ethyl 5-amino-1-[2-(4-fluorophenyl)-2-hydroxyethyl]-1H-pyrazole-4-carboxylate | 959772-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-amino-1-[2-(4-fluorophenyl)-2-hydroxyethyl]-1H-pyrazole-4-carboxylate
• 英文别名: Ethyl 5-amino-1-[2-(4-fluorophenyl)-2-hydroxyethyl]pyrazole-4-carboxylate
• CAS: 959772-13-5
• 化学式: C₁₄H₁₆FN₃O₃
• 分子量: 293.298
• InChiKey: QBRLTPFTAUMPQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 5-amino-1-[2-(4-fluorophenyl)-2-hydroxyethyl]-1H-pyrazole-4-carboxylate 在 硫酸 、 二苯基膦叠氮化物 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 生成 (2‐(4‐fluorophenyl)‐2,3‐dihydro‐1H‐imidazo[1,2‐b]pyrazol‐7‐yl)(piperidin‐1‐yl)methanone
  参考文献：
  名称：

  针对不同癌症和炎症通路的新型吡唑和咪唑-吡唑系列

  摘要：

  (1) 背景：不同的先前合成的吡唑类和咪唑并吡唑类显示出有趣的抗血管生成作用，能够以不同的方式和不同的效力干扰 ERK1/2、AKT 和 p38MAPK 的磷酸化；(2) 方法：在这里，合成了一个新的小化合物库，赋予相同不同装饰的化学支架，以获得能够抑制炎症、癌症和人血小板聚集的不同途径的新药物。(3)结果：大多数新合成的衍生物能够阻断血小板和人脐静脉内皮细胞(HUVEC)中的ROS产生、血小板聚集和p38MAPK磷酸化。这为开发具有抗血管生成活性的新药剂铺平了道路。

  DOI：

  10.3390/molecules26195735
• 作为产物：
  描述：

  1-(4-fluorophenyl)-2-hydrazinoethanol 、 2-氰基-3-乙氧基丙烯酸乙酯 以 甲苯 为溶剂， 反应 8.0h， 以70%的产率得到ethyl 5-amino-1-[2-(4-fluorophenyl)-2-hydroxyethyl]-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  NEW 4-SUBSTITUTED DERIVATIVES OF PYRAZOLO[3,4-D PYRIMIDINE AND PYRROLO[2,3-D]PYRIMIDINE AND USES THEREOF

  摘要：

  本发明涉及具有以下式(I)的吡唑并[3,4-d]嘧啶或吡咯[2,3-d]嘧啶的化合物4-取代衍生物及其用途，特别是用于骨相关疾病和肿瘤的治疗。

  公开号：

  US20100249152A1

文献信息

• Identification of a Novel Pyrazolo[3,4-<i>d</i>]pyrimidine Able To Inhibit Cell Proliferation of a Human Osteogenic Sarcoma in Vitro and in a Xenograft Model in Mice
  作者：Fabrizio Manetti、Annalisa Santucci、Giada A. Locatelli、Giovanni Maga、Adriano Spreafico、Tommaso Serchi、Maurizio Orlandini、Giulia Bernardini、Nicola P. Caradonna、Andrea Spallarossa、Chiara Brullo、Silvia Schenone、Olga Bruno、Angelo Ranise、Francesco Bondavalli、Oskar Hoffmann、Mauro Bologna、Adriano Angelucci、Maurizio Botta

  DOI：10.1021/jm061449r

  日期：2007.11.1

  New pyrazolo[3,4-d]pyrimidines were synthesized and found to inhibit Src phosphorylation in a cell-free assay. Some of them significantly reduced the growth of human osteogenic sarcoma (SaOS-2) cells. The best compound, in terms of inhibitory properties toward both Src and SaOS-2 cells, was further investigated and found to reduce bone resorption when used to treat mouse osteoclasts, without interfering with normal osteoblast growth. Moreover, its metabolic stability prompted its study on a human SaOS-2 xenograft tumor model in nude mice, where the compound reduced significantly both the volume and weight of the tumor. These experimental findings make the new compound an interesting hit in the field of bone-related diseases.
• Structure-Based Optimization of Pyrazolo[3,4-<i>d</i>]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines
  作者：Fabrizio Manetti、Chiara Brullo、Matteo Magnani、Francesca Mosci、Beatrice Chelli、Emmanuele Crespan、Silvia Schenone、Antonella Naldini、Olga Bruno、Maria Letizia Trincavelli、Giovanni Maga、Fabio Carraro、Claudia Martini、Francesco Bondavalli、Maurizio Botta

  DOI：10.1021/jm701240c

  日期：2008.3.13

  Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and anti proliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.
• NEW 4-SUBSTITUTED DERIVATIVES OF PYRAZOLO [3,4-D] PYRIMIDINE AND PYRROLO [2,3-D] PYRIMIDINE AND USES THEREOF
  申请人：Universita Degli Studi di Siena

  公开号：EP2201013B1

  公开（公告）日：2014-11-19
• US8466164B2
  申请人：——

  公开号：US8466164B2

  公开（公告）日：2013-06-18
• NEW 4-SUBSTITUTED DERIVATIVES OF PYRAZOLO[3,4-D PYRIMIDINE AND PYRROLO[2,3-D]PYRIMIDINE AND USES THEREOF
  申请人：Schenone Silvia

  公开号：US20100249152A1

  公开（公告）日：2010-09-30

  The present invention relates to a compound 4-substituted derivative of pyrazolo[3,4-d]pyrimidine or of pyrrolo[2,3-d]pyrimidine having the formula (I) and uses thereof, in particular for the treatment of bone related diseases and tumours.

  本发明涉及具有以下式(I)的吡唑并[3,4-d]嘧啶或吡咯[2,3-d]嘧啶的化合物4-取代衍生物及其用途，特别是用于骨相关疾病和肿瘤的治疗。