Synthesis and antiproliferative activity of pyrrolo[2,3- b ]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety

摘要

Abstract A series of pyrrolo[2,3- b ]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety were synthesized, and evaluated for their antiproliferative activity against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine kinases (c-Met, Flt-3, PDGFR-β, VEGFR-2, EGFR, and c-Kit) inhibitory activities in?vitro . Most compounds showed moderate to excellent potency, with the most promising analogue 32 showing Flt-3/c-Met IC 50 value of 1.16/1.92?nM. Structure-activity relationship studies indicated that the hydrogen atom served as R 1 group was benefited to the potency, and mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring (such as R 3 ?=?4-F) showed a higher preference for antiproliferative activity. Graphical abstract A series of pyrrolo[2,3- b ]pyridine derivatives bearing 1,8-naphthyridin-2-one moiety ( 23 – 54 ) were designed, synthesized and evaluated for their activity against four cancer cell lines and six tyrosine kinases. The most promising compound 32 showed excellent activity in?vitro . Display Omitted Highlights ? A series of pyrrolo[2,3- b ]pyridine derivatives were designed and synthesized. ? The target compounds showed potent antitumor activity. ? Compound 32 showed an IC 50 value of 1.16/1.92?nM against Flt-3/c-Met kinase.