Studies on kinetic parameters and stability of aminoacylase in non-conventional media.

Catalytic properties and conformational stability of aminoacylase (N-acylamino acid amidohydrolase, EC 3.5.1.14) were studied in water-N,N-dimethylformamide (DMF) and water-dioxane solvent mixtures. Beside the prompt inhibition the solvents caused further inactivation during incubations. In the presence of 5% DMF content the inactivation proceeds with a well-measurable rate (t1/2 39 min), while in the case of 20% DMF the enzyme practically lost its starting activity during 50 min incubation (t1/2 13 min). The K(m) value of the enzyme increased about three times with increasing DMF concentrations up to about 2.6 M DMF, while the Vmax value decreased practically to zero in the same concentration range.

The effect of environmental pollution on the function of enzymes of active skeleton muscle. Part 1: An adequate method to study the effect of metal ions on the activity of phosphofructokinase.

The possibilities of exact measuring the effect of metal ions on the activity of phosphofructokinase (PFK) by means of both a heat inactivation and an auxiliary enzyme system were studied. It was found that both methods are suitable for measuring the inhibition of phosphofructokinase by metal ions. It was further found that metal ion concentrations causing 50% deactivation of PFK could not considerably influence the measuring capacity of the auxiliary enzyme system.

Synthesis and hypotensive activity of some heterocyclic analogues of GYKI-12 743.

[1,4]Benzodioxanylmethyl-, [1,4]benzodioxanylmethylaminopropyl- and phenoxyethylaminoethyl-substituted lactams were synthesised and their hypotensive activity was investigated. Some of these compounds show moderate to high hypotensive effect, but they had more toxic and/or side effects than GYKI-12 743.

Synthesis of pyridylthiazoles as antisecretory agents.

4-(3-Pyridyl)thiazole and 2-methylimidazo[1,2-a]pyridine derivatives with anticholinergic antisecretory activity were synthesized. Most of the compounds (3-16) were formed from carbohydrazide 2 and carbonitrile 9. Some thiazole derivatives, most of them containing nitrogen attached to the thiazole C-2 (19-20), were prepared from 17 and 18 by known method. Compounds 12 and 19b exerted a significant antisecretory whereas 5b, 12 and 19b an antiulcer activity.

The CNS effects of 5-aminobenzoic acids inhibiting the biosynthesis of prostaglandins.

It was found that the 2,5-diaminobenzoic acid derivatives 1 activating the biosynthesis of prostaglandins have CNS side effects. The replacement of the 2-NH group in 1 by O or S resulted an inhibition of prostaglandin biosynthesis and increased CNS activity.

Synthesis of thiazole derivatives with positive inotropic effect.

Thiazole derivatives with potential positive inotropic effect were synthesized. The highest activity (medium positive inotropic effect) was exhibited by ethyl 2-(2-hydroxyethylamino)-4-phenylthiazole-5-carboxylate (3b) of which several derivatives have been prepared. Among these derivatives only those which could presumably easily removed in the living organism to give 3b exhibited a medium positive inotropic effect (6, 8b). It was assumed that the effect of 3b had a beta-agonist character.

Studies in the field of pyridazine compounds. Part 21. Structural studies on 6-H-pyrimido[1,2-b]-1,2,4-triazolopyridazines.

The structure of 7,8-dihydro-6H-pyrimido [1,2-b]-1,2,4-triazolo [3,4-f] pyridazine (2a) was confirmed by 1H and 13C NMR spectroscopy and by preparation of the isomeric [5,1-f] pyridazine 3. Some derivatives of 6H-pyrimido [1,2-b]-1,2,4,-triazolo [3,4-f]pyridazine were prepared. Compounds 2a, 2b and 9a showed a positive inotropic effect.

Preparation of new [1,2,4]triazolo[4,3-b]pyridazines. Part 12: Studies in the field of pyridazine compounds.

6-Substituted-[1,2,4]triazolo[4,3-b]pyridazine-3-methanol, -aldehyde, -nitrile, -chloromethyl and -aminomethyl derivatives of potential antihypertensive activity were synthesized. The reduction of methyl[1,2,4]triazolo[4,3-b] pyridazine-3-carboxylate by lithium aluminium hydride and potassium borohydride was examined. The new compounds failed to exhibit hypotensive or antihypertensive effect. Compound 2a was a minor metabolite of GYKI-11679 [7].