RESUMEN
Ten novel alpha and beta class milbemycins have been isolated and characterized from the Streptomyces sp. E225, which has previously been shown to produce four related milbemycins. Some of the metabolites contain new structural features including, VM48641 which possesses an alpha-methoxyl substituent at C-27, and VM48642 which contains a furan ring at the terminus of the C-26 side chain. Several of these new compounds were shown to possess potent anthelmintic activity. An analysis of NMR chemical shift trends in this series of metabolites is presented.
Asunto(s)
Antihelmínticos/metabolismo , Antibacterianos/biosíntesis , Streptomyces/metabolismo , Animales , Antihelmínticos/química , Antihelmínticos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Fenómenos Químicos , Química Física , Cromatografía Líquida de Alta Presión , Fermentación , Haemonchus/efectos de los fármacos , Macrólidos/química , Macrólidos/metabolismo , Macrólidos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Trichostrongylus/efectos de los fármacosRESUMEN
A novel series of milbemycin antibiotics were isolated from the fermentation broth of a Streptomyces species designated E225. The structures of the four main metabolites VM 44857 (1), VM 44864 (2), VM 44865 (3) and VM 44866 (4) were determined by NMR techniques. In addition we describe the solution conformations of the major metabolite VM 44857 (1).
Asunto(s)
Antihelmínticos/aislamiento & purificación , Antibacterianos/aislamiento & purificación , Streptomyces/metabolismo , Animales , Antihelmínticos/química , Antibacterianos/química , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Macrólidos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estructura MolecularRESUMEN
A series of 1,2,3,4,6,7,8,12b-octahydropyrazino[2,1-alpha][2] benzazepine derivatives was prepared and the cestocidal activity of the compounds evaluated in an in vitro Taenia crassiceps screen. Many of these derivatives proved to be highly active, and 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b- octahydropyrazino[2,1-alpha][2]benzazepine, epsiprantel (BAN) (22), was selected for further development. The structure-activity relationships are discussed.
Asunto(s)
Anticestodos/síntesis química , Benzazepinas/síntesis química , Animales , Anticestodos/farmacología , Anticestodos/uso terapéutico , Benzazepinas/farmacología , Benzazepinas/uso terapéutico , Fenómenos Químicos , Química , Perros , Isomerismo , Relación Estructura-Actividad , Taenia/efectos de los fármacos , Teniasis/tratamiento farmacológicoRESUMEN
A series of isothiourea derivatives of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (tetramisole) is described. The compounds are prepared by the S-alkylation of the thioureas that were obtained either by the reaction of an amine with 6-(3-isothiocyanatophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b] thiazole or by the reaction of an isothiocyanate with 6-(3-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole. These derivatives have an improved spectrum of activity over tetramisole and are active against nematodes, cestodes, and trematodes. The structure-activity relationships are discussed.