title: Design, synthesis, and biological evaluation of 16-substituted 4-azasteroids as tissue-selective androgen receptor modulators (SARMs).
abstract: A novel series of 16-substituted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential, and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in the OVX and ORX rat models and exhibited an osteoanabolic, tissue-selective profile.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 4, 770 Sumneytown Pike, West Point, Pennsylvania 19486, USA. Helen_mitchell2@merck.com
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mitchell
authors.forename: William P
authors.initials: WP
authors.lastname: Dankulich
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.forename: Azriel
authors.initials: A
authors.lastname: Schmidt
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vogel
authors.forename: Chang
authors.initials: C
authors.lastname: Bai
authors.forename: Sheila
authors.initials: S
authors.lastname: McElwee-Witmer
authors.forename: Hai Z
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Leu
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kimmel
authors.forename: William J
authors.initials: WJ
authors.lastname: Ray
authors.forename: Pascale
authors.initials: P
authors.lastname: Nantermet
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gentile
authors.forename: Mark E
authors.initials: ME
authors.lastname: Duggan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Meissner
mesh_terms: D000728:Androgens; D000818:Animals; D001378:Azasteroids / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D015195:Drug Design; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C410798:AR protein, human; D000728:Androgens; D001378:Azasteroids; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D011944:Receptors, Androgen