Document Report Card
Basic Information
ID: ALA4823291
Journal: Bioorg Med Chem Lett
Title: Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine derivatives as novel selective Axl inhibitors.
Authors: Inoue S, Yamane Y, Tsukamoto S, Murai N, Azuma H, Nagao S, Nishibata K, Fukushima S, Ichikawa K, Nakagawa T, Hata Sugi N, Ito D, Kato Y, Goto A, Kakiuchi D, Ueno T, Matsui J, Matsushima T.
Abstract: Axl and Mer are members of the TAM (Tyro3-Axl-Mer) family of receptor tyrosine kinases. Previously, we reported that enzyme-mediated inhibition of Mer by an Axl/Mer dual inhibitor led to retinal toxicity in mice, whereas selective Axl inhibition by compound 1 did not. On the other hand, compound 1 showed low membrane permeability. Here, we designed and synthesized a novel series of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine derivatives and evaluated their Axl and Mer inhibitory activities, leading to identification of ER-001259851-000 as a potent and selective Axl inhibitor with drug-likeness and a promising pharmacokinetic profile in mice.
CiteXplore: 34271070