Object
Title: Studies on bupranolol and its analogues
Abstract:
The introduction to this thesis presented the historical view of the low affinity site of β1-adrenergic receptors (β1L-AR). The main pharmacological tools, that are usedto characterize this subtype of receptor, as well as the importance of the chirality of drugs were described. Since enantiomers of BUP are not commercially available, the main purpose of this thesis was to develop a method of obtaining (S)-(-)-BUP, the most active known antagonist of the β1L-AR. (S)-(-)-BUP was synthetized beginning with chiral epichlorohydrin with enantiomeric excess (ee) higher than 99%. For the economical reason, different approaches to get (S)-BUP were also proposed, with the use of microorganisms or enzymes. The screening and the optimization of the conditions were performed, to finally obtain (S)-BUP with ee 96%. The second aim of this thesis was to synthetize active racemic or nonracemic analogues of BUP. The conditions of HPLC analysis of nonracemic compounds with the chiral column were developed. Obtained compounds were pharmacologically examined under in vivo conditions using pithed rat model. It was investigated whether the β1L-adrenoceptors were influenced by racemic analogues of BUP, and whether the stereoselectivity extended also to the other compounds. In order to have an independent estimation of the activity and affinity of the drugs for the β1L-adrenoceptor, active compounds we ; re studied in the same model as well as the affinities were determined in rat brain cortex membranes. Additionally, the lipophilicity of racemic compounds was estimated with the use of RP TLC and in silico methods.
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Last modified:
Mar 17, 2023
In our library since:
Mar 11, 2013
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18
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http://dl.cm-uj.krakow.pl:8080/publication/3481
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| Edition name | Date |
|---|---|
| ZB-117132 | Mar 17, 2023 |
