Design, synthesis, and in vitro/vivo anticancer activity of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines

Abstract

AbstractIn this paper, we report the design and synthesis of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines of scaffold 6 as anticancer agents. A total of 19 derivatives of scaffold 6 bearing a C‐4 alkoxy, dialkylamino, alkyl, vinyl, or phenyl substituent were synthesized and evaluated. Among them, compound 6q having a C‐4 ethyl group and a benzylic methyl group showed the most potent in vitro anticancer activity, inhibiting the proliferation of Hela, MDA‐MB‐231, and MDA‐MB‐426 cancer cells at submicromolar concentrations (GI50: 0.11–0.58 μM). Compound 6q arrested the cell cycle of MDA‐MB‐231 at G2/M phase, and showed in vivo activity on nude mice bearing MDA‐MB‐231 xenografts. Compound 6q has served as an anticancer lead for further optimization.