RESUMO
A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT(3) receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT(3)A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT(3) receptor antagonists with good metabolic stability. These novel analogues possess drug-like characteristics and have potential utility for the treatment of diseases attributable to improper 5-HT(3) receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D).
Assuntos
Benzoxazóis/química , Benzoxazóis/farmacologia , Descoberta de Drogas , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/química , Antagonistas da Serotonina/farmacologiaRESUMO
Three population monitoring methods were evaluated in support of a trap/vaccinate/release program for controlling a bat variant of rabies virus in skunks (Mephitis mephitis) in Flagstaff, Arizona (USA). Skunks were the primary species targeted for population monitoring during the program, but feral cats were also monitored as they represented an abundant secondary vector species capable of rabies transmission. Skunks were vaccinated and released, except for a subset tested for rabies. All captured cats were placed in the local animal shelter. Spotlight surveys essentially did not detect skunks, and were not able to detect reductions in the cat population. Catch-per-unit-effort marginally tracked population trends, but a passive track index adapted for an urban setting was most sensitive for detecting changes in skunk and cat populations. Mark-recapture population estimates could not be validly calculated from the data on captures and recaptures due to multiple violations of analytical assumptions.