Design, synthesis and SAR analysis of novel potent and selective small molecule antagonists of NPBWR1 (GPR7).

Design, synthesis and SAR analysis of the 5-chloro-4-(4-methoxyphenoxy)-2-(p-toly)pyridazin-3(2H)-one hit, identified through high-through-put screening (HTS) of the Molecular Libraries-Small Molecule Repository, led to the discovery of novel small molecule antagonists of NPBWR1 (GPR7). The lead molecule 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one 1z (CYM50557) display submicromolar antagonist activity at the target receptor and high selectivity against a panel of therapeutically relevant off-targets. 1z may provide a pharmacological tool to probe the molecular basis of the in vivo physiological function and therapeutic utility of the target receptor in diverse disease areas including inflammatory pain and eating disorders.