RESUMO
A series of benzamides was synthesized as selective agonists for the 5-HT1A receptor. It was found that (S)-N-[[1-(2-phenylethyl)pyrrolidin-2-yl]methyl]cyclohexanecarb oxamide(7-(S)) has potent and selective agonistic activity for the 5-HT1A receptor (5-HT1A; Ki 0.49 nmol/L, D2; IC50 = >1000 nmol/L, 5-HT2; Ki = 240 nmol/L).
Assuntos
Amidas/síntese química , Pirrolidinas/síntese química , Receptores de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/síntese química , Amidas/farmacologia , Animais , Ligação Competitiva/efeitos dos fármacos , Técnicas In Vitro , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pirrolidinas/farmacologia , Núcleos da Rafe/citologia , Núcleos da Rafe/efeitos dos fármacos , Núcleos da Rafe/metabolismo , Ratos , Receptor 5-HT2A de Serotonina , Receptores de Dopamina D2/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT(4) receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT(4) receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT(4) receptors than the other receptors, including, 5-HT(3) and dopamine D(2) receptors. In addition, compound 24 was confirmed to be a potent 5-HT(4) receptor agonist (ED(50) = 7.0 nM). An interaction model between compound 24 and 5-HT(4) receptor was proposed.
RESUMO
Griseofulvin derivatives, dl-6'-demethyl-6'-ethylgriseofulvin (dl-5) and dl-6'demethyl-6'phenylgriseofulvin (dl-6) were prepared by application of a synthetic method developed by us. Antifungal activity of these derivatives decreased in the order of dl-griseofulvin (dl-1) >> dl-6(inactive). The reaction of these derivatives with ethanethiol gave two types of compounds, 2'-(ethylthio)griseofulvin (15) and 4'-(ethylthio)isogriseofulvin (16). The relationship between the ratios of isolated yield of 15 and 16 and antifungal the activity of griseofulvin derivatives is discussed.
Assuntos
Antifúngicos/síntese química , Griseofulvina/análogos & derivados , Antifúngicos/farmacologia , Griseofulvina/síntese química , Griseofulvina/química , Griseofulvina/farmacologia , Testes de Sensibilidade Microbiana , Trichophyton/efeitos dos fármacosRESUMO
dl-Griseofulvin (1a) was prepared by two synthetic pathways. New 6'-congeners (3 and 4) of griseofulvin were also prepared. Their antifungal activities were evaluated and compounds 3 and 4 were found to be less active than 1a. Molecular calculations on 1a, dl-epigriseofulvin (1b), 3 and 4 were undertaken.