Discovery of novel 1,2,3,4-tetrahydroisoquinolines and 3,4-dihydroisoquinoline-1(2H)-ones as potent and selective inhibitors of KDR: Synthesis, SAR, and pharmacokinetic properties

1,2,3,4-Tetrahydroisoquinolines and 3,4-dihydroisoquinoline-1(2H)-ones were identified as potent and selective inhibitors of KDR. The discovery, synthesis, and structure–activity relationships of these novel inhibitors are reported. In vitro metabolism and pharmacokinetic profiles of the most interesting compounds are discussed.

Graphical abstractThe synthesis, structure–activity relationships and pharmacokinetic properties of 1,2,3,4-tetrahydroisoquinolines (2) and 3,4-dihydroisoquinoline-1(2H)-ones (3), two novel classes of potent KDR inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide