RESUMEN
New 1-[(2-acylamino)phenyl]-3, 4-dihydroisoquinolines were synthesized and tested for their acute toxicity and antitrichinosis activity. The above compounds were found to show their low toxicity and two compounds (G-1615 and G-1616) displayed a high antitrichinosis effect.
Asunto(s)
Antinematodos/química , Antinematodos/uso terapéutico , Isoquinolinas/química , Isoquinolinas/uso terapéutico , Trichinella spiralis , Triquinelosis/tratamiento farmacológico , Albendazol/uso terapéutico , Animales , Antinematodos/toxicidad , Evaluación Preclínica de Medicamentos , Isoquinolinas/toxicidad , RatonesRESUMEN
The paper describes the synthesis of the new agent G-1697 which is 4-[(benzo-2,1,3-thiadiazolyl-4)amino]-5, 6,7,8-tetrahydrobenzothieno [2,3-d] pyrimidine and the results of testing its acute toxicity and antiparasitic activity on a model of Echinococcus multilocularis invasion at the larval stage in cotton rats. The maximum nonlethal dose of G-1697 was 4.0 g/kg for outbred mice of both sexes whose weight was 14-16 g. Adult cotton rats (males) received the agent with their feed in increasing daily doses for 3 weeks continuously on days 8 to 28 after infection. The daily dose of its active ingredient varied from 0.03 to 0.35 g/kg and averaged 0.12 g/kg (the mean total dose per session was 2.47 g/kg). The baseline weight of parasitic larvocysts (PL) per animal averaged 0.28 g at the baseline. In the treated and control rats sacrificed 34 days following infection, the mean mass of PL per animal was 0.95 and 7.51 g, respectively. In the cotton rats treated with G-1697, the suppressed growth index calculated by three parameters (moderate, maximum, and minimum mass of PL in the animals of the comparable groups after treatment with regard to the similar baseline variables) was 90.8, 91.0 and 92.7, respectively, versus the controls. Among all PL found in each animal, its death was approximately 70-90% in the treated rats.
Asunto(s)
Anticestodos/síntesis química , Pirimidinas/síntesis química , Tiadiazoles/síntesis química , Animales , Anticestodos/uso terapéutico , Anticestodos/toxicidad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Equinococosis/tratamiento farmacológico , Equinococosis/parasitología , Echinococcus/efectos de los fármacos , Femenino , Larva/efectos de los fármacos , Masculino , Ratones , Pirimidinas/uso terapéutico , Pirimidinas/toxicidad , Sigmodontinae , Tiadiazoles/uso terapéutico , Tiadiazoles/toxicidad , Factores de TiempoRESUMEN
The study was undertaken to examine the fasciolacidal activity of the agents G-1411, G-1423, and G-1439. Tested, G-1439 was chosen for detailed investigations as a non-toxic fasciolacide.
Asunto(s)
Antiplatelmínticos/administración & dosificación , Benzamidas/administración & dosificación , Fascioliasis/tratamiento farmacológico , Fascioliasis/veterinaria , Enfermedades de las Ovejas/tratamiento farmacológico , Animales , Antiplatelmínticos/toxicidad , Benzamidas/toxicidad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/veterinaria , Ratones , OvinosRESUMEN
A procedure has been developed to manufacture the anthelminthic Triclonate. The agent was tested for the treatment of sheep's natural monieziasis infection and it was found to have a high activity.
