Molecular design and synthesis of 1,4-disubstituted piperazines as α1-adrenergic receptor blockers

A new series of 4,5,6,7-tetrahydrothieno[2,3-c] pyridine-3-carboxylic acid amide and 3,5,6,8-tetrahydro-pyrido[40,30: 4,5] thieno[2,3-d] pyrimidin-4-one derivatives were designed, synthesized, their binding nd functional properties as alpha(1)-adrenoreceptors blockers were evaluated. A new validated alpha(1)-adrenoreceptor blocker pharmacophore model ( hypothesis) was generated using Discovery Studio 2.5. The compare-fit study for the designed molecules with the generated hypothesis was fulfilled and several compounds showed significant high fit values. Compounds IVa-c, VIIa-d, VIIIa-c, Xa-c, XIa-d have shown blocking activity ranging from 46.73% up to 94.74% compared to 99.17% for prazosin. (C) 2014 Elsevier Inc. All rights reserved.