(Phenylpiperidinyl)cyclohexylsulfonamides: development of alpha1a/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

(Phenylpiperidinyl)cyclohexylsulfonamides: development of alpha1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3930-4. Epub 2007 May 3.

PubMed ID
17517507 [ View in PubMed
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Abstract

Although alpha(1) adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by the subtype non-selective nature of the current drugs. To overcome this problem, it was hypothesized that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the therapy of BPH/LUTS. In developing such selective alpha(1a/1d) ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has been synthesized and evaluated for binding to three cloned human alpha(1)-adrenergic receptor subtypes. Many compounds showed equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity versus the alpha(1b) subtype.

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