[2.2.1]-Bicyclic sultams as potent androgen receptor antagonists.
This letter describes the discovery, synthesis, SAR, and biological activity of [2.2.1]-bicyclic sultams as potent antagonists of the androgen receptor. Optimization of the series led to the identification of compound 25, which displayed robust pharmacodynamic effects in rats after oral dosing.
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States. Electronic address: weifang.shan@bms.com.
Weifang
W
Shan
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Aaron
A
Balog
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Andrew
A
Nation
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Xiao
X
Zhu
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Jing
J
Chen
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Mary Ellen
ME
Cvijic
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Jieping
J
Geng
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Cheryl A
CA
Rizzo
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Thomas
T
Spires
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Ricardo M
RM
Attar
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Mary
M
Obermeier
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Sarah
S
Traeger
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Jun
J
Dai
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Yingru
Y
Zhang
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Michael
M
Galella
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
George
G
Trainor
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Gregory D
GD
Vite
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States.
Ashvinikumar V
AV
Gavai
D000284:Administration, Oral; D059002:Androgen Receptor Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008958:Models, Molecular; D009282:Naphthalenesulfonates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D013329:Structure-Activity Relationship
D059002:Androgen Receptor Antagonists; D001643:Bridged Bicyclo Compounds; D009282:Naphthalenesulfonates; D011944:Receptors, Androgen; C016768:naphthosultone
Androgen receptor antagonist; Cancer; Nuclear hormone receptor; Pharmacokinetics and pharmacodynamics