| Literature DB >> 26916440 |
Maria Elena Meza-Aviña1, Mary A Lingerfelt1, Linda M Console-Bram2, Thomas F Gamage2, Haleli Sharir2, Kristen E Gettys1, Dow P Hurst1, Evangelia Kotsikorou3, Derek M Shore1, Marc G Caron4, Narasinga Rao1, Larry S Barak4, Mary E Abood2, Patricia H Reggio1, Mitchell P Croatt1.
Abstract
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.Entities:
Keywords: Antagonist; Cancer; GPCR; GPR55; Neuropathic pain
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Year: 2016 PMID： 26916440 PMCID： PMC4836065 DOI： 10.1016/j.bmcl.2016.02.030
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823