2-(2,2,2-Trifluoroethyl)-5,6-dichlorobenzimidazole derivatives as potent androgen receptor antagonists.
The synthesis and in vivo SAR of N-benzyl, N-aceto, and N-ethylene ether derivatives of 2-(2,2,2-trifluoroethyl)-5,6-dichloro-benzimidazole as novel androgen receptor antagonists are described. SAR studies led to the discovery of 4-bromo-benzyl benzimidazole 17 as a more potent androgen receptor antagonist in the rat prostate (ID(50)=0.13mg/day), compared with bicalutamide (ID(50)=0.23mg/day).
Ng
Raymond A
RA
Johnson & Johnson Pharmaceutical Research and Development, LLC, Drug Discovery, 665 Stockton Drive, Exton, PA 19341, USA.
Guan
Jihua
J
Alford
Vernon C
VC
Lanter
James C
JC
Allan
George F
GF
Sbriscia
Tifanie
T
Lundeen
Scott G
SG
Sui
Zhihua
Z
D000478:Alkylation; D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000494:pharmacology
C518726:2-(2,2,2-trifluoroethyl)-5,6-dichlorobenzimidazole; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D001562:Benzimidazoles; D007202:Indicators and Reagents; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide