Brebion, Franck published the artcileDiscovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis, HPLC of Formula: 180698-19-5, the publication is Journal of Medicinal Chemistry (2021), 64(6), 2937-2952, database is CAplus and MEDLINE.
There are currently no approved disease-modifying osteoarthritis (OA) drugs (DMOADs). The aggrecanase ADAMTS-5 is key in the degradation of human aggrecan (AGC), a component of cartilage. Therefore, ADAMTS-5 is a promising target for the identification of DMOADs. We describe the discovery of GLPG1972/S201086, a potent and selective ADAMTS-5 inhibitor obtained by optimization of a promising hydantoin series following an HTS. Biochem. activity against rat and human ADAMTS-5 was assessed via a fluorescence-based assay. ADAMTS-5 inhibitory activity was confirmed with human aggrecan using an AGC ELISA. The most promising compounds were selected based on reduction of glycosaminoglycan release after interleukin-1 stimulation in mouse cartilage explants and led to the discovery of GLPG1972/S201086. The anticatabolic activity was confirmed in mouse cartilage explants (IC50 < 1.5μM). The cocrystal structure of GLPG1972/S201086 with human recombinant ADAMTS-5 is discussed. GLPG1972/S201086 has been investigated in a phase 2 clin. study in patients with knee OA (NCT03595618).
Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, HPLC of Formula: 180698-19-5.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics