Details

Autor(en) / Beteiligte

• Li, Bo
• Wang, Gaihong
• Xu, Zhijian
• Zhang, Yong
• Huang, Xiangui
• Zeng, Bubing
• Chen, Kaixian
• Shi, Jiye
• Wang, Heyao
• Zhu, Weiliang

Titel

Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement

Ist Teil von

• European journal of medicinal chemistry, 2014-04, Vol.77, p.204-210

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• The present study discovers multiple N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement. The current [2,3] rearrangement of epoxy or acetal O-substituents converting to diol or alcohol N-substituents can be promoted by silica gel or by diluted hydrochloric acid, which is distinct from previously reported [2,3] rearrangements. Some of the derivatives displayed comparable or even stronger cytotoxicity than sorafenib and vemurafenib on HCT116 colon carcinoma and A375 melanoma cell lines. Therefore, the rearrangement via intramolecular carbon-oxygen bond cleavage and carbon-nitrogen bond formation should be a useful approach for developing novel anticancer drugs derived from isoquinolones. Several N-substituted isoquinolones were obtained via [2,3] or [3,3] rearrangement, among which, 4h and 4j showed strong antitumor activities close to vemurafenib and sorafenib. [Display omitted] •Several N-substituted isoquinolones were obtained via [2,3] or [3,3] rearrangement.•4h and 4j showed strong antitumor activities close to vemurafenib and sorafenib.•The unusual [2,3] rearrangement is a novel rearrangement observed on lactams.