[Potential cardiotonic agents. 10. Synthesis and positive inotropic action of 5-(4-pyridinyl)- and 5-phenyl-substituted 2-alkylthio-3-cyan-pyridines and their S-oxidation products]. / Potentielle Kardiotonika. 10. Mitteilung3: Darstellung und positiv inotrope Wirkung von 5-(pyrid-4-yl)-und 5-phenyl-substituierten 2-Alkylthio-3-cyanpyridinen und ihren S-Oxidationsprodukten.

The alkylation of the 5-(4-pyridinyl)- and 5-phenyl-substituted 3-cyan-2(1H)-pyridinethiones 1 with alkyl iodides and halomethylcarbonyl compounds led to the 2-alkylthio-pyridines 3a-c, 3e, 3f and the thieno[2,3-b]pyridines 4, respectively. In an other way the 2-ethylthio-5-(4-pyridinyl)pyridines 3b and 3d were formed from the corresponding 2-chloroderivatives and ethylmercaptan. By means of oxidation of the 2-alkylthio-pyridines 3 with 3-chloroperbenzoic acid and potassium permanganate, respectively, the 2-sulfinyl- and 2-sulfonyl-pyridines 5 and 6 were obtained. The 3-cyano-5-(4-pyridinyl)pyridine-2-sulfonic acid 7 was prepared by oxidation of the 2(1H)-pyridinethione 1a with potassium permanganate. Some derivatives possess positive inotropic properties.

[Potential cardiotonic agents. 8. 2-acyloxyalkylamino-, 2-acyloxyalkoxy-, and 2-acylaminoalkylamino-3-cyan-5-(pyrid-4-yl) pyridine]. / Potentielle Kardiotonika. 8. Mitteilung: 2-Acyloxyalkylamino-, 2-Acyloxyalkoxy- und 2-Acylaminoalkylamino-3-cyan-5-(pyrid-4-yl) pyridine.

By acylation of our previously described cardiotonic active 2-hydroxyalkylamino, 2-hydroxyalkoxy, 2-aminoalkyl-amino and 2-piperazino substituted 3-cyano-5-(4-pyridinyl) pyridines with acetic anhydride, propionic anhydride or aroyl and heteroaroyl chlorides, respectively, the corresponding in position 2 O- or N-acylated 3-cyano-5-(4-pyridinyl)pyridines were prepared. Cardiovascular activity of the obtained derivatives is discussed in comparison with that of the parent compounds.

[Potential cardiotonics. 7. Synthesis and cardiovascular effects of 5-(4-pyridinyl)-, 6-methyl-4-(4-pyridinyl) and 6-methyl-5-phenyl-substituted 3-cyano-2-aminoalkylamino-pyridines]. / Potentielle Kardiotonika. 7. Mitteilung5: Darstellung und kardiovaskuläre Eigenschaften von 5-(pyrid-4-yl)-, 6-methyl-5-(pyrid-4-yl)- und 6-methyl-5-phenyl-substituierten 2-Aminoalkylamino-3-cyan-pyridinen.

The title compounds were synthesized by treating of 2-chloro-pyridines 1-3 with the appropriate aminoalkylamines or piperazines. In isolated guinea pig atria some compounds showed greater positive inotropic activity than amrinone. Heart rate was decreased or remained unchanged. In anesthetized dogs some derivatives exerted a dose-dependent increase in myocardial contractility and, additionally, a decrease in blood pressure.

[Potential cardiotonic agents. 6. Synthesis and cardiovascular properties of 5-(4-pyridinyl)-, 6-methyl-5-(4-pyridinyl)- and 6-methyl-5-phenyl-substituted 3-cyano-2-oxaalkyoxy-pyridines]. / Potentielle Kardiotonika. 6. Mitteilung: Darstellung und kardiovaskuläre Eigenschaften von 5-(pyrid-4-yl)-, 6-methyl-5-(pyrid-4-yl)- und 6-methyl-5-phenylsubstituierten 3-Cyan-2-oxaalkoxy-pyridinen.

The headline compounds were prepared by the reaction of 2-chloropyridines 1-3 with the appropriate alcohols in presence of potassium hydroxide and the sodium alkoxides, respectively. Especially some of the 3-cyano-2-hydroxyalkoxy-5-(4-pyridinyl)pyridines showed remarkable positive inotropic potency and, additionally, a vasodilator activity. In spontaneously beating isolated guinea pig atria they had a greater activity than amrinone.

[Potential cardiotonic agents. 4. Synthesis, cardiovascular activity, molecular and crystal structure of 5-phenyl- and 4-(4-pyridinyl)-substituted 2(1H)-pyridinethiones]. / Potentielle Kardiotonika. 4. Mitteilung5: Darstellung, kardiovaskuläre Wirksamkeit, Molekül- und Kristallstruktur von 5-phenyl- und 5-(pyrid-4-yl)-substituierten 1,2-Dihydro-pyrid-2-thionen.

Cyclisation of the vinylogous amidinium salt 1 or the 4-ethoxy- and 4-morpholino-3-butene-2-ones, respectively, 4 and 6 with cyano-thioacetamide yielded the 5-(4-pyridinyl)-, 6-methyl-5-(4-pyridinyl)- and 6-methyl-5-phenyl-, respectively, substituted 3-cyano-2(1H)-pyridinethiones 3, 5 and 7. The 2(1H)-pyridinethiones 3, 5 and 7a as well as the in 3-position unsubstituted or carbamoyl substituted derivatives 8 and 9 were obtained from the corresponding 2-chloro-pyridines and potassium sulfide, too. Especially compound 5 showed remarkable positive inotropic potency and, additionally, vasodilator activity. The molecular and crystal structure of 5 have been determines by X-ray structure analysis. Based on the molecular structure charge distribution and electrostatic potential were evaluated. The results are discussed in comparison with those of milrinone.

[Potential cardiotonic agents. 2. Synthesis and pharmacologic properties of 5-(pyri-4-yl)- and 5-phenyl substituted 3-cyano-6-methyl-2-oxaalkylaminopyridines]. / Potentielle Kardiotonika. 2. Mitteilung: Synthese und pharmakologische Eigenschaften von 5-(pyrid-4-yl)- und 5-phenylsubstituierten 3-Cyan-6-methyl-2-oxaalkylamino-pyridinen.

The authors describe the preparation, the physicochemical properties and the results of evaluation of positive inotropic and vasodilator activities in a series of 5-(4-pyridinyl)- and 5-phenyl-substituted 3-cyano-6-methyl-2-oxaalkylamino-pyridines. Some of the compounds are comparable in their positive inotropic potency to that of amrinone and cause, additionally, a decrease in blood pressure.