Subject(s)
Anthelmintics/adverse effects , Anthelmintics/therapeutic use , Benzamides/adverse effects , Benzamides/therapeutic use , Naphthalenes/adverse effects , Naphthalenes/therapeutic use , Administration, Oral , Animals , Anthelmintics/chemistry , Anthelmintics/isolation & purification , Benzamides/chemistry , Benzamides/isolation & purification , Drug Evaluation, Preclinical , Hymenolepiasis/drug therapy , Hymenolepis nana , Mice , Naphthalenes/chemistry , Naphthalenes/isolation & purificationSubject(s)
Anthelmintics/therapeutic use , Benzamides/therapeutic use , Hymenolepiasis/drug therapy , Hymenolepis nana , Thiadiazoles/therapeutic use , Administration, Oral , Animals , Anthelmintics/toxicity , Benzamides/chemistry , Benzamides/toxicity , Drug Evaluation, Preclinical , Mice , Molecular Structure , Structure-Activity Relationship , Thiadiazoles/chemistry , Thiadiazoles/toxicityABSTRACT
The papers describes the synthesis of N-(2-piperidinoethyl)-N-tosyl-n-anisidine (Tanfelam) which showed a 100% ovicidal activity when tested by the Harada and Mori methods (in vitro inhibited N.brasiliensis hatching and development test). Tanfelam has been transferred for in-depth tests.
Subject(s)
Life Cycle Stages/drug effects , Nippostrongylus/growth & development , Ovum/drug effects , Piperidines/chemical synthesis , Piperidines/pharmacology , Tosyl Compounds/chemical synthesis , Tosyl Compounds/pharmacology , Animals , Animals, Outbred Strains , Dose-Response Relationship, Drug , Female , Larva/drug effects , Lethal Dose 50 , Male , Mice , Molecular Structure , Nippostrongylus/drug effects , Piperidines/chemistry , Piperidines/toxicity , Time Factors , Tosyl Compounds/chemistry , Tosyl Compounds/toxicity , Toxicity Tests, AcuteABSTRACT
The paper describes a procedure for manufacturing the new anthelminthic Tizanox. It shows it necessary to administer a larger dose of the drug than that of azinox (praziquantel) to treat experimental hymenolepiasis. However, the lower toxicity of Tizanox enhances its chemotherapeutical index.
Subject(s)
Anticestodal Agents/chemical synthesis , Anticestodal Agents/therapeutic use , Hymenolepiasis/drug therapy , Isoquinolines/chemical synthesis , Isoquinolines/therapeutic use , Thiadiazines/chemical synthesis , Thiadiazines/therapeutic use , Animals , Anticestodal Agents/analysis , Anticestodal Agents/toxicity , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Isoquinolines/analysis , Isoquinolines/toxicity , Mice , Praziquantel/analogs & derivatives , Praziquantel/therapeutic use , Praziquantel/toxicity , Spectrophotometry, Infrared/statistics & numerical data , Thiadiazines/analysis , Thiadiazines/toxicityABSTRACT
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.
Subject(s)
Antinematodal Agents/chemistry , Antinematodal Agents/therapeutic use , Isoquinolines/chemistry , Isoquinolines/therapeutic use , Trichinella spiralis , Trichinellosis/drug therapy , Albendazole/therapeutic use , Animals , Antinematodal Agents/toxicity , Drug Evaluation, Preclinical , Isoquinolines/toxicity , MiceABSTRACT
A procedure was developed for the synthesis of the anthelminthic G-1460. The therapeutical doses (20 and 25 mg/kg) of the agent were defined for the treatment of monieziasis and gastrointestinal nematodes on an individual basis.
Subject(s)
Anticestodal Agents/chemical synthesis , Antinematodal Agents/chemical synthesis , Benzene Derivatives/chemical synthesis , Intestinal Diseases, Parasitic/veterinary , Monieziasis/drug therapy , Nematode Infections/veterinary , Sheep Diseases/drug therapy , Animals , Anticestodal Agents/therapeutic use , Antinematodal Agents/therapeutic use , Benzene Derivatives/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Intestinal Diseases, Parasitic/drug therapy , Nematode Infections/drug therapy , Niclosamide/therapeutic use , SheepABSTRACT
The paper outlines a procedure for manufacturing the anthelminthic Azinox (biltricide) using the new interfacial transfer catalyst benzyl-di-propyl (beta-hydroxyethyl)ammonium chloride. Azinox has been shown to be identical to biltricide (praziquantel) in its properties. Azinox tests on models of Opisthorchis felineus in golden hamsters and of Hymenolepis nana in albino outbred mice have indicated that the agent is not inferior to biltricide in its antitrematodal and anticestodal activities. Azinox displayed a high activity at the preimaginal stages of O. felineus and H. nana and at the larval stage of H.nana.
