CS276322B6 - 2- / 2,6-Dimetylanilínokarhoxymetyltio / benzothiazol - Google Patents

Abstract

The previously unknown 2- [2,6-dimethylanilinoocarhoxymethylthio] benzothiazole was prepared. The synthesis of said compound is carried out by reacting the potassium salt of 2-mercaptobenzothiazole with N-chloroacetyl-2,6-dimethylaniline in a mixture of water, dimethyl sulfoxide and ethanol at reflux. The compound is antihelmintically active against the model helminth of Nippostron gylus brasiliensis.

Description

1

CS 276322 BS *>

The present invention provides 2- (2,6-dimethylanilinoocarboxymethylthio) benzothiazole.

So far, antihelmintic compounds based on 2,6-dialkylanilines have been known (Sidóová, E., Daněk, J. and Konečný, V., CS 271 750 and CS 271 297) and on the basis of benzotiazole (Sidóová, E. and Daněk , J., CS 271 547).

Now srae have found that a hitherto unknown compound of formula

it is antihelmintically active against a relatively effective against the relatively resistant Nippo strongylus brasiliensis helminth. At the same time, a method of preparing said compound was found by reacting 2-mercaptobenzothiazole (another name 2-benzothiazolintione) and N-chloroethyl ethyl-2,6-dimethylaniline, characterized in that the 2-mercaptobenzothiazole potassium salt is reacted with N-chloroacetyl -2,6-dimethylaniline in a mixture of water, dimethyl sulfoxide and ethanol at boiling.

The following examples illustrate, but do not limit, the preparation and properties of the compound of the invention. Example 1 Preparation of 2- [2,6-Dimethylanilinoocarboxymethylthio] benzothiazole 2-Mercaptobenzothiazole (5.0 g, 0.03 mol) was dissolved in a solution of potassium hydroxide (2.0 g, 0.03 mol) in a mixture of water ( 10 cm @ 3), dimethyl sulfoxide (25 .mu.m) and ethanol (250 cm @ 3). To the solution, N-chloroacetyl-2,6-dimethylaniline (5.9 g, 0.03mol) was added, the reaction mixture was heated to boiling and decolorized with charcoal. After cooling the filtrate to 5 ° C, 2- (2,6-dimethylanilinecarboxymethylthio) benzothiazole with mp 17B to 178.5 ° C was obtained in an amount of 8.2 g (83.3%) which did not require further purification. Mh = 328.46

% C: C 62.16 H 4.91 N 8.53 S 19.52 found%: 62.01 4.83 8y46 19.20 Example 2

Antihelmintic Activity of the Compound of the Invention on the Nip-postrongylus brasiliensis Model Helmet

Antihelmintic activity was determined in male rats 4 to 6 weeks old weighing 120 to 140 g. 2 groups were control, invaded, untreated, one group treated with the standard preparation of levamisole and the Sal group was the compound of the invention. The invasion was performed by freshwater Nippostrongylus brasiliensis III. invasive stage of 500 larvae per rat. The first application was made in the 3rd hole after the invasion (day 4), the second

Claims (2)

CS 276322 B6 2 days after invasion. The dose size was 2 times and 150 mg kg of body weight. Application was carried out without a previous hunger strike. The substances were suspended in a Dorfman reagent and applied at a weight of 0.65 to 12 cm. The rats in the control-treated groups were equally applied per os with Dorfman reagent alone. The faecal examination of the faeces was performed on day 6 after invasion (day 7 / trial) before the second administration of the test substance or Dorfman's reagent in the control groups. The experiment was terminated by hunger strike on day 7 after invasion and killing of rats on day 8 after challenge (day 9). Efficacy was assessed by performing helmintological autopsy at two-thirds of the small intestine. Efficacy was expressed as a percentage of indirect activity according to Steward. The compound of the present invention exhibited an efficacy equivalent to 54.4% efficacy of Standard (levamisole). Significant is the fact that the hitherto unknown compound of the new structure has shown efficacy over the model helminth of Nippostrongylus brasiliensis, which represents 54.4% of the efficacy of the standard preparation of levamisole (in this model helminth, a remarkable efficiency of 20% is considered). The compound of the present invention can be used as an active ingredient in an antihelmintic agent or as an intermediate for saline synthesis. Claims 1. 2- / 2,6-Dimethylanilino carboxymethylthio / benzothiazole of formula 2. A process for the preparation of a compound according to claim 1, wherein the potassium salt of 2-mercaptobenzothiazole is reacted with N-chloroacetyl-2,6-dimethylaniline in a mixture of water, dimethyl sulfoxide and ethanol at reflux.