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

Arch Pharm Res. 2012 Aug;35(8):1393-401. doi: 10.1007/s12272-012-0809-0. Epub 2012 Sep 1.

Abstract

Thirty two thiourea derivatives were prepared and their agonistic activities on the retinoic acid receptor-related orphan receptor α (RORα) 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 RORα. Among the prepared derivatives, 1-methyl-3-(4-phenoxy-benzyl)-thiourea (32) showed 2.6-fold higher agonistic activity than CGP52608 in the RORα-activation assay.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hep G2 Cells
  • Humans
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / agonists*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology*
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis
  • Thiourea / chemistry
  • Thiourea / pharmacology

Substances

  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • RORA protein, human
  • Thiazoles
  • Thiosemicarbazones
  • N-methylthiourea
  • CGP 52608
  • Thiourea