Brebion, Franck; Gosmini, Romain; Deprez, Pierre; Varin, Marie; Peixoto, Christophe; Alvey, Luke; Jary, Helene; Bienvenu, Natacha; Triballeau, Nicolas; Blanque, Roland; Cottereaux, Celine; Christophe, Thierry; Vandervoort, Nele; Mollat, Patrick; Touitou, Robert; Leonard, Philip; Ceuninck, Frederic De; Botez, Iuliana; Monjardet, Alain; van der Aar, Ellen; Amantini, David published an article in 2021. The article was titled 《Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis》, and you may find the article in Journal of Medicinal Chemistry.Electric Literature of C9H10O2 The information in the text is summarized as follows:
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). The results came from multiple reactions, including the reaction of 2-(Benzyloxy)acetaldehyde(cas: 60656-87-3Electric Literature of C9H10O2)
2-(Benzyloxy)acetaldehyde(cas: 60656-87-3) is a non-natural aldehyde. It undergoes enantioselective Mukaiyama aldol reaction with silylketene acetal nucleophiles in the presence of C2-symmetric bis(oxazolinyl)pyridine Cu(II) complex (catalyst).Electric Literature of C9H10O2
Referemce:
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Ether | (C2H5)2O – PubChem