Design, Synthesis, and Pharmacological Evaluation of Novel Quinolone Aryl Sulfonamide Derivatives as Potent GPR55 Antagonists
Paula Morales,
Laura Figuerola-Asencio,
Dow H. Hurst,
Pingwei Zhao,
Mary E. Abood,
Patricia H. Reggio,
Nadine Jagerovic
Affiliations
Paula Morales
Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain
Laura Figuerola-Asencio
Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain
Dow H. Hurst
Department of Chemistry and Biochemistry, UNC Greensboro, Greensboro, NC 27402, USA
Pingwei Zhao
Center for Substance Abuse Research, Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Mary E. Abood
Center for Substance Abuse Research, Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Patricia H. Reggio
Department of Chemistry and Biochemistry, UNC Greensboro, Greensboro, NC 27402, USA
Nadine Jagerovic
Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain
Docking studies of identified GPR55 ligands using a GPR55 inactive state model allow rationalizing key structural features involved in ligand–receptor binding. On this molecular basis, we have designed novel quinolone sulfonamide derivatives with optimized potency and efficacy. These novel molecules compounds are being synthesized and evaluated using a β-arrestin recruitment assay in CHO cells overexpressing human GPR55 and βarr2-GFP.
