Novel non-steroidal/non-anilide type androgen antagonists with an isoxazolone moiety

3-Substitutcd (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. (C) 2002 Elsevier Science Ltd. All rights reserved.