Synthesis of potent, substituted carbazoles as selective androgen receptor modulators (SARMs)

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 24, 2010, Pages 7516-7520

  Miller, Chris P ^a   Bhaket, Pushpal ^b   Muthukaman, Nagarajan ^b   Lyttle, C Richard ^a   Shomali, Maysoun ^a   Gallacher, Kyla ^a   Slocum, Connie ^a   Hattersley, Gary ^a  

^a Radius Health Inc   (United States)

^b Sai Advantium Pharma Ltd   (India)

Author keywords

Androgen; Carbazole; Muscle; Prostate; SARM; Tetrahydrocarbazole

Indexed keywords

CARBAZOLE DERIVATIVE; RAD 35010; SELECTIVE ANDROGEN RECEPTOR MODULATOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CASTRATED MALE; CONTROLLED STUDY; DRUG BINDING; DRUG POTENCY; DRUG SYNTHESIS; IN VITRO STUDY; IN VIVO STUDY; LEVATOR ANI MUSCLE; MALE; NONHUMAN; PROSTATE; RAT;

ADMINISTRATION, ORAL; ANIMALS; CARBAZOLES; MALE; PROSTATE; RATS; RECEPTORS, ANDROGEN;

RATTUS;

EID: 78449274608     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.140     Document Type: Article

References (8)

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8. Immature Sprague-Dawley male rats were obtained Charles River Laboratories (Stoneridge, NY). All animals were maintained in a temperature and humidity controlled room with a 12 h light:12 h dark cycle, with ad lib access to food (TD 291615, Teklad, Madison, WI) and water. Rats were anesthetized and orchidectomized (GDX) or sham surgery (SHAM) was performed. After a seven-day recovery period, the animals were randomized according to weight and assigned to treatment groups (n = 5), SHAM, OVX + vehicle, OVX + Cpd treated. Testosterone propionate (TP 1 mg/kg in 5% DMSO/95% corn oil) was administered by once daily subcutaneous injections, while the compound was dosed in vehicle (0.5% carboxymethylcellulose) and administered by once daily oral gavage. The rats were then dosed once daily for four days. All animals were euthanized via carbon dioxide inhalation 24 h after the last dose. The prostate and levator ani bulba cavernous (LABC) tissues were removed, weighed and recorded.