Synthesis and SAR of potent and selective androgen receptor antagonists: 5,6-Dichloro-benzimidazole derivatives.
The synthesis and in vivo SAR of 5,6-dichloro-benzimidazole derivatives as novel selective androgen receptor antagonists are described. During screening of 2-alkyl benzimidazoles, it was found that a trifluoromethyl group greatly enhances antagonist activity in the prostate. Benzimidazole 1 is a potent AR antagonist in the rat prostate (ID50 = 0.15 mg/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
Linton
Olivia
O
Lundeen
Scott G
SG
Sui
Zhihua
Z
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D008970:Molecular Weight; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis; D013450:Sulfones / Q000138:chemical synthesis
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D001562:Benzimidazoles; D007202:Indicators and Reagents; D013440:Sulfides; D013450:Sulfones