3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates--new group of potential cardiotonic drugs.
3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates 6-11 were prepared by a Michael reaction of N-acetonylpyridinium chloride with 3-aryl-2-cyanothioacrylamides or by a one-pot three-carbon condensation of N-acetonylpyridinium chloride, aromatic aldehyde and 2-cyanothioacetamide, and their cardiotonic properties were studied. 3,4-trans-5-cyano-2-hydroxy-2-methyl-4-(3-nitrophenyl)-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolate 8 was considered as a lead compound in this series since it in vitro experiments (spontaneously beating rat atria) showed a cardiotonic activity similar to that of milrinone 2, however compound 8 induced activity at lover concentrations and without influence on chronotropic action of the heart. Unlike milrinone 2, thiolate 8 in vivo experiments (anaesthetized rats) did not influence blood pressure and heart rate. The acute toxicity of compound 8 was more than 10 times lower than that of milrinone 2.
Krauze
A
A
Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia. krauze@osi.lv
Vītoliņa
R
R
Garaliene
V
V
Sīle
L
L
Klusa
V
V
Duburs
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D020105:Milrinone / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011725:Pyridines; D013438:Sulfhydryl Compounds; D020105:Milrinone