Thienopyridine and benzofuran derivatives as potent anti-tumor agents possessing different structure-activity relationships.
(3-Amino-6-thiophen-2-yl-thieno[2,3-b]pyridin-2-yl)phenylmethanone (3) was discovered as a new type of cytotoxic agent selective against a tumorigenic cell line. The molecular structure of a previously reported compound, (4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)phenylmethanone (2), had remarkably similar bioisosteric substructures to that of compound 3. Although the relationship between the molecular structure and biological activity of each derivative synthesized from these two hit compounds (2 and 3) were studied, unexpectedly no correlation was observed. However, after further synthetic study from 3, one of the most potent derivative (10k) having a different SAR profile from 2, was discovered.
Hayakawa
Ichiro
I
Lead Discovery Research Laboratories, Sankyo Co. Ltd, Shinagawa-ku, Tokyo 140-8710, Japan.
Shioya
Rieko
R
Agatsuma
Toshinori
T
Furukawa
Hidehiko
H
Sugano
Yuichi
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001572:Benzofurans; D011725:Pyridines; C446540:thienopyridine