Lara Fakhouri1, Christopher D Cook1, Mohammed H Al-Huniti1, Linda M Console-Bram2, Dow P Hurst1, Michael B S Spano1, Daniel J Nasrallah1, Marc G Caron3, Larry S Barak3, Patricia H Reggio1, Mary E Abood2, Mitchell P Croatt4. 1. Department of Chemistry and Biochemistry, Natural Products and Drug Discovery Center, University of North Carolina at Greensboro, Greensboro, NC 27402, United States. 2. Temple University School of Medicine, Anatomy and Cell Biology, Center for Substance Abuse Research, 3420 North Broad St., Philadelphia, PA 19140, United States. 3. Duke Center of Excellence, 444 Sands Building, Department of Cell Biology, Durham, NC 27710, United States. 4. Department of Chemistry and Biochemistry, Natural Products and Drug Discovery Center, University of North Carolina at Greensboro, Greensboro, NC 27402, United States. Electronic address: mpcroatt@uncg.edu.
Abstract
GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information. The general route consisted of coupling a variety of p-aminophenyl sulfonamides to isothiocyanates to form acylthioureas. For the synthesis of a known naphthyl ethyl alcohol motif, route modification led to a shorter and more efficient process. The 22 analogues were analyzed for their ability to serve as agonists at GPR55 and valuable information for both ends of the molecule was ascertained.
GPR55, a n class="Gene">G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information. The general route consisted of coupling a variety of p-aminophenyl sulfonamides to isothiocyanates to form acylthioureas. For the synthesis of a known naphthyl ethyl alcohol motif, route modification led to a shorter and more efficient process. The 22 analogues were analyzed for their ability to serve as agonists at GPR55 and valuable information for both ends of the molecule was ascertained.
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