3-Amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile

doi:10.1016/j.bmcl.2008.12.044

Bioorganic & Medicinal Chemistry Letters

Volume 19, Issue 3, 1 February 2009, Pages 701-705

https://doi.org/10.1016/j.bmcl.2008.12.044 Get rights and content

Abstract

The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified.

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Acknowledgments

The authors thank our colleagues Minwei Ye, Galina Repik and Tony Cheung for biological data, Dominique Custeau for PK studies, and Michael Block and Paul Lyne for assistance with the manuscript.

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