Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives

H Sato; O Kitagawa; Y Aida; J Chikazawa; T Kurimoto; M Takei; Y Fukuta; K Yoshida

doi:10.1016/s0960-894x(99)00230-9

Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives

Bioorg Med Chem Lett. 1999 Jun 7;9(11):1553-8. doi: 10.1016/s0960-894x(99)00230-9.

Authors

H Sato¹, O Kitagawa, Y Aida, J Chikazawa, T Kurimoto, M Takei, Y Fukuta, K Yoshida

Affiliation

¹ Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.

PMID: 10386934
DOI: 10.1016/s0960-894x(99)00230-9

Abstract

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.

MeSH terms

Adrenergic alpha-Antagonists / chemical synthesis*
Adrenergic alpha-Antagonists / pharmacology
Animals
Cholestenone 5 alpha-Reductase
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Male
Models, Chemical
Oxidoreductases / antagonists & inhibitors*
Oxidoreductases / chemical synthesis*
Oxidoreductases / pharmacology
Piperazine
Piperazines / chemistry*
Prostate / drug effects
Rabbits
Rats
Rats, Sprague-Dawley

Substances

Adrenergic alpha-Antagonists
Piperazines
Piperazine
Oxidoreductases
Cholestenone 5 alpha-Reductase