Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues

A novel series of thiazolo[2,3-b]quinazoline (14–23, 26 and 27), and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine (34–43, 45 and 46) analogues were designed and synthesized. The obtained compounds were evaluated for their in-vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 22, 38, 40 and 41 showed remarkable broad-spectrum antitumor activity. Compounds 22 and 38 are almost nine fold more active than 5-FU, with GI50, TGI, and LC50 values of 2.5, >100, >100; and 2.4, 9.1, 36.2 μM, respectively; while 40 and 41 are almost seven fold more active than 5-FU, with GI50, TGI, and LC50 values of 2.9, 12.4, 46.6 and 3.0, 16.3, 54.0 μM, respectively.

Compounds 22 and 38 are almost nine fold, while 40 and 41 are almost seven fold, more active than the known antitumor 5-FU.Figure optionsDownload as PowerPoint slideHighlights
► Thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were synthesized.
► In-vitro antitumor activity of the new compounds was evaluated.
► Compounds 22 and 38 are almost nine fold more active than 5-FU.
► Compounds 40 and 41 are almost seven fold more active than 5-FU.