6-(4-甲氧基-苯基)-3-吡啶-3-基-吡唑并[1,5-a]嘧啶 | 216661-72-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-(4-甲氧基-苯基)-3-吡啶-3-基-吡唑并[1,5-a]嘧啶
• 中文别名: 6-(4-甲氧基苯基)-3-(吡啶-3-基)吡唑并[1,5-A]嘧啶
• 英文名称: 3-(pyridin-3-yl)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine
• 英文别名: 3-(pyridin-3-yl)-6-(4-methoxyphenyl)pyrazolo(1,5-A)pyrimidine；3-(3-pyridyl)-6-(4-methoxyphenyl) pyrazolo(1,5-A)pyrimidine；3-(3-pyridyl)-6-(4-methoxyphenyl)pyrazolo(1,5-A)pyrimidine；6-(4-Methoxyphenyl)-3-(pyridin-3-yl)pyrazolo[1,5-a]pyrimidine；6-(4-methoxyphenyl)-3-pyridin-3-ylpyrazolo[1,5-a]pyrimidine
• CAS: 216661-72-2
• 化学式: C₁₈H₁₄N₄O
• 分子量: 302.335
• InChiKey: KEAIZNUXWMQAGK-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  室温下应存放在干燥且密封的环境中。

反应信息

• 作为反应物：
  描述：

  6-(4-甲氧基-苯基)-3-吡啶-3-基-吡唑并[1,5-a]嘧啶 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.17h， 生成 4-(3-Pyridin-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-phenol
  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
• 作为产物：
  描述：

  3-吡啶乙腈 在 四(三苯基膦)钯 、 氢溴酸肼 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 6-(4-甲氧基-苯基)-3-吡啶-3-基-吡唑并[1,5-a]嘧啶
  参考文献：
  名称：

  Development of a Reproducible and Scalable Method for the Synthesis of Biologically Active Pyrazolo[1,5-a]pyrimidine Derivatives

  摘要：

  摘要 为合成一系列 3,6 取代的吡唑并[1,5-a]嘧啶开发了一种可重复和可扩展的方法，该方法是合理设计 AMP 活化蛋白激酶选择性抑制剂的基础。关于新型碳骨架的形成，利用布赫瓦尔德配体在 5,7 二甲基取代的吡唑并[1,5-a]嘧啶的立体受阻位置 6 上形成 C-C 键的 Suzukii-Miyaura 交叉偶联的适用性已经得到证明。

  DOI：

  10.1134/s1070363223050043

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。
• Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics
  作者：Mark E. Fraley、Robert S. Rubino、William F. Hoffman、Scott R. Hambaugh、Kenneth L. Arrington、Randall W. Hungate、Mark T. Bilodeau、Andrew J. Tebben、Ruth Z. Rutledge、Richard L. Kendall、Rosemary C. McFall、William R. Huckle、Kathleen E. Coll、Kenneth A. Thomas

  DOI：10.1016/s0960-894x(02)00827-2

  日期：2002.12

  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.
• 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