Arylpiperazines with affinity toward alpha(1)-adrenergic receptors.
In the last years, alpha(1) adrenoceptors (alpha(1)-AR) have been the subject of intense research, in part because receptor-binding studies and molecular biology have opened up new aspects of understanding but also because of the potential to find new drugs possibly acting toward pathophysiological processes where alpha(1)-AR are involved, such as benign prostatic hyperplasia (BPH) or hypertension. At present, arylpiperazines represent one of the most studied classes of molecules with affinity at alpha(1)-AR. In fact, a large amount of work has been done and reported, describing synthetic procedures, biological evaluation at both alpha(1)-AR and the corresponding subtypes, and structure-activity relationships (SARs). In this paper, a review based on a literature survey aimed at focusing on the structural properties that a compound should possess to show affinity toward alpha(1)-AR is presented. Moreover, the identification and optimization of the structural features of a hit compound derived from a pharmacophore-based database search, leading to a new class of arylpiperazinylalkyl pyridazinone derivatives with alpha(1)-AR affinity is reported.
Manetti
F
F
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Aldo Moro, Italy. manettif@unisi.it
Corelli
F
F
Strappaghetti
G
G
Botta
M
M
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013329:Structure-Activity Relationship
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1