Harris, Philip A. published the artcileDiscovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1247-1261, database is CAplus and MEDLINE.
RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-mol. inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, the authors report the lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clin. candidate GSK2982772 (compound I), currently in phase 2a clin. studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound I potently binds to RIP1 with exquisite kinase specificity and 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. The highly favorable physicochem. and ADMET properties of I, combined with high potency, led to a predicted low oral dose in humans.
Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Name: (1H-Pyrazol-5-yl)boronic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics