]嘧啶作为一类新的KDR激酶抑制剂的活性。从筛选铅1开始，分别在6位和3位（3g，KDR IC（50）= 19 nM）处使用3-噻吩基和4-甲氧基苯基取代基完全优化了对分离的KDR的效力。描述了这些化合物的合成和SAR。
• 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。
• Treatment of Alzheimer's Disease and Related Conditions
  申请人：Churcher Ian

  公开号：US20100240647A1

  公开（公告）日：2010-09-23

  Compounds of formula (I) inhibit microtubule affinity regulating kinase (MARK), and hence are suitable for treating diseases associated with abnormal phosphorylation of tau.

  式(I)的化合物抑制微管亲和力调节激酶（MARK），因此适用于治疗与tau异常磷酸化相关的疾病。
• 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