Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor

Marie-Pierre Collin; Mario Lobell; Walter Hübsch; Dirk Brohm; Hartmut Schirok; Rolf Jautelat; Klemens Lustig; Ulf Bömer; Verena Vöhringer; Mélanie Héroult; Sylvia Grünewald; Holger Hess-Stumpp

doi:10.1002/cmdc.201700718

Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor

ChemMedChem. 2018 Mar 6;13(5):437-445. doi: 10.1002/cmdc.201700718. Epub 2018 Feb 16.

Authors

Affiliations

¹ Department of Medicinal Chemistry, Drug Discovery, Bayer AG, Postfach 101709, 42096, Wuppertal, Germany.
² Research Pharmacokinetics Group, Drug Discovery, Bayer AG, Germany.
³ Lead Discovery, Drug Discovery, Bayer AG, Germany.
⁴ Therapeutic Research Group, Oncology, Drug Discovery, Bayer AG, Germany.

PMID: 29451369
DOI: 10.1002/cmdc.201700718

Abstract

Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer. In this publication, we report its discovery by de novo structure-based design and medicinal chemistry optimization together with its pharmacokinetic profile.

Keywords: cancer; fibroblast growth factor receptor (FGFR); inhibitors; medicinal chemistry; structure-based design.

MeSH terms

Drug Discovery*
Humans
Models, Molecular
Molecular Structure
Piperazines / chemistry
Piperazines / pharmacology*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrroles / chemistry
Pyrroles / pharmacology*
Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors*
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Thiophenes / chemistry
Thiophenes / pharmacology*

Substances

Piperazines
Protein Kinase Inhibitors
Pyrroles
Small Molecule Libraries
Thiophenes
Rogaratinib
FGFR1 protein, human
Receptor, Fibroblast Growth Factor, Type 1