CS276388B6 - 2- (2-Ethyl) methylphenylcarbanioylmethylthio / benzothiazole - Google Patents

Abstract

A previously unknown 2-[2-ethyl-6-methylphenylcarbamoylmethylthio] benzothiazole has been prepared. The synthesis of the compound is carried out by the reaction of 2-hydroxybenzothiazole with H-chloroacetyl-2-ethyl-o-methylaniline in the presence of potassium hydroxide in a mixture of water, dimethyl sulfoxide and ethanol by heating to boiling. The compound is anthelmintic effective against the model helminth Nippostrongylus brasiliensis.

Description

The present invention provides 2- (2-ethyl-6-methylphenylcarbamoylmethylthio) benzothiazole.

Hitherto known 2- / 2,6-dimethylanilinocarboxyethylbethylthio / benzothiazole, by another name

2- (2,6-dimethylphenylcarbonylmethylthio) benzothiazole, which has shown antihelminthic activity against Nippostrongylus brasiliensia [Sidóová, E., Daněk, J. and Konečný, V ,, čs. patent 276 322 /.

We have now found that a hitherto unknown compound of the formula

ch ₃ is anthelmintically effective against the model belmite Nippostrongylua brasiliensia.

At the same time, a method for preparing the title compound by reacting 2-mercaptobenzothiazole with N-chloroacetyl-2-ethyl-6-methylaniline in the presence of potassium hydroxide, in a mixture of dimethyl sulfoxide, ethanol and water, was discovered.

The following examples illustrate, but do not limit, the preparation and properties of the compound of the invention.

Example 1

Preparation of 2- (2-ethyl-6-methylphenylcarbamoylmethylthio) benzothiazole

To a solution of potassium hydroxide (2.0 g, 0.03 mol) in water (10 cm 3) was added 2-mercaptobenzothiazole (5.0 g, 0.03 mol), followed by dimethyl sulfoxide (25 cm 3) and ethanol (250 The reaction mixture was heated to clear, N-chloroacetyl-2-ethyl-6-methylaniline was added, then boiled and decolorized with activated charcoal. To the filtrate was added 60 ° C warm water (100 cm 3) and, after cooling to 5 ° C, a crystalline product was isolated therefrom, which was washed by batches (100 cm 3) of ethanol-water 1: 1. pure 2- (2-ethyl-6-methylphenylcarbamoylmethylthio) benzothiazole with m.p. 157.5-158.0 ° C in an amount of 9.4 g (91.5%), which did not require further purification.

M.h. = 342.48 For calculated%: 0 63.13 H 5.30 N 8.18 S 18.72 % detected: 63.25 5.25 8.07 18.45

CS 276388 B6 2

Example 2

The anthelmintic activity of the compound of the invention against the model helmint Nippostrongylus brasiliensis

Anthelmintic activity was determined in male rats aged 4 to 6 weeks and weighing 120 to 140 g. The experimental group always consisted of 6 rats. 2 groups were control-invaded, untreated, one group treated with the standard levamisole preparation and the other group received the compound of the invention. The invasion was performed with fresh larvae of Nippostrongylus brasiliensis III. invasive stage of 500 larvae per rat. The first application was performed 3 days after the invasion / 4. day of experiment /, second application on day 6 after invasion. The dose size was 2 times and 150 mg.kg ^- ^ · of living matter. The application was performed without a previous fast. The substances were suspended in Dorfman's reagent and applied by weight in a volume of 0.65 to 12 ctn-1. Dorfman's reagent alone was orally administered to rats in the untreated control groups. Corpological examination of faeces was performed on day 6 after inasia / 7. day of experiment / before the second application of test substance or Dorfman's reagent in control groups. The experiment was terminated by fasting on the 7th day after the invasion and by killing the rats on the 8th day after the invasion / 9. day of experiment. Efficacy was evaluated by performing a helminth autopsy on the first two-thirds of the small intestine. Efficacy was expressed as a percentage by Stewards' indirect activity method.

The compound of the invention showed an activity corresponding to 48.4% of the activity of the standard (levamisole).

Significantly, the hitherto unknown compound of the new structure showed activity against the relatively resistant model helmint Nippostrongylus brasiliensis, which represents 48.4% of the activity of the standard levamisole preperate. / for said model helmint it is considered to be a remarkable efficiency ’above 20% /. It is also significant that the compound according to the invention contains a 2-ethyl-6-methylanilino group instead of the 2,6-dimethylanilino group of the hitherto known preparation, i.e. it contains a less toxic group.

The compound of the invention can be used as an active ingredient of anthelmintic preparations alone or in admixture with other substances, or as an intermediate in the synthesis process.

Claims (2)

Example 2 Antihelmintic activity of a compound of the invention against a model helminth Nippostrongylus brasiliensis Antihelmintic activity was determined on male rats 4 to 6 weeks of age weighing 120 to 140 g. , one group treated with a standard preparation of levamisole and a larger group was administered the compound according to the invention. Invasion was performed with fresh larvae of Nippostrongylus brasiliensis III. invasive stage of 500 rat larvae. The first application was performed at 3- day after invasion / 4. day of experiment /, second application on day 6 after invasion. The dose size was 2 times and 150 mg / kg bodyweight, The application was carried out without a hunger strike. The substances were suspended in the Dorf-mann reagent and applied according to the weight in the volume of 0.65 to 12 cm- The rats in the control untreated groups were equally applied per os on the Dorftan reagent alone. The faecal examination of the faeces was performed at 6, day after inactivity / 7. the test / before the second application of the test substance, or the Dorfman reagent in the control groups. The experiment was terminated by hunger strike at 7 days after invasion and killing of rats at 8, day after invasion / 9. day of experiment /. Efficacy was assessed by performing helmintological dissection of the first two thirds of the small intestine. Efficiency was expressed as a percentage of the method of indirect activity according to Steward. The compound of the invention exhibited an efficacy equivalent to 48.4% of the efficacy standard (levamisole). Significant is the fact that the hitherto unknown compound of the new structure has shown efficacy against the relatively resistant Nippostrongylus brasiliensis model helminth, which represents 48.4% of the efficacy of the standard levamisole preperate. / for the model model, it is considered to be a remarkable efficiency above 20% /. Furthermore, it is important that the compound of the invention contains 2-ethyl-6-methylanilino-group instead of 2,6-dimethyl-anilino-group, hitherto known to contain a less toxic group. The compound of the present invention can be used as an active ingredient of antihelmintic preparations alone or in admixture with an inert agent, or as an intermediate for past synthesis. Claims 1. 2- / 2-Ethyl-6-methylphenylcarbamoylraethylthio / benzothiazole Formula X-C-S-CHg-CO-NH · 2. A process for the preparation of a compound according to claim 1, characterized in that 2-mercaptobenzothiazole is reacted with N-chloroacetyl-2-ethyl-6-methylaniline in the presence of potassium hydroxide in a mixture of water, dimethyl sulfoxide and aniline by heating to boiling.