Novel non-steroidal/non-anilide type androgen antagonists with an isoxazolone moiety.
3-Substituted (Z)-4-(4-N,N-dialkylaminophenylmethylene)-5(4H)-isoxazolones and related compounds were designed and prepared as candidates for structurally novel androgen antagonists. Several compounds showed potent anti-androgenic activity as assessed by nuclear androgen receptor binding assay and growth inhibition assay using androgen-dependent Shionogi carcinoma cells SC-3. They were approximately 10--220 times more potent than flutamide in these assay systems. They also showed anti-androgenic activity toward prostate tumor cell line LNCaP, which has an aberrant nuclear androgen receptor.
Ishioka
Toshiyasu
T
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Kubo
Asako
A
Koiso
Yukiko
Y
Nagasawa
Kazuo
K
Itai
Akiko
A
Hashimoto
Yuichi
Y
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000726:Androgen Antagonists; D007555:Isoxazoles; D011944:Receptors, Androgen; D013739:Testosterone