Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)

Journal of Medicinal Chemistry

Volumn 53, Issue 7, 2010, Pages 2779-2796

  Jung, Michael E ^a   Ouk, Samedy ^a   Yoo, Dongwon ^a   Sawyers, Charles L ^a,b   Chen, Charlie ^a   Tran, Chris ^a   Wongvipat, John ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAZIDOBUTANE; 2 (4 AZIDOBUTYLAMINO) 2 METHYLPROPIONITRILE; 2 (4 HYDROXYPHENYLAMINO) 2 METHYLPROPANENITRILE; 2 METHYL 2 (4 METHYLPHENYL)AMINOPROPANE NITRILE; 2 METHYL 2 PHENYLAMINOPROPANENITRILE; 4 [3 (3 AZIDOPROPYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 AZIDOBUTYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 AZIDOBUTYL) 5 IMINO 4,4 DIMETHYL 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 HYDROXYPHENYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 HYDROXYPHENYL) 5 IMINO 4,4 DIMETHYL 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 METHYLPHENYL) 4 ETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 METHYLPHENYL) 4 METHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 METHYLPHENYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (4 METHYLPHENYL) 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (5 AZIDOPENTYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (6 AZIDOHEXYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 (7 AZIDOHEPTYL) 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 [3 PHENYL 4,4 DIMETHYL 5 OXO 2 THIOXOIMIDAZOLIDIN 1 YL] 2 TRIFLUOROMETHYLBENZONITRILE; 4 AZIDOBUTYLAMINE; 4 ISOTHIOCYANATO 2 TRIFLUOROMETHYLBENZONITRILE; ANDROGEN RECEPTOR; BICALUTAMIDE; FLUTAMIDE; HORMONE ANTAGONIST; HYDROXYFLUTAMIDE; MDV 3100; N(4 CYANO 3 TRIFLUOROMETHYLPHENYL) N' (4 METHYLPHENYL)THIOUREA; NILUTAMIDE; RU 59063; THIOHYDANTOIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CASTRATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; PROSTATE CANCER; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE, TUMOR; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION, NEOPLASTIC; MALE; ORCHIECTOMY; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN; STRUCTURE-ACTIVITY RELATIONSHIP; THIOHYDANTOINS; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77950574393     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901488g     Document Type: Article

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19. 3, they are randomized into five groups. Each group has six animals. After they reach this tumor volume, they are given orally either vehicle or 91 at 0.1, 1, and 10 mg/kg everyday. The tumors are measured three-dimensionally, width, length and depth, using a caliper.
20. LNCaP in 10% FBS, split on day 1, add drugs on day 5, harvest on day 6 and day 10 for PSA.