methyl 1-(4-bromophenyl)-5-oxo-4H-pyrazole-3-carboxylate | 1195985-58-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 1-(4-bromophenyl)-5-oxo-4H-pyrazole-3-carboxylate
• CAS: 1195985-58-0
• 化学式: C₁₁H₉BrN₂O₃
• 分子量: 297.108
• InChiKey: SHKOEQDZIPDWII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-bromophenyl)-5-oxo-4H-pyrazole-3-carboxylate 在 titanium(IV) isopropylate 、 正丁基锂 、 偶氮二甲酸二异丙酯 、 水 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 5.33h， 生成 4-(3-((R)-1((R)-(3-chlorophenyl)ethylanamino)ethyl)-5-methoxy-1H-pyrazol-1-yl)benzoic acid
  参考文献：
  名称：

  Discovery and Optimization of Substituted 1-(1-Phenyl-1H-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics

  摘要：

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.

  DOI：

  10.1021/jm9012278
• 作为产物：
  描述：

  丁炔二酸二甲酯 、 对溴苯肼 在 sodium methylate 作用下， 以 乙醚 、 甲醇 为溶剂， 反应 3.5h， 以64%的产率得到methyl 1-(4-bromophenyl)-5-oxo-4H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Discovery and Optimization of Substituted 1-(1-Phenyl-1H-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics

  摘要：

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.

  DOI：

  10.1021/jm9012278

文献信息

• Discovery of pyrazolone spirocyclohexadienone derivatives with potent antitumor activity
  作者：Lei Wang、Zixuan Yang、Tianyu Ni、Wencai Shi、Yunbo Guo、Keliang Li、Anzhe Shi、Shanchao Wu、Chunquan Sheng

  DOI：10.1016/j.bmcl.2019.126662

  日期：2020.1

  Starting from easy accessible pyrazoletetrahydropyran acetals, a series of new pyrazolone spirocyclohexadienone derivatives were synthesized and assayed for antitumor activity. Compound 10s was identified to possess good antitumor activity. It could induce MDA-MB-231 cancer cell apoptosis in a concentration dependent manner and arrest the cell cycle progression mainly at the G1 phase.

  从易于获得的吡唑四氢吡喃缩醛开始，合成了一系列新的吡唑啉酮螺环己二酮衍生物，并测定了其抗肿瘤活性。鉴定出化合物10s具有良好的抗肿瘤活性。它可以以浓度依赖的方式诱导MDA-MB-231癌细胞凋亡，并主要在G1期阻止细胞周期进程。
• Divergent Cascade Construction of Skeletally Diverse “Privileged” Pyrazole-Derived Molecular Architectures
  作者：Yongqiang Zhang、Shanchao Wu、Shengzheng Wang、Kun Fang、Guoqiang Dong、Na Liu、Zhenyuan Miao、Jianzhong Yao、Jian Li、Wannian Zhang、Chunquan Sheng、Wei Wang

  DOI：10.1002/ejoc.201403673

  日期：2015.3

  powerful divergent cascade strategy has been explored for the easy construction of diverse enantioenriched pyrazole-derived scaffolds from readily available chiral fused pyrazole-tetrahydropyran acetals. These versatile intermediates can react in various ways to give Michael–aldol, reduction–lactonization, α-hydroxylation–acetalization–oxidation, and Wittig–aldol and Wittig–oxa-Michael cascade reactions

  已经探索了一种强大的发散级联策略，可以从容易获得的手性稠合吡唑-四氢吡喃缩醛轻松构建多种对映体富集的吡唑衍生支架。这些多功能中间体可以以各种方式反应，产生迈克尔-羟醛、还原-内酯化、α-羟基化-缩醛化-氧化以及 Wittig-aldol 和 Wittig-oxa-Michael 级联反应。仅使用六个简单的构建块，这些过程就产生了五种不同的分子结构。此外，筛选代表 5 种不同支架的 10 种化合物揭示了值得进一步开发的有效抗癌先导化合物。
• Discovery and Optimization of Substituted 1-(1-Phenyl-1<i>H</i>-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics
  作者：Steve F. Poon、David J. St. Jean、Paul E. Harrington、Charles Henley、James Davis、Sean Morony、Fred D. Lott、Jeff D. Reagan、Jenny Ying-Lin Lu、Yuhua Yang、Christopher Fotsch

  DOI：10.1021/jm9012278

  日期：2009.11.12

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.