Synthesis and positive inotropic evaluation of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted piperazine moieties
| Autor: | Li-ping Liu, Xun Cui, Jia-Chun Liu, Long-Xu Ma, Yan Wu, Hu-Ri Piao, Bai-ri Cui |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Chronotropic
Inotrope Stereochemistry Clinical Biochemistry Left atrium Pharmaceutical Science Increased stroke volume Biochemistry Piperazines Ventricular Function Left chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Animals Molecular Biology Piperazine Dose-Response Relationship Drug Organic Chemistry Stroke Volume Triazoles medicine.anatomical_structure chemistry Mechanism of action Molecular Medicine Milrinone Phthalazines Rabbits medicine.symptom Phthalazine medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 24(7) |
| ISSN: | 1464-3405 |
| Popis: | Four series of [1,2,4]triazolo[3,4- a ]phthalazine and tetrazolo[5,1- a ]phthalazine derivatives bearing substituted piperazine moieties were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume in isolated rabbit-heart preparations. Several compounds were developed and showed favorable activities compared to the standard drug milrinone, with (4-([1,2,4]triazolo[3,4- a ]phthalazin-6-yl)piperazin-1-yl)( p -tolyl)methanone ( 5g ) being identified as the most potent with an increased stroke volume of 19.15 ± 0.22% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10 –5 M. A preliminary study of mechanism of action revealed that 5g displayed its positive inotropic effect may be related to the PDE-cAMP-PKA signaling pathway. Compounds exhibiting inotropic effects were also evaluated in terms of the chronotropic effects. |
| Databáze: | OpenAIRE |
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