RESUMO
Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound. Compound 8b demonstrated potent antinociceptive activity in vivo.
Assuntos
Amidas/química , Compostos Azabicíclicos/síntese química , Compostos Bicíclicos com Pontes/química , Indóis/síntese química , Piperazinas/química , Receptor CB1 de Canabinoide/agonistas , Animais , Compostos Azabicíclicos/química , Compostos Azabicíclicos/farmacologia , Desenho de Fármacos , Humanos , Indóis/química , Indóis/farmacologia , Camundongos , Microssomos Hepáticos/metabolismo , Piperazinas/síntese química , Piperazinas/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Relação Estrutura-AtividadeRESUMO
A novel series of alpha-amino-acid phenolic ester derivatives containing sulphide, sulphoxide, sulphone, ester and amide side chains were prepared and shown to display potent intravenous anaesthetic activity.
Assuntos
Aminoácidos/síntese química , Aminoácidos/farmacologia , Anestésicos Intravenosos/síntese química , Anestésicos Intravenosos/farmacologia , Fenóis/síntese química , Fenóis/farmacologia , Animais , Ésteres , Antagonistas de Receptores de GABA-A , Masculino , Camundongos , Equilíbrio Postural/efeitos dos fármacos , Propofol/farmacologia , Reflexo/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A number of water soluble bis-amino-2,6-dimethoxyphenyl ester derivatives were found to exhibit improved anaesthetic activity in mice relative to propofol 1. Of the analogues disclosed, 44 was further profiled in rodents and found to be a superior agent to propofol for the induction and maintenance of anaesthesia.