4-Alkyl- and 3,4-dialkyl-1,2,3,4-tetrahydro-8-pyridono[5,6-g]quinolines: potent, nonsteroidal androgen receptor agonists.
A series of human androgen receptor (hAR) agonists based on 4-alkyl-; 4,4-dialkyl-; and 3,4-dialkyl-1,2,3,4-tetrahydro-8-pyridono[5,6-g]quinoline was synthesized and evaluated in competitive receptor binding assays and an androgen receptor cotransfection assay in a mammalian cell background. A number of compounds in this series demonstrated activity equal to or better than dihydrotestosterone in both assays and represent a novel class of compounds for use in androgen replacement therapy.
Higuchi
R I
RI
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Edwards
J P
JP
Caferro
T R
TR
Ringgenberg
J D
JD
Kong
J W
JW
Hamann
L G
LG
Arienti
K L
KL
Marschke
K B
KB
Davis
R L
RL
Farmer
L J
LJ
Jones
T K
TK
D000728:Androgens; D000818:Animals; D019556:COS Cells; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D011485:Protein Binding; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*
D000728:Androgens; D015363:Quinolones; D013196:Dihydrotestosterone