N-(5-amino-2-(tert-butyl)-11-fluorobenzo[f]thiazolo[4,5-h]-quinazolin-10-yl)-2,6-difluorobenzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并噻唑类
• 英文名称: N-(5-amino-2-(tert-butyl)-11-fluorobenzo[f]thiazolo[4,5-h]-quinazolin-10-yl)-2,6-difluorobenzenesulfonamide
• 英文别名: dabrafenib_photo；N-(9-amino-4-tert-butyl-17-fluoro-5-thia-3,8,10-triazatetracyclo[11.4.0.02,6.07,12]heptadeca-1(13),2(6),3,7,9,11,14,16-octaen-16-yl)-2,6-difluorobenzenesulfonamide
• 化学式: C₂₃H₁₈F₃N₅O₂S₂
• 分子量: 517.555
• InChiKey: ALICQCBMYRIXHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  达帕菲尼 以 四氢呋喃 为溶剂， 反应 0.6h， 以37%的产率得到N-(5-amino-2-(tert-butyl)-11-fluorobenzo[f]thiazolo[4,5-h]-quinazolin-10-yl)-2,6-difluorobenzenesulfonamide
  参考文献：
  名称：

  Photoinduced Conversion of Antimelanoma Agent Dabrafenib to a Novel Fluorescent BRAF^V600E Inhibitor

  摘要：

  Dabrafenib (Tafinlar) was approved in 2013 by the FDA as a selective single agent treatment for patients with BRAF(V600E) mutation-positive advanced melanoma. One year later, a combination of dabrafenib and trametinib was used for treatment of BRAF(V600E/K) mutant metastatic melanoma. In the present study, we report on hitherto not described photosensitivity of dabrafenib both in organic and aqueous media. The half-lives for dabrafenib degradation were determined. Moreover, we revealed photoinduced chemical conversion of dabrafenib to its planar fluorescent derivative dabrafenib_photo 2. This novel compound could be isolated and biologically characterized in vitro. Both enzymatic and cellular assays proved that 2 is still a potent BRAF(V600E) inhibitor. The intracellular formation of 2 from dabrafenib upon ultraviolet irradiation is shown. The herein presented findings should be taken in account when handling dabrafenib both in preclinical research and in clinical applications.

  DOI：

  10.1021/acsmedchemlett.6b00340

文献信息

• Photoinduced Conversion of Antimelanoma Agent Dabrafenib to a Novel Fluorescent BRAF^V600E Inhibitor
  作者：Boris Pinchuk、Thorsten von Drathen、Viktoria Opel、Christian Peifer

  DOI：10.1021/acsmedchemlett.6b00340

  日期：2016.10.13

  Dabrafenib (Tafinlar) was approved in 2013 by the FDA as a selective single agent treatment for patients with BRAF(V600E) mutation-positive advanced melanoma. One year later, a combination of dabrafenib and trametinib was used for treatment of BRAF(V600E/K) mutant metastatic melanoma. In the present study, we report on hitherto not described photosensitivity of dabrafenib both in organic and aqueous media. The half-lives for dabrafenib degradation were determined. Moreover, we revealed photoinduced chemical conversion of dabrafenib to its planar fluorescent derivative dabrafenib_photo 2. This novel compound could be isolated and biologically characterized in vitro. Both enzymatic and cellular assays proved that 2 is still a potent BRAF(V600E) inhibitor. The intracellular formation of 2 from dabrafenib upon ultraviolet irradiation is shown. The herein presented findings should be taken in account when handling dabrafenib both in preclinical research and in clinical applications.