Design and synthesis of an alpha1a-adrenergic receptor subtype-selective antagonist from BE2254.
An alpha1a-adrenoceptor-selective antagonist has the potential to be a new benign prostatic hyperplasia drug with reduced side-effects. Modification of the non-selective antagonist BE2254 led to the development of a series of tetralin analogs. Evaluation of these compounds in cloned human alpha1-adrenoceptors resulted in the discovery of an analog that showed selectivity toward the human alpha1a-adrenergic receptor subtype. The compound also showed moderate potency to block human prostate muscle contraction.
Chiu
George
G
Lundbeck Research USA, Inc., 215 College Road, Paramus, NJ 07652, USA. georgechiu140@yahoo.com
Gluchowski
Charles
C
Forray
Carlos
C
D018674:Adrenergic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011467:Prostate / Q000187:drug effects / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D013379:Substrate Specificity; D013764:Tetrahydronaphthalenes / Q000737:chemistry
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D013764:Tetrahydronaphthalenes; C095210:tetralin