2. Academic Validation
  3. Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis

Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6258-63. doi: 10.1016/j.bmcl.2011.09.008.
Kyung-Hee Kim 1,  Andreas Maderna,  Mark E Schnute,  Martin Hegen,  Shashi Mohan,  Joy Miyashiro,  Laura Lin,  Evelyn Li,  Sean Keegan,  Jennifer Lussier,  Christopher Wrocklage,  Cheryl L Nickerson-Nutter,  Arthur J Wittwer,  Holly Soutter,  Nicole Caspers,  Seungil Han,  Ravi Kurumbail,  Kyri Dunussi-Joannopoulos,  John Douhan 3rd,  Allan Wissner
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Pfizer, 200 Cambridge Park Drive, Cambridge, MA 02140, United States. khkim87@hotmail.com
PMID: 21958547 DOI: 10.1016/j.bmcl.2011.09.008
Abstract

Imidazo[1,5-a]quinoxalines were synthesized that function as irreversible Bruton's tyrosine kinase (Btk) inhibitors. The syntheses and SAR of this series of compounds are presented as well as the X-ray crystal structure of the lead compound 36 in complex with a gate-keeper variant of ITK Enzyme. The lead compound showed good in vivo efficacy in preclinical RA models.

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