2-(4-bromophenyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one | 1427158-06-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 英文名称: 2-(4-bromophenyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one
• 英文别名: 2-(4-bromophenyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one；2-(4-bromo-phenyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one
• CAS: 1427158-06-2
• 化学式: C₁₂H₈BrN₃O
• 分子量: 290.119
• InChiKey: XUOPPCRBNHMVHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-bromophenyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 cerium(III) chloride 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 20.0~100.0 ℃ 、400.01 kPa 条件下， 反应 18.0h， 生成 2-[4-(1-hydroxy-1-methylethyl)phenyl]-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one
  参考文献：
  名称：

  [EN] PYRROLOTRIAZINONE DERIVATIVES
  [FR] DÉRIVÉS DE PYRROLOTRIAZINONE

  摘要：

  公开号：

  WO2013164061A8
• 作为产物：
  描述：

  1-氨基-1H-吡咯-2-甲酰胺 在 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 147.0h， 生成 2-(4-bromophenyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one
  参考文献：
  名称：

  [EN] PYRROLOTRIAZINONE DERIVATIVES
  [FR] DÉRIVÉS DE PYRROLOTRIAZINONE

  摘要：

  公开号：

  WO2013164061A8

文献信息

• A tandem copper (II)-promoted synthesis of 2-substituted pyrrolo[2,1-f][1,2,4] triazin-4(3H)-ones
  作者：Yanhong Chen、Haoyue Xiang、Cun Tan、Yuyuan Xie、Chunhao Yang

  DOI：10.1016/j.tet.2013.02.004

  日期：2013.4

  annulation of 1-amino-1H-pyrrole-2-amides with various substituted benzaldehydes, heteroaryl aldehydes, alkyl aldehydes or even acetals, promoted by cupric chloride, to synthesize 2-substituted pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones is reported. This approach provides a useful method for constructing the privileged structure in medicinal chemistry. Electron-donating groups on both partners could accelerate

  一种有效的串联方法，用氯化铜促进1-氨基-1 H-吡咯-2-酰胺与各种取代的苯甲醛，杂芳基醛，烷基醛甚至乙缩醛的环合，合成2-取代的吡咯并[2,1-报告了f ] [1,2,4] triazin-4（3 H）-ones。该方法为构建药物化学中的特权结构提供了一种有用的方法。两个伙伴上的给电子基团可以加速反应。
• Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles
  作者：Jane Holmes、Thomas McGuire、Lynsie Almeida、Bernard Barlaam、Rosemary Croft、Allan Dishington、Laksmaiah Gingipalli、Lorraine Hassall、Janet Hawkins、Stephanos Ioannidis、Jeffrey Johannes、Jane Moore、Anil Patel、Kurt Pike、Timothy Pontz、Xiaoyun Wu、Tao Wang、Hai-Jun Zhang、Xiaolan Zheng

  DOI：10.1055/s-0035-1561355

  日期：——

  ◊ Current address: AstraZeneca R&D, Darwin Building (310), Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK Abstract Examples of hydroxymethylated analogues of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones are sparse or non-existent in the scientific literature. We have demonstrated

  ◊当前地址：英国剑桥CB4 0WG，剑桥米尔顿路，剑桥科学园，达尔文大厦（310），阿斯利康研发中心 抽象的 杂芳基核的羟甲基化类似物的实例，例如喹唑啉-4-酮，异喹啉-1（2 H）-酮，吡啶并[3,4- d ]嘧啶-4（3 H）-酮，铬-4-酮和吡咯烷酮[2,1- f ] [1,2,4]三嗪-4（3 H）-在科学文献中稀疏或不存在。我们已经证明，通过使用标准程序，可以从容易获得的原材料中获得此类化合物。 杂芳基核的羟甲基化类似物的实例，例如喹唑啉-4-酮，异喹啉-1（2 H）-酮，吡啶并[3,4- d ]嘧啶-4（3 H）-酮，铬-4-酮和吡咯烷酮[2,1- f ] [1,2,4]三嗪-4（3 H）-在科学文献中稀疏或不存在。我们已经证明，通过使用标准程序，可以从容易获得的原材料中获得此类化合物。
• PYRROLOTRIAZINONE DERIVATIVES
  申请人：Merck Patent GmbH

  公开号：US20150133453A1

  公开（公告）日：2015-05-14

  Compounds of the formula I in which X, R 1 and Y have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

  公式I的化合物中，X、R1和Y的含义如权利要求1所示，是Tankyrase的抑制剂，可用于治疗癌症、心血管疾病、中枢神经系统损伤和不同形式的炎症等疾病。
• Pyrrolotriazinone derivatives
  申请人：Merck Patent GmbH

  公开号：US09174995B2

  公开（公告）日：2015-11-03

  Compounds of the formula I in which X, R1 and Y have the meanings indicated in claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

  公式I的化合物中，X、R1和Y的含义如权利要求1所示，是坦克酶的抑制剂，可用于治疗癌症、心血管疾病、中枢神经系统损伤和不同形式的炎症等疾病。
• Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology
  作者：Jeffrey W. Johannes、Lynsie Almeida、Bernard Barlaam、P. Ann Boriack-Sjodin、Robert Casella、Rosemary A. Croft、Allan P. Dishington、Lakshmaiah Gingipalli、Chungang Gu、Janet L. Hawkins、Jane L. Holmes、Tina Howard、Jian Huang、Stephanos Ioannidis、Steven Kazmirski、Michelle L. Lamb、Thomas M. McGuire、Jane E. Moore、Derek Ogg、Anil Patel、Kurt G. Pike、Timothy Pontz、Graeme R. Robb、Nancy Su、Haiyun Wang、Xiaoyun Wu、Hai-Jun Zhang、Yue Zhang、Xiaolan Zheng、Tao Wang

  DOI：10.1021/ml5003663

  日期：2015.3.12

  The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germ line mutations of several Wnt pathway components, such as Axin, APC, and beta-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARE)) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclinical models of cancer and its impact on normal tissue, we sought a small molecule inhibitor of TNKS1/2 with suitable physicochemical properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-phenyl quinazolinone hit (compound 1), we discovered the pyrrolopyrimidinone compound 25 (AZ6102), which is a potent TNKS1/2 inhibitor that has 100 fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound 25 can be formulated well in a clinically relevant intravenous solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclinical species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms.