CS268645B1 - Derivatives of thioallophanic acid - Google Patents

Abstract

- (Dwg.No.0/0)(0/0)

Description

The present invention relates to methyl esters at the 4-position of disubstituted thioalofanoic acids of the general formula

X N-CS-NHCOCH ₃ (I) wherein X is a sulfur atom or an imine group / substituted with methyl.

These novel substances, which have not yet been described, exhibit useful anthelmintic activity, in particular against the model helminth of Hymenolepis nana.

The compounds of the formula I according to the invention can be prepared by reacting thiomorpholine or N-methylpiperazine with methoxycarbonyl isothicyanate in acetone at 20 to 40 ° C.

Methoxycarbonyl isothiocyanate was obtained by reacting potassium thiocyanate with chloroformic acid methyl ester in boiling acetone.

Evaluation of anthelmintic activity against model helminth Hymenolepis nana:

The tests were performed on male H strain mice weighing 10-13 g in groups of 6 each. Of the three control groups, the controls were invaded, untreated, the third invaded, treated with a standard formulation - niclosamide piperazine salt - against which the efficacy of the compounds was compared. Invasion was performed by probing orally with 500 mature Hymenolepis nana tapeworm eggs in a volume of 0.25 ml / mouse. Compounds of formula I were administered on the 13th and 14th day after the invasion by oral gavage at a dose of 150 mg.kg ¹ liveweight as homogenates Dorfmannově agent. Mice were sacrificed on day 3 after administration and, after total colonic tapeworm counts at complete, helminthological dissection of the small intestine of mice, anthelmintic efficacy was determined by Steward's indirect activity calculation. The standard was also applied to the 13th and 14th day after the invasion in a dose of 150 mg.kg ¹ bodyweight.

The anthelmintic activity of the compounds of formula nana, expressed as a percentage by the indirect method

Hymenolepis: no

Even against the model helminth activity according to steward is the follower according to the substance according to example example 1

75.2%

71.2% in it

Method of satisfactory yields. DETAILED DESCRIPTION OF THE INVENTION The following examples are merely illustrative of the preparation of the compounds of the present invention and provide the desired products of the invention.

Example i

4- (Methoxycarbonylamino thiocarbonyl) thiomorpholine

To a solution of potassium thiocyanate (5.83 g, 0.06 mol) in acetone (125 ml), 5.67 g (4/62 1 0.06 mol) of methyl chloroformate were added and the mixture was refluxed for 30 min. · After cooling. The precipitated potassium chloride was aspirated to 20 ° C and 5/16 g (5.02 mL * 0.05 mol) of thiomorpholine was added dropwise to the filtrate with stirring. The liquid reaction mixture was stirred for 5 h, then distilled under vacuum in acetone, the liquid residue diluted with 60 mL of methanol and left in a refrigerator at 5 ° C for 24 h. The precipitate was filtered off with suction and recrystallised from methanol · Get 6.05 g (55.0%) of material melting at 124-125 ° C of the composition ^C 7 ^H ₁₂ ^N 2 ^S 2 ° 2 *

Example 2

4- (Methoxycarbonylaminothiocarbonyl) -1-methylpiperazine

The method described in Example 1 was potassium thiocyanate (5.83 g, 0.06 mol)

5/67 g (0/006 mol) of methyl chloroformate and 5/01 g (0.05 wol) of 1-methylpiperazine prepared as a crude material, which was recrystallized from methanol · Obtained

5.27 g (48.6%) of a substance melting at 158-159 ° C, depositing C ₈ H ₁₅ N ₃ 0 ₂ S.

Claims (1)

SUBJECT OF THE INVENTION Thioalofanoic acid derivatives of the general formula I X is N-CS-NHCOOCH ₃ wherein X is a sulfur atom or an imine group substituted with methyl.