RESUMO
High throughput screening of our compound library revealed a series of N-pyridyl-3-benzamides as low micromolar agonists of the human TRPV1 receptor. Synthesis of analogs in this series led to the discovery of a series of N-quinolin-3-yl-benzamides as low nanomolar antagonists of human TRPV1.
Assuntos
Benzamidas/síntese química , Benzamidas/farmacologia , Isoquinolinas/química , Piridinas/química , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Animais , Benzamidas/química , Benzamidas/uso terapêutico , Reagentes de Ligações Cruzadas/química , Humanos , Hiperalgesia/tratamento farmacológico , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.
Assuntos
Analgésicos , Benzamidas , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Analgésicos/síntese química , Analgésicos/química , Animais , Benzamidas/síntese química , Benzamidas/química , Camundongos , Estrutura Molecular , Medição da Dor/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The synthesis and structure-activity relationships of a novel series of aroylpyrrole alkylamides as potent selective bradykinin B(2) receptor antagonists are described. Several members of this series display nanomolar affinity at the B(2) receptor and show activity in an animal model of antinociception.
