Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives.
A series of arylpiperazine derivatives were prepared and evaluated for their alpha1-adrenoceptor antagonistic activities and 5alpha-reductase inhibitory activities. SAR study led to the identification of the potent dual-acting compound 2f, which had a pA2 value of 7.5 for alpha1-adrenoceptor antagonism and an IC50 value of 1.5 nM for 5alpha-reductase inhibition.
Sato
H
H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Kitagawa
O
O
Aida
Y
Y
Chikazawa
J
J
Kurimoto
T
T
Takei
M
M
Fukuta
Y
Y
Yoshida
K
K
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D008956:Models, Chemical; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000494:pharmacology; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D011467:Prostate / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D000077489:Piperazine; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase