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Design, synthesis and biological evaluation of GPR55 agonists.

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.

SUBMITTER: Fakhouri L

PROVIDER: S-EPMC5752104 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of GPR55 agonists.

Fakhouri Lara L Cook Christopher D CD Al-Huniti Mohammed H MH Console-Bram Linda M LM Hurst Dow P DP Spano Michael B S MBS Nasrallah Daniel J DJ Caron Marc G MG Barak Larry S LS Reggio Patricia H PH Abood Mary E ME Croatt Mitchell P MP

Bioorganic & medicinal chemistry 20170613 16

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 sulfo ...[more]

PMID: 28673732

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