Judit Kosary

Synthesis, antihypertensive and α-adrenoceptor activity of novel 2-aminoalkyl-3(2H)-pyridazinones

Abstract A number of 2-phenoxyalkylaminoalkyl- and 2-[1,4]benzodioxanylmethylaminoalkyl-3(2H)-pyridazinones were synthesized and tested for hypotensive and antihypertensive activity as well as for α1- and α2-adrenoceptor binding affinities. Some derivatives, eg 5.5, 5.9, 5.12, 6.4 and 6.10, showed strong hypotensive/antihypertensive effect and high affinity for α2- and α1-adrenoceptors. Compound 5.5 was selected for clinical study. In its mode of action a potassium channel opening activity may also be involved.

Studies in the field of pyridazine compounds, 20. 6H-1,2,4-Triazino[4,3—b]1,2,4-triazolo[3,4—f]pyridazine, a novel angular ring system

The novel ring system, 6H-1,2,4-triazino[4,3—b]1,2,4-triazolo[3,4—f]-pyridazine was prepared either by ring closure of1-(1-ethoxycarbonylethylene)-2-(1,2,4-triazolo[4,3—b]pyridazinyl-6)-hydrazine derivatives (4, 5, 7) in polyphosphoric acid or of a hydrazine15 derived from pyridazino-1,2,4-triazine under the action of triethyl orthoformate. Compound8 showed a positive inotropic effect.ZusammenfassungDas neue Ringsystem 6H-1,2,4-Triazino[4,3—b]1,2,4-triazolo[3,4—f]-pyridazin wurde entweder durch Ringschluß der1-(1-Ethoxycarbonylethylen)-2-(1,2,4-triazolo[4,3—b]pyridazinyl-6)-hydrazin-Derivate(4, 5, 7) 4, 5, 7 in Polyphosphorsäure, oder aus einem von Pyridazino-1,2,4-triazin abgeleiteten Hydrazin15 durch Ringschluß mit Orthoameisensäuretriethylester hergestellt. Verbindung8 zeigte einen positiven inotropen Effekt.

Synthesis and hypotensive activity of novel 3-pyridazinyloxypropanolamines

We reported earlier the synthesis of some hypotensive pyridazinylhydrazones with direct peripheral vasodilatation [2]. Now to avoid tachycardia, the most frequent side-effect of peripherally acting hypotensive agents, we combined the pyridazine ring with an lalkylamino-2-hydroxypropyl group, which is a structural unit in many potent P-adrenoceptor antagonists and a new series of 3-pyridazinyloxypropanolamines (see [l]) was synthesized. The hypotensive effect, the change in heart rate and adrenoceptor antagonist activity (aand p-) of the compounds were tested.

Comparative Studies of Soluble and Immobilized Inulin-Hydrolysing Enzymes

ABSTRACT The possible use of inulin-hydrolysing enzymes in the qualitative and quantitative analysis and the preparative hydrolysis of fructans were studied. Whereas the cleavage of the terminal β -2,1-fructosylfructose bond could be easily achieved by different enzymes such as inulinase, invertase, and glucoamylase preparations, the special enzymic removal of the terminal glucose moiety was not accomplished. The inulin-hydrolysing enzymes were immobilized by covalent binding onto various supports and the kinetic properties of the preparations were characterized. The exo- and endo-inulinase components of the commercial Novo inulinase preparation were partially purified by ion exchange fractionation, using a modified procedure of the method described by Azhari et al. (1989). The formation of intermediate and end-products of the hydrolysis of inulin by the separated enzymes was analysed by spectrophotometric and thin-layer chromatographic methods. Beside mono- and oligosaccharides, two by-products of more apolar character were found in the reaction mixtures of both enzymes. Some of the immobilized inulinase preparations could be used effectively in bioreactors for the hydrolytic degradation of inulin.

Synthesis and positive inotropic activity of novel pyrimido-[5,4-b][1,4]oxazin-7(8H)-ones

Abstract Seventy-five compounds I were synthesized and tested for positive inotropic activity. Some derivatives ( 22, 24, 54 ) showed an activity comparable to that of amrinone. Compound 24 was selected for preclinical study. According to the biochemical and pharmacological data its activity may involve a novel mechanism(s).

Behaviour of Soluble Aminoacylase in Water-Organic Solvent Mixtures

Abstract The stability and the catalytic activity of the aminoacylase (E.C. 3.5.1.14.) were studied in various water-organic solvent mixtures at + 4°C. It was found that the concentration of the enzyme influences the kinetics, like in its aqueous solutions. The water concentration of the enzyme containing mixtures also influences the rate of inactivation of aminoacylase.