N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide | 1528743-17-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide
• 英文别名: N-(2,2-Difluoro-5H-1,3-dioxolo[4,5-f]benzoimidazole-6-yl)-3-methoxybenzamide；N-(2,2-difluoro-5H-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)-3-methoxybenzamide
• CAS: 1528743-17-0
• 化学式: C₁₆H₁₁F₂N₃O₄
• 分子量: 347.278
• InChiKey: KIXUMWAIYCKDQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.15
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.47
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  5-氨基-2,2-二氟-1,3-苯并二噁唑 在 nitronium tetrafluoborate 、 palladium on activated charcoal 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 环丁砜 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 100.0 ℃ 、379.22 kPa 条件下， 反应 89.0h， 生成 N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide
  参考文献：
  名称：

  碳11标记的CK1抑制剂的合成作为阿尔茨海默氏病成像的新潜在PET示踪剂

  摘要：

  参考标准品甲基3-（（（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2 - d ]咪唑-6-基）氨基甲酰基）苯甲酸酯（5a）和N-（2,2-difluoro-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）-3 -甲氧基苯甲酰胺（5c）及其相应的脱甲基前体3-（（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）氨基甲酰基）苯甲酸（6a）和N-（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）-3-羟基苯甲酰胺（6b）由5-氨基-2,2-二氟-1,3-苯并二恶唑和3-取代的苯甲酸分5步和6步合成，总化学收率分别为33％和11％，30％和7％。碳11标记的酪蛋白激酶1（CK1）抑制剂，[

  DOI：

  10.1016/j.bmcl.2018.05.053

文献信息

• BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS
  申请人：4SC DISCOVERY GMBH

  公开号：US20150158878A1

  公开（公告）日：2015-06-11

  The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof, wherein A, X, L, Y, R, and R N are as defined herein. The invention further relates to the use of the compounds of formula (I) as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.

  本发明涉及一种通式(I)的化合物或其生理功能衍生物、溶剂或盐，其中A、X、L、Y、R和RN如本文所定义。本发明还涉及将通式(I)的化合物用作药物，包括它们的制药组合物，以及治疗或预防需要其给药的医疗状况的方法，以及将其用于制造治疗或预防医疗状况的药物，尤其是自身免疫炎症性疾病、中枢神经系统疾病、睡眠障碍或增殖性疾病，包括癌症。本发明还涉及一种特定的制备上述化合物的方法。
• Difluoro-dioxolo-benzoimidazol-benzamides As Potent Inhibitors of CK1δ and ε with Nanomolar Inhibitory Activity on Cancer Cell Proliferation
  作者：Julia Richter、Joachim Bischof、Mirko Zaja、Hella Kohlhof、Olaf Othersen、Daniel Vitt、Vanessa Alscher、Irmgard Pospiech、Balbina García-Reyes、Sebastian Berg、Johann Leban、Uwe Knippschild

  DOI：10.1021/jm500600b

  日期：2014.10.9

  Deregulation of CK1 (casein kinase 1) activity can be involved in the development of several pathological disorders and diseases such as cancer. Therefore, research interest in identifying potent CK1 specifc inhibitors is still increasing. A previously published potent and selective benzimidazole-derived CK1 delta/epsilon specific inhibitor compound with significant effects on several tumor cell lines was further modified to difluoro-dioxolo-benzoimidazole derivatives displaying remarkable inhibitory effects and increased intracellular availability. In the present study, we identified two heterocyclic molecules as new CK-specific inhibitor compunds with favorable physicochemical properties and notable selectivity in a kinom-wide screen Being compared to other CK1 isoforms these compounds exhibited advanced isoform selectivity toward CK1 delta Moreover, newly designed compounds showed increased growth inhibitory activity in a panel of different tumor cell lines as determined by analyses of cell viability and cell cycle distribution. In summary presented lead optimization. resulted in new highly elective CK1 delta-specific small molecule inhibitors with increased biological activity.
• US9580438B2
  申请人：——

  公开号：US9580438B2

  公开（公告）日：2017-02-28
• Synthesis of carbon-11-labeled CK1 inhibitors as new potential PET radiotracers for imaging of Alzheimer’s disease
  作者：Mingzhang Gao、Min Wang、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2018.05.053

  日期：2018.7

  from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [11C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([11C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[11C]methoxybenzamide

  参考标准品甲基3-（（（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2 - d ]咪唑-6-基）氨基甲酰基）苯甲酸酯（5a）和N-（2,2-difluoro-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）-3 -甲氧基苯甲酰胺（5c）及其相应的脱甲基前体3-（（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）氨基甲酰基）苯甲酸（6a）和N-（2,2-二氟-5 H- [1,3] dioxolo [4'，5'：4,5]苯并[1,2- d ]咪唑-6-基）-3-羟基苯甲酰胺（6b）由5-氨基-2,2-二氟-1,3-苯并二恶唑和3-取代的苯甲酸分5步和6步合成，总化学收率分别为33％和11％，30％和7％。碳11标记的酪蛋白激酶1（CK1）抑制剂，[