CS264949B1 - N- (2-pyridyl) -2- (4-methyl-1-piperazinyl) acetamide and its dimaleinate - Google Patents

Abstract

The solution lies in the field of synthetic drugs. Its subject matter is N- (2-pyridyl) -2- (4-methyl-1-piperazinyl) acetamide and its dimaleinate, which show significant antiulcer activity in the rat indomethacin ulcer inhibition test. The compound can be prepared by substituting N- (2-pyridyl) -2-chloroacetamide with 1-methylpiperazine.

Description

The present invention relates to N- (2-pyridyl) -2- (4-methyl-1-piperazinyl) acetamide of the formula I

nchcoch ₂ n nch ₃ and its dimaleinate.

The compound of the invention of formula I and its maleic acid salt are characterized by intense anti-ulcer activity and are suitable for the treatment of ulcer disease. In the pharmacological and biochemical-pharmacological tests, the compound of formula I was used in the form of dimaleinate, but the reported doses are recalculated on the basis of I. The substance is characterized by relatively low acute toxicity in mice; LD ≥ 706 mg / kg when administered orally. Other data also relate to oral administration. Anti-ulcer efficacy was evaluated in an indomethacin ulcer inhibition test in rats.

In this test, the median effective dose of the compound of formula (I) is λ d = 28.4 mg / kg. Thus, the substance is even more effective than the proven anti-ulcer preparation pyrenzepine (Kitagawa H. et al .: Arzneim-Forsch, 28, 2 122, 1978), whose Ε, -θ in the same test is 32.7 mg / kg. As a criterion for the anticholinergic effect of the compound of formula I, its mydriatic action in mice was evaluated.

At an oral dose of 100 mg / kg, the substance acts mydriatically in all animals in the test group. The compound of Formula I exhibits affinity for muscarinic receptors in rat brain using 0.5 nM / H / quinuclidylbenzilate as ligand; the mean inhibitory concentration of the compound of formula I, i.e. IC 50, is 3,759 nM. At an oral dose of 50 mg / kg, the compound of formula I also has indications of antisecretory action (in rats with pyloric ligature), both in terms of both free acid output and total acidity.

The compound of formula I according to the invention can be prepared by substitution reaction of the known N- (2-pyridyl) -2-chloroacetamide (Hach V., Protiva M., Chem. Listy 47, 729, 1953; Collect. Czech. Chem. Commun. 18, 684). , 1953) with 1-methylpiperazine. It is preferred to use at least 100% excess of this amine, which then serves not only as a reaction component but also as a reaction medium and as a condensing agent. Preferably, the reaction can be carried out in chloroform at a slightly elevated temperature, i.e. 30 to 60 ° C. The reaction proceeds even faster in boiling chloroform. The compound of formula I in the form of a base is oily; its identity was ensured by spectral methods; neutralization with maleic acid in ethanol gives a crystalline dimaleinate which melts at 150-153.5 ° C. The following exemplary embodiment is illustrative of the preparation possibilities of the compound of formula I and its dimaleinate.

Example

A mixture of 8.5 g of N- (2-pyridyl) -2-chloroacetamide (literature cited), 10 g of 1-methylpiperazine and 50 ml of chloroform is stirred for 4 h at 50 ° C. After cooling, the mixture is quenched by the addition of 100 ml of water, shaken, the organic layer is separated, dried and evaporated. 6.7 g of oily base N- (2-pyridyl) -2- (4-methyl-1-piperazinyl) acetamide are obtained. Neutralization with maleic acid in ethanol gives a crystalline dimaleinate which crystallizes from ethanol and melts in the pure state at 150-153.5 ° C.

Claims (1)

SUBJECT OF THE INVENTION N- (2-pyridyl) -2- (4-methyl-1-piperazinyl) acetamide of formula I NHCOCHoN NCHq ^{of ú} (I) and its dimaleinate.