A bioisosteric approach to the discovery of indole carbinol androgen receptor ligands.
Two potential bioisosteres of the nonsteroidal antiandrogen bicalutamide, an imidazolidinone and an indole, were synthesized and tested for their androgen receptor binding. Indole was discovered to be a suitable bioisostere for the acyl anilide moiety in the parent compound. Several analogs in the indole series were found to be 10-fold better than bicalutamide in binding to the recombinant androgen receptor binding domain.
Lanter
James C
JC
Johnson and Johnson Pharmaceutical Research and Development L.L.C., 1000 Route 202 S, Raritan, NJ 08869, USA. jlanter@prdus.jnj.com
Fiordeliso
James J
JJ
Allan
George F
GF
Musto
Amy
A
Hahn
Do Won
do W
Sui
Zhihua
Z
D000818:Animals; D007211:Indoles / Q000378:metabolism*; D008024:Ligands; D000432:Methanol / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007211:Indoles; D008024:Ligands; D011944:Receptors, Androgen; D000432:Methanol