RESUMO
New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, quinazoline, 7-chloroquinoline, and 7-chloroquinazoline nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 4e-4g, and 4l are at least comparable to that of clinically used drugs flupirtine and tramadol under the same conditions.
Assuntos
Analgésicos/síntese química , Dor/fisiopatologia , Piperidinas/farmacologia , Piridinas/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Aminopiridinas/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Temperatura Alta , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Piperidinas/química , Piridinas/química , Quinazolinas/química , Tempo de Reação , Receptor 5-HT1B de Serotonina , Receptores de Serotonina/fisiologia , Receptores 5-HT1 de Serotonina , Relação Estrutura-Atividade , Tramadol/farmacologiaRESUMO
New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.
Assuntos
Analgésicos/farmacologia , Piperidinas/farmacologia , Piridinas/farmacologia , Pirrolidinas/farmacologia , Analgésicos/síntese química , Animais , Ligação Competitiva , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Medição da Dor/efeitos dos fármacos , Piperidinas/química , Ligação Proteica , Piridinas/química , Pirrolidinas/síntese química , Ratos , Receptores de Serotonina/metabolismoRESUMO
A series of epibatidine analogues and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Some of the compounds, especially those containing 8-azabicyclo[3.2.1]oct-2-ene moiety show high affinity for the nicotinic cholinergic receptor.
Assuntos
Analgésicos não Narcóticos/síntese química , Analgésicos não Narcóticos/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Agonistas Nicotínicos/síntese química , Agonistas Nicotínicos/metabolismo , Piridinas/síntese química , Piridinas/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Ligação Competitiva , Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Átrios do Coração/metabolismo , Concentração Inibidora 50 , Isomerismo , Cinética , Agonistas Nicotínicos/farmacologia , Piridinas/farmacologia , Ensaio Radioligante , Ratos , Receptor Muscarínico M1 , Receptor Muscarínico M2 , Receptor 5-HT1B de Serotonina , Receptores Muscarínicos/metabolismo , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de SerotoninaRESUMO
New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, isoquinoline, quinazoline, and phthalazine nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 7d, 8b, 8c, and 8e are at least comparable to that of the clinically used drugs flupirtine and tramadol under the same conditions.
Assuntos
Analgésicos/síntese química , Piperidinas/síntese química , Piridinas/síntese química , Analgésicos/farmacologia , Animais , Masculino , Camundongos , Piperidinas/farmacologia , Piridinas/farmacologia , RatosRESUMO
New deaza derivatives of anpirtoline have been synthesized by three different methods. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied.
