Design, synthesis, and biological evaluation of 16-substituted 4-azasteroids as tissue-Selective Androgen Receptor Modulators (SARMs)

Journal of Medicinal Chemistry

Volumn 52, Issue 15, 2009, Pages 4578-4581

  Mitchell, Helen J ^a   Dankulich, William P ^a   Hartman, George D ^a   Prueksaritanont, Thomayant ^a   Schmidt, Azriel ^a   Vogel, Robert L ^a   Bai, Chang ^a   McElwee Witmer, Sheila ^a   Zhang, Hai Z ^a   Chen, Fang ^a   Leu, Chih Tai ^a   Kimmel, Donald B ^a   Ray, William J ^a   Nantermet, Pascale ^a   Gentile, Michael A ^a   Duggan, Mark E ^a,b   Meissner, Robert S ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Link Medicine Corporation

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANOLONE; AZASTEROID; SELECTIVE ANDROGEN RECEPTOR MODULATOR;

ANIMAL EXPERIMENT; ARTICLE; DOG; DRUG ACTIVITY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; FEMALE; IN VITRO STUDY; MALE; NONHUMAN; ORCHIECTOMY; OVARIECTOMY; RAT;

ANIMALS; AZASTEROIDS; DOGS; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; FEMALE; HUMANS; MALE; ORGAN SPECIFICITY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ANDROGEN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68549107837     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900880r     Document Type: Article

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25. In humans and rats, most of the hormonal bone resorption activity is controlled by ERR and not by AR. The OVX rats used in this experiment may have high bone turnover, and therefore, an anti-resorptive agent was used to suppress bone resorption in order to increase the assay window. The effects of SARMs on cortical bone formation with and without an antiresorptive agent were compared (to be reported elsewhere).
26. Other administration routes were also used. Compound 24 gave similar in vivo effects when dosed orally from a 0.5% aqueous methylcellulose suspension.