Design, synthesis and biological evaluation of GPR55 agonists

Publication date: 15 August 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 16
Author(s): Lara Fakhouri, Christopher D. Cook, Mohammed H. Al-Huniti, Linda M. Console-Bram, Dow P. Hurst, Michael B.S. Spano, Daniel J. Nasrallah, Marc G. Caron, Larry S. Barak, Patricia H. Reggio, Mary E. Abood, Mitchell P. Croatt
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.

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