Asunto(s)
Anticestodos/síntesis química , Anticestodos/uso terapéutico , Animales , Anticestodos/análisis , Anticestodos/toxicidad , Evaluación Preclínica de Medicamentos/veterinaria , Ratones , Monieziasis/tratamiento farmacológico , Niclosamida/uso terapéutico , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológico , Espectrofotometría Infrarroja , Tecnología FarmacéuticaAsunto(s)
Antihelmínticos/síntesis química , Benzamidas/síntesis química , Sulfonamidas/síntesis química , Tiadiazoles/síntesis química , Animales , Antihelmínticos/análisis , Antihelmínticos/uso terapéutico , Antihelmínticos/toxicidad , Benzamidas/análisis , Benzamidas/uso terapéutico , Benzamidas/toxicidad , Evaluación Preclínica de Medicamentos , Espectroscopía de Resonancia por Spin del Electrón , Ratones , Tamaño de la Partícula , Espectrofotometría Infrarroja , Relación Estructura-Actividad , Sulfonamidas/análisis , Sulfonamidas/uso terapéutico , Sulfonamidas/toxicidad , Tiadiazoles/análisis , Tiadiazoles/uso terapéutico , Tiadiazoles/toxicidad , Triquinelosis/tratamiento farmacológicoAsunto(s)
Anticestodos/síntesis química , Benzazepinas/síntesis química , Himenolepiasis/tratamiento farmacológico , Isoquinolinas/síntesis química , Animales , Anticestodos/uso terapéutico , Anticestodos/toxicidad , Benzazepinas/uso terapéutico , Benzazepinas/toxicidad , Evaluación Preclínica de Medicamentos , Isoquinolinas/uso terapéutico , Isoquinolinas/toxicidad , Ratones , Relación Estructura-ActividadRESUMEN
The paper describes the synthesis of 6-[4-alkylpiperazinyl-1)phenylamino]-1,2,5-thiadiazolo[3,4-h ]quinolines where methyl (Drug G-1574) and ethyl (Drug G-1569) are alkyls. The two agents are as effective as mebendazole against the larval stage of Echinococcus multilocularis infection. Drug G-1574 has been demonstrated to ensure 100% recovery of spontaneously Hymenolepis nana-infected albino mice given doses 2.5-5 times lower than the effective dose of phenasal (niclosamide).
Asunto(s)
Anticestodos/síntesis química , Anticestodos/uso terapéutico , Equinococosis/tratamiento farmacológico , Himenolepiasis/tratamiento farmacológico , Quinolinas/síntesis química , Quinolinas/uso terapéutico , Animales , Anticestodos/toxicidad , Evaluación Preclínica de Medicamentos , Equinococosis/parasitología , Femenino , Himenolepiasis/parasitología , Masculino , Mebendazol/uso terapéutico , Ratones , Niclosamida/uso terapéutico , Quinolinas/toxicidad , SigmodontinaeRESUMEN
Synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4-alkylpiperazinyl-1)phenylamine substitute. Only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. One of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named QUINOPRAZINE, showed some action against Plasmodium berghei chloroquine--resistant infection (isolate LN-K65). This agent was elected for further tests.
Asunto(s)
Antimaláricos/síntesis química , Compuestos Heterocíclicos/síntesis química , Quinolinas/síntesis química , Animales , Antimaláricos/uso terapéutico , Antimaláricos/toxicidad , Cloroquina/análogos & derivados , Cloroquina/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Compuestos Heterocíclicos/uso terapéutico , Compuestos Heterocíclicos/toxicidad , Malaria/tratamiento farmacológico , Masculino , Ratones , Plasmodium berghei , Quinolinas/uso terapéutico , Quinolinas/toxicidadRESUMEN
The results of preclinical trials of 28 new compounds of haloid-containing sulfamidobenzamides with low toxicity are presented. The trials on a hymenolepiasis model showed that effectiveness of N-(2,5-dichlorophenyl)-2/(3-nitro-4-chlorophenyl) sulfonylamino/-5-bromobenzamide was similar to that of the well-known drug niclosamide. In the trials on an opisthorchiasis model, 2 compounds were shown to be highly effective, and on a trichocephaliasis model 5 compounds showed a high activity.
Asunto(s)
Antihelmínticos/uso terapéutico , Benzamidas/uso terapéutico , Sulfonamidas/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Halógenos/uso terapéutico , Helmintiasis/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
The synthesis and the acute toxicity and anticestodal activity of l-alkyl-4-[-(heterylamino)phenyl]-piperazines are presented. These compounds were found to be able to suppress the growth of larvocysts of Echinococcus multilocularis in cotton rats when injected intraperitoneally in a single dose of 0.25 g/kg, close to capacity of mebendazole. The tested compounds were also highly effective against the adult stage of Hymenolepis nana. Experimentally infected mice given an oral single dose of 0.2-0.5 g/kg of the drug were radically cured.
