6ivx

Publication Abstract from PubMed

Starting from a previously reported RORgamma inhibitor (1), successive efforts to improve in vivo potency were continued. Introduction of metabolically beneficial motifs in conjunction with scaffold hopping was examined, resulting in discovery of the second generation RORgamma inhibitor composed of a 4-(isoxazol-3-yl)butanoic acid scaffold (24). Compound 24 achieved a 10-fold improvement in in vivo potency in a mouse CD3 challenge model along with significant anti-inflammatory effects in a mouse dermatitis model.

Discovery of Second Generation RORgamma Inhibitors Composed of an Azole Scaffold.,Kotoku M, Maeba T, Fujioka S, Yokota M, Seki N, Ito K, Suwa Y, Ikenogami T, Hirata K, Hase Y, Katsuda Y, Miyagawa N, Arita K, Asahina K, Noguchi M, Nomura A, Doi S, Adachi T, Crowe P, Tao H, Thacher S, Hashimoto H, Suzuki T, Shiozaki M J Med Chem. 2019 Mar 1. doi: 10.1021/acs.jmedchem.8b01567. PMID:30776227^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.