1-(4-methoxybenzyl)-1H-thieno[3,2-d][1,3]oxazine-2,4-dione | 1086383-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(4-methoxybenzyl)-1H-thieno[3,2-d][1,3]oxazine-2,4-dione
• 英文别名: 1-[(4-Methoxyphenyl)methyl]thieno[3,2-d][1,3]oxazine-2,4-dione；1-[(4-methoxyphenyl)methyl]thieno[3,2-d][1,3]oxazine-2,4-dione
• CAS: 1086383-61-0
• 化学式: C₁₄H₁₁NO₄S
• 分子量: 289.312
• InChiKey: ONTPJHYNVVEOLP-UHFFFAOYSA-N

物化性质

• 熔点：
  181-182 °C
• 沸点：
  466.2±55.0 °C(Predicted)
• 密度：
  1.424±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxybenzyl)-1H-thieno[3,2-d][1,3]oxazine-2,4-dione 在 吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Design, synthesis and biological evaluation of thienopyridinones as Chk1 inhibitors

  摘要：

  A series of thienopyridinone derivatives was designed and synthesized as inhibitors of checkpoint kinase 1 (Chk1). Most of them exhibited moderate to good Chk1 inhibitory activities. Among them, compounds 8q, 8t, and 8w with excellent Chk1 inhibitory activities (IC50 values of 4.05, 6.23, and 2.33nM, respectively) displayed strong synergistic effects with melphalan, a DNA-damaging agent in the cell-based assay. Further kinase profiling indicated that compound 8t was highly selective against CDK2/cyclinA, Aurora A, and PKC.

  DOI：

  10.1016/j.bmc.2014.06.044
• 作为产物：
  描述：

  3-氨基-2-噻吩甲酸甲酯 在 potassium carbonate 、 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 0.92h， 生成 1-(4-methoxybenzyl)-1H-thieno[3,2-d][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  Design, synthesis and biological evaluation of thienopyridinones as Chk1 inhibitors

  摘要：

  A series of thienopyridinone derivatives was designed and synthesized as inhibitors of checkpoint kinase 1 (Chk1). Most of them exhibited moderate to good Chk1 inhibitory activities. Among them, compounds 8q, 8t, and 8w with excellent Chk1 inhibitory activities (IC50 values of 4.05, 6.23, and 2.33nM, respectively) displayed strong synergistic effects with melphalan, a DNA-damaging agent in the cell-based assay. Further kinase profiling indicated that compound 8t was highly selective against CDK2/cyclinA, Aurora A, and PKC.

  DOI：

  10.1016/j.bmc.2014.06.044

文献信息

• [EN] HPK1 INHIBITORS AND METHODS OF USING SAME<br/>[FR] INHIBITEURS DE HPK1 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV HEALTH NETWORK

  公开号：WO2016205942A1

  公开（公告）日：2016-12-29

  Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

  Thienopyridinone化合物的化学式（I）及其药用盐已被描述。在这些化合物中，X1、X2和X3中的一个是S，另外两个分别是独立的CR，其中R和所有其他变量如本文所定义。已证明这些化合物能抑制HPK1激酶活性并具有体内抗肿瘤活性。这些化合物可以有效地与药用载体以及其他免疫调节方法结合使用，例如检查点抑制或色氨酸氧化抑制剂。化学式（I）。
• Valuable Versatile Reactivity of Thiaisatoic Anhydrides: Expedient Solid­Phase Synthesis of Thieno[1,4]diazepine-2,5-diones
  作者：Vincent Lisowski、Yann Brouillette、Pascal Verdié、Jean Martinez

  DOI：10.1055/s-2008-1078210

  日期：——

  An expedient route for the generation of substituted thieno[3,2-e][1,4]diazepine-2,5-dione analogues is described herein. It was demonstrated in solution that thiaisatoic anhydride and its N-alkylated equivalents react in opposite ways with amino acids in basic conditions. This versatile reactivity was used to develop an efficient strategy on solid support. Wang resin-bound thiaisatoic anhydride was coupled with N-alkylated α-amino acids, cyclo-condensed and effectively cleaved from the polymer to provide a preliminary collection of thieno[3,2-e][1,4]diazepine-2,5-diones in 83-99% purity and 71-95% yield.

  本文描述了一种合成取代的噻吩并[3,2-e][1,4]二氮杂环庚烯-2,5-二酮类似物的便捷途径。在溶液中证明，硫代异硫氰酸酐及其N-烷基化类似物在碱性条件下与氨基酸发生相反的反应。利用这一多样的反应性，开发了一种高效的固相支持策略。Wang树脂结合的硫代异硫氰酸酐与N-烷基化的α-氨基酸反应，环化并有效地从聚合物中裂解，得到了纯度为83-99%、产率为71-95%的噻吩并[3,2-e][1,4]二氮杂环庚烯-2,5-二酮的初步集合。
• [EN] TRICYCLIC HPK1 INHIBITOR AND USE THEREOF<br/>[FR] INHIBITEUR DE HPK1 TRICYCLIQUE ET SON UTILISATION<br/>[ZH] 三并环类HPK1抑制剂及其用途
  申请人：SHANDONG XUANZHU PHARMA CO LTD

  公开号：WO2022188823A1

  公开（公告）日：2022-09-15

  本发明属于医药技术领域，具体涉及一类三并环类HPK1抑制剂化合物、其药学上可接受的盐或其立体异构体，含有所述化合物、其药学上可接受的盐或其异构体的药物组合物及制剂，制备所述化合物、其药学上可接受的盐或其立体异构体的方法，以及所述化合物、其药学上可接受的盐或其立体异构体的用途。
• HPK1 inhibitors and methods of using same
  申请人：University Health Network

  公开号：US11059832B2

  公开（公告）日：2021-07-13

  Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

  描述了式 (I) 的噻吩并吡啶酮化合物及其药学上可接受的盐类。在这些化合物中，X1、X2 和 X3 中的一个为 S，另外两个各自独立地为 CR，其中 R 和所有其他变量如本文所定义。研究表明，这些化合物可抑制 HPK1 激酶活性，并具有体内抗肿瘤活性。这些化合物可与药学上可接受的载体有效结合，也可与其他免疫调节方法结合，如检查点抑制或色氨酸氧化抑制剂。式 (I).
• HPK1 INHIBITORS AND METHODS OF USING SAME
  申请人：University Health Network

  公开号：EP3322711A1

  公开（公告）日：2018-05-23