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Title: A search for selective [alfa]1-adrenoceptor antagonists among arylpiperazine derivatives of phenytoin
Abstract:
The work describes a search for new α1- adrenoceptor antagonists as chemical modifications of lead structure AZ-99 (1-[2- Hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]- 3-methyl-5,5-diphenyl-imidazolidine-2,4- dione). In the introduction, the newest a1- adrenoceptors classification was shown as well as structures of phenylpiperazine α1- adrenoceptor antagonists. The investigations include: synthesis of new compounds, crystal structure analysis, molecular modeling, an evaluation of physicochemical parameters of the obtained compounds (solubility, octanolwater partition coefficient), pharmacological screenmg and QSAR analysis. The new compounds were obtained in three- or foursteps synthesis. Solubilities of the obtained compounds were investigated theoretically and experimentally. The obtained compounds were tested on their affinity for α1- and α2- ARs in radioligand binding assays. Selected compounds were evaluated on their activity for α1-adrenoceptor subtypes in functional bioassays. For the obtained compounds, tests in vivo were performed to evaluate their antiarrhythmic activity and their influence on blood circular system. Most of the obtained compounds showed higher water solubility and better pharmacological properties than that of the lead. Most active compounds contain 2-alkoxyphenylpiperazine moiety. Among them the best one was compound 58a ; , containing butyl chain too.
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Last modified:
Feb 1, 2023
In our library since:
Nov 21, 2012
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12
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All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/1274
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| Edition name | Date |
|---|---|
| ZB-103161 | Feb 1, 2023 |
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