Annual Activities Report 2011 - INCT-Inofar - UFRJ

Annual Report 2011 | INCT-INOFAR
41
Highlights
Discovery of LASSBio-772, a
1,3-benzodioxole N-phenylpiperazine
derivative with potent alpha 1A/D-
Adrenergic receptor blocking
properties
Romeiro, L. A. S.; Ferreira, M. S.; DaSilva, L. L.; Castro, H. C.; Miranda, A. L. P.; Silva, C. L. M.; Noel,
F. G.; Nascimento, J. B.; Araujo, C. V.; Tibiriçá, E.; Barreiro, E. J.; Fraga, C. A. M. Eur. J. Med. Chem.
46 (2011) 3000-3012. DOI: 10.1016/j.ejmech.2011.04.032
The human adrenergic receptors are members of the G protein-coupled receptor superfamily that has
been extensively exploited as targets for a great number of drugs useful in the treatment of many different
diseases [1]. Alpha 1-AR subtypes, i.e. alpha 1A, alpha 1B, and alpha 1D have distinct pharmacology
and tissue expression, a fact relevant for the treatment of several diseases, such as hypertension and the
obstructive symptoms of the lower urinary tract, including the secondary urinary obstruction produced
by benign prostatic hyperplasia (BPH). Alternatively to surgical procedures, alpha 1-AR antagonists
are efficient to relief the obstructive symptoms of BPH by decreasing the prostatic muscular tonus,
mainly through the blockage of alpha 1A-AR. The drugs used for BPH treatment include the some
quinazoline derivatives, initially with prazosin and currently with terazosin, doxazosin and alfuzosin,
which are nonselective alpha 1-AR antagonists, so that hypotension triggered by alpha 1B-AR blockade
is their main adverse effect [2].
We described herein the discovery of 1-(2-(benzo[d]
[1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl)
piperazine (LASSBio-772) as a novel potent
and selective alpha 1A/1D adrenoceptor (AR)
antagonist.