Studies on quinoxaline derivatives. Synthesis of quinoxalylamino-1,3-diazacycloalkanes with potential hypotensive activity.

A series of quinoxalylamino-1,3-diazacycloalkanes was obtained by the reaction of the corresponding substituted aminoquinoxalines with alcohols and amines. The effect of selected compounds on the blood pressure of anaesthesized normotensive rats was studied.

Studies on pyrazine derivatives. XXX. Synthesis of pyrazinylamino-1,3-diazacycloalkanes of potential circulatory activity.

A series of pyrazinylamino-1,3-diazacycloalkanes was obtained by reaction of the corresponding substituted aminopyrazines with aliphatic amines. Selected compounds were studied with respect to their potential circulatory activity. The effect on the blood pressure, isolated rat tail artery and heart atria, and an influence on the human blood platelet aggregation were investigated.

Quantitative relationships between hydrophobicity and hypotensive activity of diazacycloalkane derivatives.

The effect of a series of ten newly synthesized diazacycloalkanes as well as four standard imidazoline drugs on blood pressure of anesthetized normotensive rats was measured. The hypotensive activity of the agents studied, expressed as logit of the maximum effect, logit E(%), was quantitatively related to the changes in their chemical structure. Highly significant relationship between the hydrophobicity parameter, sigma f, and logit E(%) value has been found.

[Studies on pyrazine derivatives. XXVI. Synthesis and tuberculostatic activity of N-pyrazinylthiourea]. / Badania nad pochodnymi pirazyny. XXVI. Synteza i aktywnosc tuberkulostatyczna N-pirazynylotiomoczników.

2-Amino-3-chloropyrazine and 2-amino-6-chloropyrazine were reacted with appropriate sodium alkoxides to give 2-aminopyrazine derivatives with the methoxy, benzyloxy, chlorobenzyloxy, dichlorobenzyloxy, bromobenzyloxy or dibromobenzyloxy group at positions 3 and 6 (I-XIV). The obtained compounds were converted into N-pyrazinyl-N'-benzoylthioureas (XV-XXXI) by reacting with benzoyl isothiocyanate. Their hydrolysis yielded N-pyrazinylthioureas XXXII-XLVII. Analogical reactions of alkoxyaminopyrazines with p-chlorophenyl isothiocyanate or 2,6-dichlorophenyl isothiocyanate afforded corresponding N-pyrazinyl-N'-(p-chlorophenyl)thioureas and N-pyrazinyl-N'- (2,6-dichlorophenyl)thioureas (XLVIII-LVIII). The obtained compounds were found to display tuberculostatic in vitro activity with MIC values from 8 meg/cm3 to 1000 mu meg/cm3.

Structure and alpha-adrenergic activity of pyrazinimidazolines.

The effects of newly synthetized pyrazinimidazolines on the contraction of isolated rat tail artery and on the chronotropic action of rat atria as well as the effects on blood pressure in anaesthetized rats were determined. The structure-activity relationships were studied, including standard imidazoline drugs. Starting from practically inactive derivatives the step-by-step structural modifications have been made resulting in markedly active chemical congeners, which were designed, synthetized and tested pharmacologically.

A search for new antihypertensive agents. I. Alpha-adrenergic activity and selection of structures among pyrazine substituted imidazolines.

A group of new pyrazinylimidazolines was prepared and their effect on the contraction of isolated rat tail artery as well as their effect on blood pressure in urethane anesthetized normotensive rats were tested. The biological responses were compared to those elicited by standard imidazoline drugs and structure-activity relationships were analysed. The new chemical derivatives were subsequently synthetized and tested pharmacologically. Basing on the experimental results obtained and comparing these to the reported data on arylimidazolines the following suggestions have been put forward concerning the further modifications of alpha-adrenergically active pyrazinylimidazolines: 1) a distance of about 5 A should separate imidazoline nitrogen and pyrazine nucleus, 2) bond refractivity of the separating bridge should be above 5.33, 3) hydrophobicity of substituents in pyrazine ring must be possibly high.