4-(3-Pyridin-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-phenol | 515880-86-1

• 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: 4-(3-Pyridin-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-phenol
• 英文别名: 4-(3-pyridin-3-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenol
• CAS: 515880-86-1
• 化学式: C₁₇H₁₂N₄O
• 分子量: 288.308
• InChiKey: MFYRFDDAHRLWPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.16
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(2-氯乙基)哌啶 、 4-(3-Pyridin-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-phenol 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-3-ylpyrazolo[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
• 作为产物：
  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