N-methylthioureas as new agonists of retinoic acid receptor-related orphan receptor

Abstract

Thirty two thiourea derivatives were prepared and their agonistic activities on the retinoic acid receptor-related orphan receptor alpha (ROR alpha) were evaluated. The replacement of the 3-allyl-2-imino-thiazolidin-4-one moiety of the lead compound CGP52608 (1) with various functional group substituted aromatic rings, improved the agonistic activity of ROR alpha. Among the prepared derivatives, 1-methyl-3-(4-phenoxy-benzyl)-thiourea (32) showed 2.6-fold higher agonistic activity than CGP52608 in the ROR alpha-activation assay.