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Poszukiwanie nowych selektywnych antagonistów receptorów α1 adrenergicznych

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Malawska B. , Kulig K.

Wiadomości Chemiczne

2003

tom [Z] 57, 3-4

267--288

α1,-Adrenergic receptors (α1-AR) are members of the superfamily of G protein coupled receptors that transduce signals across the cell membrane. α1-ARs are comprised of multiple subtypes that have been identified by both pharmacological and binding studies [1], To date, they are classified into α1A, α1B, and α1D and the corresponding cloned counterparts termed α1a, α1b, and α1dAR, respectively. These subtypes have different tissue distributions with the α1A receptors predominating in lower urinary tract tissue, whereas this receptor subtype is less prevalent in the vasculature [2-4]. In recent years, the search for new selective α1-AR antagonists has intensified, due to their importance in the treatment of hypertension and of benign prostatic hyperplasia (BPH) [5-7]. Tamsulosin, the first α1A-AR „selective” antagonists for the treatment of BPH, was approved in 1997 [9, 12], A number of α1A subtype selective antagonists representing different structural classes of compounds were disclosed recently. These include: quinazolines [8-13], phenylalkylamines [9, 12, 14], piperidines [9, 15-23], arylpiperazines [24-36] and related compounds [37, 38], A review on the development of α1, selective antagonists are presented.