[Potential cardiotonic agents. 4. Synthesis, cardiovascular activity, molecular and crystal structure of 5-phenyl- and 4-(4-pyridinyl)-substituted 2(1H)-pyridinethiones].
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.
Hagen
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Akademie der Wissenschaften der DDR, Institut für Wirkstofforschung.
Rumler
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A
Reck
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Hagen
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A
Labes
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Heer
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D003460:Crystallization; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D020105:Milrinone; D008968:Molecular Conformation; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013871:Thiones / Q000138:chemical synthesis / Q000494:pharmacology; D014961:X-Ray Diffraction
D002316:Cardiotonic Agents; D004095:Dihydropyridines; D011725:Pyridines; D011728:Pyridones; D013871:Thiones; D020105:Milrinone
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.