RESUMO
A series of 3-amino-6-aryl-pyridazines have been identified as CB(2) agonists with high efficacy and selectivity against the CB(1) receptor. Details of the investigation of structure-activity relationships (SAR) are disclosed, which led to the identification of pyridazine analogue 35, a compound with high potency in an in vivo model of inflammatory pain.
Assuntos
Anti-Inflamatórios/síntese química , Isoquinolinas/síntese química , Piridazinas/síntese química , Receptor CB2 de Canabinoide/agonistas , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Isoquinolinas/química , Isoquinolinas/farmacocinética , Dor/tratamento farmacológico , Piridazinas/química , Piridazinas/farmacocinética , Ratos , Receptor CB2 de Canabinoide/metabolismo , Relação Estrutura-AtividadeRESUMO
2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a synthetically tractable series of CB(2) agonists from a high-throughput screen of the GlaxoSmithKline compound collection. Described herein are the results of an investigation of the structure-activity relationships (SAR) which led to the identification a number of potent and selective agonists.
Assuntos
Piridinas/síntese química , Piridinas/farmacologia , Receptor CB2 de Canabinoide/agonistas , Desenho de Fármacos , Estrutura Molecular , Piridinas/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
The novel 7-transmembrane receptor MrgX1 is located predominantly in the dorsal root ganglion and has consequently been implicated in the perception of pain. Here we describe the discovery and optimization of a small molecule agonist and initial docking studies of this ligand into the receptor in order to provide a suitable lead and tool compound for the elucidation of the physiological function of the receptor.