Subject(s)
Anticestodal Agents/chemical synthesis , Antiplatyhelmintic Agents/chemical synthesis , Praziquantel/analogs & derivatives , Animals , Anticestodal Agents/therapeutic use , Anticestodal Agents/toxicity , Antiplatyhelmintic Agents/therapeutic use , Antiplatyhelmintic Agents/toxicity , Cricetinae , Drug Evaluation, Preclinical , Female , Hymenolepiasis/drug therapy , Hymenolepiasis/parasitology , Lethal Dose 50 , Male , Mesocricetus , Mice , Opisthorchiasis/drug therapy , Opisthorchiasis/parasitology , Praziquantel/chemical synthesis , Praziquantel/therapeutic use , Praziquantel/toxicityABSTRACT
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.
Subject(s)
Anticestodal Agents/chemical synthesis , Pyrimidines/chemical synthesis , Thiadiazoles/chemical synthesis , Animals , Anticestodal Agents/therapeutic use , Anticestodal Agents/toxicity , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Echinococcosis/drug therapy , Echinococcosis/parasitology , Echinococcus/drug effects , Female , Larva/drug effects , Male , Mice , Pyrimidines/therapeutic use , Pyrimidines/toxicity , Sigmodontinae , Thiadiazoles/therapeutic use , Thiadiazoles/toxicity , Time FactorsABSTRACT
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.
Subject(s)
Anticestodal Agents/chemical synthesis , Anticestodal Agents/therapeutic use , Animals , Anticestodal Agents/analysis , Anticestodal Agents/toxicity , Drug Evaluation, Preclinical/veterinary , Mice , Monieziasis/drug therapy , Niclosamide/therapeutic use , Sheep , Sheep Diseases/drug therapy , Spectrophotometry, Infrared , Technology, PharmaceuticalABSTRACT
A manufacturing procedure has been developed to prepare the anthelmintic bromoxane as a finely divided dosage form. The maximum toxic dose of the drug was 1 g per kg mice body weight. Its therapeutic dose in sheep fascioliasis was 20 mg/kg.
Subject(s)
Antiplatyhelmintic Agents/chemical synthesis , Benzamides/chemical synthesis , Fascioliasis/drug therapy , Sheep Diseases/drug therapy , Animals , Antiplatyhelmintic Agents/therapeutic use , Antiplatyhelmintic Agents/toxicity , Benzamides/therapeutic use , Benzamides/toxicity , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/veterinary , Fascioliasis/veterinary , Mice , Sheep , Technology, PharmaceuticalABSTRACT
Several derivatives of 2-methylthiobenzimidazoles were synthesized and assayed for anthelmintic activity. Following these studies, 2-methylthio-5-(1-chloronaphthyloxy-2)-6-chlorobenzimidazole (G-1557) has been selected as a tichinellacide for detailed investigations.
Subject(s)
Antinematodal Agents/chemical synthesis , Benzimidazoles/chemical synthesis , Animals , Antinematodal Agents/analysis , Antinematodal Agents/therapeutic use , Antinematodal Agents/toxicity , Benzimidazoles/analysis , Benzimidazoles/therapeutic use , Benzimidazoles/toxicity , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Male , Mebendazole/therapeutic use , Mice , Spectrophotometry, Infrared , Trichinella spiralis , Trichinellosis/drug therapySubject(s)
Anthelmintics/chemical synthesis , Benzamides/chemical synthesis , Sulfonamides/chemical synthesis , Thiadiazoles/chemical synthesis , Animals , Anthelmintics/analysis , Anthelmintics/therapeutic use , Anthelmintics/toxicity , Benzamides/analysis , Benzamides/therapeutic use , Benzamides/toxicity , Drug Evaluation, Preclinical , Electron Spin Resonance Spectroscopy , Mice , Particle Size , Spectrophotometry, Infrared , Structure-Activity Relationship , Sulfonamides/analysis , Sulfonamides/therapeutic use , Sulfonamides/toxicity , Thiadiazoles/analysis , Thiadiazoles/therapeutic use , Thiadiazoles/toxicity , Trichinellosis/drug therapySubject(s)
Anticestodal Agents/chemical synthesis , Benzazepines/chemical synthesis , Hymenolepiasis/drug therapy , Isoquinolines/chemical synthesis , Animals , Anticestodal Agents/therapeutic use , Anticestodal Agents/toxicity , Benzazepines/therapeutic use , Benzazepines/toxicity , Drug Evaluation, Preclinical , Isoquinolines/therapeutic use , Isoquinolines/toxicity , Mice , Structure-Activity RelationshipABSTRACT
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).
