(Arylpiperazinyl)cyclohexylsufonamides: discovery of alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS).

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Chiu G, Li S, Connolly PJ, Pulito V, Liu J, Middleton SA

(Arylpiperazinyl)cyclohexylsufonamides: discovery of alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS).

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3292-7. Epub 2007 Apr 10.

PubMed ID
17452102 [ View in PubMed
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Abstract

Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1) blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TamsulosinAlpha-1A adrenergic receptorKi (nM)0.19N/AN/ADetails
TamsulosinAlpha-1B adrenergic receptorKi (nM)2N/AN/ADetails
TamsulosinAlpha-1D adrenergic receptorKi (nM)0.2N/AN/ADetails