Asunto(s)
Anticestodos/síntesis química , Equinococosis/tratamiento farmacológico , Himenolepiasis/tratamiento farmacológico , Piperazinas/síntesis química , Animales , Anticestodos/uso terapéutico , Anticestodos/toxicidad , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Ratones , Piperazinas/uso terapéutico , Piperazinas/toxicidad , SigmodontinaeRESUMEN
Anthelminthic properties of new series of haloid-containing benzamides have been studied. The anthelminthic activity-structure relationships of the compounds under study has been examined. A number of highly active compounds promising for further investigations have been identified.
Asunto(s)
Antihelmínticos/uso terapéutico , Benzamidas/uso terapéutico , Animales , Cricetinae , Evaluación Preclínica de Medicamentos , Equinococosis/tratamiento farmacológico , Himenolepiasis/tratamiento farmacológico , Mesocricetus , Ratones , Opistorquiasis/tratamiento farmacológico , Sigmodontinae , Relación Estructura-ActividadAsunto(s)
Antihelmínticos/síntesis química , Benzamidas/síntesis química , Animales , Antihelmínticos/toxicidad , Benzamidas/toxicidad , Benzofenonas/síntesis química , Benzofenonas/toxicidad , Femenino , Masculino , Ratones , Relación Estructura-Actividad , Sulfonas/síntesis química , Sulfonas/toxicidadRESUMEN
Antimalarial activity of 10 N-(haloidnaphthyloxy)-2-hydroxy-3,5-dihaloidbenzamide compounds earlier synthesized as potential anthelmintics has been studied. It has been shown that antimalarial activity is typical only of amides of 2-hydroxy-3,5-diiodinebenzoic acid.
Asunto(s)
Antimaláricos/uso terapéutico , Benzamidas/uso terapéutico , Malaria/tratamiento farmacológico , Plasmodium berghei , Animales , Antimaláricos/toxicidad , Benzamidas/toxicidad , Cloroquina/análogos & derivados , Cloroquina/uso terapéutico , Evaluación Preclínica de Medicamentos , RatonesRESUMEN
Sulfamidobenzamides containing benzo-2,1,3-thiadiazole ring in the sulfamide group were synthesized and examined for acute toxicity. All the compounds were shown to have low toxicity (when administered orally in a dose of 4 g/kg to mice), the above fact makes possible the search for agents with anthelminthic activity.
Asunto(s)
Antihelmínticos/síntesis química , Benzamidas/síntesis química , Sulfonamidas/síntesis química , Animales , Antihelmínticos/toxicidad , Benzamidas/toxicidad , Femenino , Dosificación Letal Mediana , Masculino , Ratones , Relación Estructura-Actividad , Sulfonamidas/toxicidadRESUMEN
Novel derivatives of sulfamidobenzamides have been synthesized and tested for acute toxicity. All the compounds were shown to possess a low toxicity. It was suggested that the investigated sulfamidobenzamides might be a promising group among which to search for agents having anthelminthic activity.
Asunto(s)
Antihelmínticos/síntesis química , Sulfonamidas/síntesis química , Animales , Antihelmínticos/química , Antihelmínticos/toxicidad , Fenómenos Químicos , Química Física , Femenino , Masculino , Ratones , Sulfonamidas/química , Sulfonamidas/toxicidadRESUMEN
The paper presents the results of toxicological study of 44 compounds of the benzamide series synthesized during search for new anthelminthic agents. The dependence of the toxic effect of the benzamides synthesized on their structure is analysed. The experiments were carried out on white mice given the compounds under study once orally. The maximum tolerated doses of the compounds are presented. It has been found that 34 out of 44 compounds have a low toxicity and are worth of further anthelminthic screening.