Design, synthesis and vasorelaxant activity of R, S-1-(substituted phenyl)-4-3-(naphtha-1-yl-oxy)-2-hydroxypropyl-piperazine derivatives / 药学学报
Acta Pharmaceutica Sinica
;
(12): 735-740, 2007.
Article
in Chinese
| WPRIM
| ID: wpr-268587
ABSTRACT
According to the results of activity-structure relationship (SAR) studies of alpha1-adrenoceptor antagonists hydantoin-phenylpiperazine and benzimidazo-arypiperazine derivatves, to design and synthesize a series of novel phenylpiperazine alpha1-adrenoceptor antagonists with more potent vasorelaxant activity, active metabolites of naftopidil were used as lead compounds. Ten novel R,S-1-substituted phenyl-4-[3-(naphthal-yl-oxy)-2-hydroxy propyl]-piperazine were designed and synthesized, their vasorelaxant activity was evaluated by calculating inhibition rate of phenylephrine-induced vasocontration of rabbit artery trips. Five compounds exhibited vasorelaxant activity, and compound 16 showed significant vasorelaxant activity in vitro. At 0.01 and 1 micromol x L(-1), its inhibition rates were 7.03% and 22.72%, respectively. This compound possessed ideal vasorelaxant activity in vitro, and would be selected for further anti-hypertension evaluation in vivo. Moreover, by analyzing the primary activity and structure relationship of these compounds, it could be concluded that the SAR results of the reported phenylpiperazine alpha1-adrenoceptor antagonists could be used for reference in designing novel derivatives of naftopidil with optimal pharmacological properties.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Piperazines
/
Structure-Activity Relationship
/
Vasoconstriction
/
In Vitro Techniques
/
Molecular Structure
/
Chemistry
/
Adrenergic alpha-1 Receptor Antagonists
/
Antihypertensive Agents
Limits:
Animals
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2007
Type:
Article
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