Synthesis and structure-activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor.
Basic Information
ID: ALA3867431
Journal: Eur J Med Chem
Title: Synthesis and structure-activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor.
Authors: Silva RO, de Oliveira AS, Nunes Lemes LF, de Camargo Nascente L, Coelho do Nascimento Nogueira P, Silveira ER, Brand GD, Vistoli G, Cilia A, Poggesi E, Buccioni M, Marucci G, Bolognesi ML, Romeiro LAS.
Abstract: Arylpiperazines 2-11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar pKi of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application.
CiteXplore: 27448917
DOI: 10.1016/j.ejmech.2016.06.052
Patent ID: ┄