CS271750B1 - N-maleoyl-2,6-diethylaniline - Google Patents

Abstract

Yet unknown N-maleoyl-2.6-diethylaniline was prepared. The synthesis of the above-mentioned compound is made in a reaction of 2.6-diethylaniline with the equivalent amount of maleic anhydride in benzene at the boil. The compound is antihelminthically effective against model helminth Nippostrongylus brasiliensis.<IMAGE>

Description

The present invention provides N-maleoyl-2,6-diethylaniline.

To date, several biologically active compounds based on 2,6-dialkylanilines have been known;

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

CH-COOH CH-CO-NH-

is anthelmintically effective against a relatively resistant model helminth of Nippostrongylus brasiliensis.

At the same time, a process for the preparation of said compound based on maleic anhydride and 2,6-diethylaniline has been found, which is characterized in that equivalently amounts of small anhydride and 2,6-diethylaniline are reacted together in benzene at reflux.

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

Example 1

Preparation of N-maleoyl-2,6-diethylaniline

Ualeinic anhydride (9.8 g, 0.1 mol) freshly crystallized from benzene was dissolved in benzene (50 cm 2). 2,6-Diethylaniline (14.9 g, 0.1 mol) was added to the solution and the reaction mixture was refluxed for 2 minutes. After cooling, petroleum ether (50 cm 3) was added to the mixture resulting in two layers in the reaction mixture. Cyclohexane was then added to the mixture until a homogeneous solution was formed from which a crystalline product began to precipitate. After standing overnight at 5 ° C, N-maleoyl-2,6-diethylaniline of m.p. 135 DEG-137 DEG C. in an amount of 23.0 g (93.0 56). The material was recrystallized from ethanol: water 1: 1 using activated carbon to give the product m.p. 136.5-138 ° C.

Mw : 247,30

For C ₁₄ H ₁₇ O ₃ calculated 56: C 68.00 H 6.93 N 5.66 found 56: 68.19 7.14 5.69

Example 2

Anthelmintic activity of a compound of the invention against a model helminth of Nippostrongylus brasiliensis

CS 271 750 Bl

The anthelmintic activity was determined in male rats 4-6 weeks of age and weighed 120-140 g. The experimental group consisted of 6 rats. The 2 groups were controlly invaded, untreated, one group treated with the standard levamisol preparator, and the saler 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 on day 3 after invasion (day 4 of the experiment), the second application was on day 6 after invasion. The dose size was 2 times and 150 mg kg ^{-1 of the} live mass. The application was performed without a hunger strike. The substances were suspended in Dorfman &apos; s and applied by weight in a volume of 0.65-12 cm &lt; 3 &gt;. Dorfman &apos; s alone were administered per os in the same untreated control groups. Dung examinations were performed on day 6 after invasion (day 7 of the experiment) before the second administration of the test substance or Dorfman reagent in the control groups. The trial was terminated by hunger strike on day 7 after invasion and killing of rats on day 8 after invasion (day 9 of the experiment). Efficacy was evaluated by performing a helmintological autopsy on the first two thirds of the small intestine. Treatment efficacy was expressed as a percentage of the Steward indirect activity method.

The compound of the invention showed an activity equivalent to 38.1% of that of the Standard (levamisole).

Significantly, the hitherto unknown compound of the new structure showed efficacy against the model helminth of Nippostrongylus brasiliensis, which represents 38.1% of the efficacy of the Standard Levamisole formulation (considered to be remarkable above 20% in this model helminth).

The compound of the invention may be used as an active ingredient of anthelmintic preparations, or as an intermediate for SalSie synthesis.

Claims (2)

N-Maleoyl-2,6-diethylaniline of the formula 2. A process for preparing a compound according to claim 1, which comprises reacting 2,6-diethylaniline with an equivalent amount of maleic anhydride in benzene at reflux for 1 to 15 minutes.