Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

Journal Article (Journal Article)

A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55. The results of the assays were used to learn more about the binding pocket of GPR55. With this oxadiazolone scaffold, it was determined that modification of the aryl group adjacent to the oxadiazolone ring was often detrimental and that the distal cyclopropane was beneficial for activity. These results will guide further exploration of this receptor.

Full Text

Duke Authors

Cited Authors

  • Meza-Aviña, ME; Lingerfelt, MA; Console-Bram, LM; Gamage, TF; Sharir, H; Gettys, KE; Hurst, DP; Kotsikorou, E; Shore, DM; Caron, MG; Rao, N; Barak, LS; Abood, ME; Reggio, PH; Croatt, MP

Published Date

  • April 1, 2016

Published In

Volume / Issue

  • 26 / 7

Start / End Page

  • 1827 - 1830

PubMed ID

  • 26916440

Pubmed Central ID

  • PMC4836065

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2016.02.030


  • eng

Conference Location

  • England