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

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 ca...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2014-04, Vol.77, p.204-210
Main Authors: Li, Bo, Wang, Gaihong, Xu, Zhijian, Zhang, Yong, Huang, Xiangui, Zeng, Bubing, Chen, Kaixian, Shi, Jiye, Wang, Heyao, Zhu, Weiliang
Format: Article
Language:English
Subjects:
3-Arylisoquinolone
[2,3] rearrangement
[3,3] rearrangement
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antitumor
Cell Line, Tumor
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Isoquinolines - chemical synthesis
Isoquinolines - chemistry
Isoquinolines - pharmacology
Molecular Structure
Structure-Activity Relationship
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2014.03.008