Asunto(s)
Antraquinonas/toxicidad , Animales , Antraquinonas/síntesis química , Antraquinonas/química , Antraquinonas/farmacología , Pruebas de Carcinogenicidad , Carcinógenos/síntesis química , Carcinógenos/química , Carcinógenos/farmacología , Carcinógenos/toxicidad , Catárticos/síntesis química , Catárticos/química , Catárticos/farmacología , Catárticos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/legislación & jurisprudencia , Guías como Asunto , Humanos , Masculino , Ratones , Modelos Biológicos , RatasRESUMEN
The syntheses and biological evaluation of a series of novel indeno[1,2-d]thiazole derivatives are described. Several groups reported 5-HT(3) receptor agonists which were mainly evaluated for their activities on the von Bezold-Jarisch reflex (B-J reflex). We discovered that tetrahydrothiazolopyridine derivative 1b had a contractile effect on the isolated guinea pig colon with weak B-J reflex. Our efforts to find a new type of 5-HT(3) receptor agonists on the isolated guinea pig colon focused on the synthesis of a fused thiazole derivative 1d modified from 1b and reverse-fused thiazole derivatives (7-10). In this series, 10f (YM-31636) showed high affinity and selectivity for the cloned human 5-HT(3) receptor; furthermore, it showed potent and selective 5-HT(3) receptor agonistic activity. YM-31636 was examined for its effects on defecation in animals, thus evaluating the compound as an agent against constipation.