Subject(s)
Anticestodal Agents/chemical synthesis , Anticestodal Agents/therapeutic use , Echinococcosis/drug therapy , Hymenolepiasis/drug therapy , Quinolines/chemical synthesis , Quinolines/therapeutic use , Animals , Anticestodal Agents/toxicity , Drug Evaluation, Preclinical , Echinococcosis/parasitology , Female , Hymenolepiasis/parasitology , Male , Mebendazole/therapeutic use , Mice , Niclosamide/therapeutic use , Quinolines/toxicity , SigmodontinaeABSTRACT
Manufacturing process for anthelmintic embovin in a micronized form have been developed. Embovin in the micronized form exhibited the highest activity.
Subject(s)
Antinematodal Agents/chemical synthesis , Antinematodal Agents/therapeutic use , Pyrantel Pamoate/chemical synthesis , Pyrantel Pamoate/therapeutic use , Animals , Antinematodal Agents/chemistry , Antinematodal Agents/toxicity , Drug Evaluation, Preclinical , Mice , Nippostrongylus , Pyrantel Pamoate/chemistry , Pyrantel Pamoate/toxicity , Strongylida Infections/drug therapy , Technology, Pharmaceutical/methodsABSTRACT
Salicylanilides containing quinoline moiety were synthesized and examined for acute toxicity and antinematodal activity. All the compounds were shown to possess a low toxicity. In the trials on a nematodal model (Aspiculuris tetraptera, white mice), 2 compounds--G-1570 and G-1575--were shown to be highly effective.
Subject(s)
Antinematodal Agents/chemical synthesis , Quinolines/chemical synthesis , Salicylanilides/chemical synthesis , Animals , Antinematodal Agents/therapeutic use , Antinematodal Agents/toxicity , Drug Evaluation, Preclinical , Lethal Dose 50 , Mice , Oxyuriasis/drug therapy , Quinolines/therapeutic use , Quinolines/toxicity , Salicylanilides/therapeutic use , Salicylanilides/toxicity , Structure-Activity RelationshipSubject(s)
Antiplatyhelmintic Agents/chemical synthesis , Benzamides/chemical synthesis , Dicrocoeliasis/drug therapy , Fascioliasis/drug therapy , Animals , Antiplatyhelmintic Agents/analysis , Antiplatyhelmintic Agents/therapeutic use , Benzamides/analysis , Benzamides/therapeutic use , Chromatography, Thin Layer , Dicrocoeliasis/veterinary , Drug Evaluation/veterinary , Fascioliasis/veterinary , Sheep , Sheep Diseases/drug therapy , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
A synthesis is described and the results of toxicological trial of the potential anthelmintic agent G-1587 are presented. The agent is 2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-2H-[1, 2,5] thiadiazino [3,2-a] isoquinoline-4,4-dioxide. The agent was shown to have a low toxicity, the maximal sublethal dose for mice being 4.0 g/kg when given per os.
Subject(s)
Anticestodal Agents/toxicity , Isoquinolines/toxicity , Praziquantel/analogs & derivatives , Thiadiazines/toxicity , Animals , Anticestodal Agents/therapeutic use , Cricetinae , Drug Evaluation, Preclinical , Echinococcosis/drug therapy , Female , Hymenolepiasis/drug therapy , Isoquinolines/therapeutic use , Lethal Dose 50 , Male , Mesocricetus , Mice , Praziquantel/therapeutic use , Praziquantel/toxicity , Thiadiazines/therapeutic useABSTRACT
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.
Subject(s)
Antimalarials/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Quinolines/chemical synthesis , Animals , Antimalarials/therapeutic use , Antimalarials/toxicity , Chloroquine/analogs & derivatives , Chloroquine/therapeutic use , Drug Evaluation, Preclinical , Female , Heterocyclic Compounds/therapeutic use , Heterocyclic Compounds/toxicity , Malaria/drug therapy , Male , Mice , Plasmodium berghei , Quinolines/therapeutic use , Quinolines/toxicityABSTRACT
The toxicity and anthelminthic activity of the earlier synthetized tricyclic analogues of praziquantel and 4-acylpiperazinones-2 have been studied. Tricyclic compounds have shown the acute toxicity similar to that of praziquantel and neurotoxic effect typical of praziquantel. 4-acylpiperazinones-2 toxicity correlated with their anthelminthic effect. The determination of anthelminthic activity of the above compounds in opisthorchiasis and hymenolepiasis has shown that they are less effective than praziquantel or have no anthelminthic activity. A biological activity-structure relationship has been traced in the compounds under study.