<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml">The <italic>N</italic>-phenylpiperazine structures exhibit very extensive multiple receptor activities including the influencing of α1-adrenoceptors (α1-AR). Their antagonistic activity towards α1-AR is intensively applied in the therapy of cardiovascular system diseases - e. g. hypertension as well as in the treatment of benign prostatic hyperplasia. The limited ratio of selective effect on the specific subtypes of the α1-AR by certain drugs used in the practice (azosine-type structures) leads to multiple side effects which includes postural hypotension, syncope or first dose phenomena. The existence of multiple α1-AR subtypes holds promise for the discovery, projection and development of more specific selective drug molecules targeting only one α1-adrenoceptor subtype and making them free from side effects. Towards this aim wide-ranging modifications have been reported in the literature on the "basic" structure of the <italic>N</italic>-phenylpiperazine-based molecules. The present paper deals with the affinity features of (substituted) <italic>N</italic>-phenylpiperazines towards α1-ARs in which the structure is a connecting chain formed by (unsubstituted) ethane-1,2-diyl moiety bonded through certain atom or group (S, O, NH, NHCO-fragment, respectively) at the lipophilic part of the molecule.</abstract>

The N-phenylpiperazine structures exhibit very extensive multiple receptor activities including the influencing of α1-adrenoceptors (α1-AR). Their antagonistic activity towards α1-AR is intensively applied in the therapy of cardiovascular system diseases - e. g. hypertension as well as in the treatment of benign prostatic hyperplasia. The limited ratio of selective effect on the specific subtypes of the α1-AR by certain drugs used in the practice (azosine-type structures) leads to multiple side effects which includes postural hypotension, syncope or first dose phenomena. The existence of multiple α1-AR subtypes holds promise for the discovery, projection and development of more specific selective drug molecules targeting only one α1-adrenoceptor subtype and making them free from side effects. Towards this aim wide-ranging modifications have been reported in the literature on the "basic" structure of the N-phenylpiperazine-based molecules. The present paper deals with the affinity features of (substituted) N-phenylpiperazines towards α1-ARs in which the structure is a connecting chain formed by (unsubstituted) ethane-1,2-diyl moiety bonded through certain atom or group (S, O, NH, NHCO-fragment, respectively) at the lipophilic part of the molecule.

Relationship between chemical structure, binding affinity and selectivity towards α1-adrenoceptors in the group of substituted <italic>n</italic>-phenylpiperazines. Part 2*. compounds containing ethane-1,2-diyl connecting chain

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic

Institute of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic

European Pharmaceutical Journal

Relationship between chemical structure, binding affinity and selectivity towards α-adrenoceptors in the group of substituted -phenylpiperazines. Part 2. compounds containing ethane-1,2-diyl connecting chain

The N-phenylpiperazine structures exhibit very extensive multiple receptor activities including the influencing of α1-adrenoceptors (α1-AR). Their antagonistic...

Relationship between chemical structure, binding affinity and selectivity towards α₁-adrenoceptors in the group of substituted n-phenylpiperazines. Part 2^*. compounds containing ethane-1,2-diyl connecting chain

Publié en ligne: 25 nov. 2011

Pages: 42 - 55

DOI: https://doi.org/10.2478/v10219-011-0005-1

Mots clés
N-phenylpiperazines, α-adrenoceptors, affinity, selectivity

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Relationship between chemical structure, binding affinity and selectivity towards α1-adrenoceptors in the group of substituted n-phenylpiperazines. Part 2*. compounds containing ethane-1,2-diyl connecting chain