Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor

作者：Duncan C. Miller, Tristan D. Reuillon, Lauren Molyneux, Timothy J. Blackburn, Simon J. Cook, Noel Edwards, Jane Endicott, Bernard T. Golding, Roger J. Griffin, Ian Robert Hardcastle, Suzannah J. Harnor, Amy B. Heptinstall, Pamela A. Lochhead, Mathew P. Martin, Nick C. Martin, Stephanie M. Myers, David R. Newell, Richard A. Noble, Nicole Phillips, Laurent J. M. Rigoreau, Huw D. Thomas, Julie A. Tucker, Lan-Zhen Wang, Michael J. Waring, Ai-Ching Wong, Stephen R. Wedge, Martin E. M. Noble, Céline Cano · 发表于：Journal of Medicinal Chemistry · 年份：2022 · DOI：10.1021/acs.jmedchem.1c01756 · 被引用次数：7 · 研究领域：Melanoma and MAPK Pathways、Computational Drug Discovery Methods、Synthesis and biological activity

pharmacokinetic parameters led to the identification of a nonbasic pyrazole analogue with an optimal balance of ERK5 inhibition and oral exposure.