Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors

  • J Med Chem. 2013 Feb 28;56(4):1677-92. doi: 10.1021/jm301720p.
Fernando Padilla  1 ,  Niala Bhagirath ,  Shaoqing Chen ,  Eric Chiao ,  David M Goldstein ,  Johannes C Hermann ,  Jonathan Hsu ,  Joshua J Kennedy-Smith ,  Andreas Kuglstatter ,  Cheng Liao ,  Wenjian Liu ,  Lee E Lowrie Jr ,  Kin Chun Luk ,  Stephen M Lynch ,  John Menke ,  Linghao Niu ,  Timothy D Owens ,  Counde O-Yang ,  Aruna Railkar ,  Ryan C Schoenfeld ,  Michelle Slade ,  Sandra Steiner ,  Yun-Chou Tan ,  Armando G Villaseñor ,  Ce Wang ,  Jutta Wanner ,  Wenwei Xie ,  Daigen Xu ,  Xiaohu Zhang ,  Mingyan Zhou ,  Matthew C Lucas
Affiliations
  • 1. Hoffmann-La Roche Inc., pRED, Pharma Research & Early Development, 340 Kingsland Street, Nutley, New Jersey 07110, United States.
PMID: 23350847 DOI: 10.1021/jm301720p
Abstract

We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.