GSK2982772

Description

(S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, also known as GSK2982772, is a first-in-class receptor interacting protein 1(RIP1)-kinase specific clinical candidate for the treatment of inflammatory disease. It is an inhibitor of RIP1 that regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. It has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants.

References

Harris, P. A., et al. "Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases." Journal of Medicinal Chemistry 60.4(2017):1247-1261.
Jeong, Jae Uk, et al. "Synthesis of ( S )-3-amino-benzo[ b ][1,4]oxazepin-4-one via Mitsunobu and S N Ar reaction for a first-in-class RIP1 kinase inhibitor GSK2982772 in clinical trials." Tetrahedron Letters 58.23(2017):2306-2308.