Design, synthesis, and biological evaluation of 16-substituted 4-azasteroids as tissue-selective androgen receptor modulators (SARMs).
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.
Mitchell
Helen J
HJ
Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 4, 770 Sumneytown Pike, West Point, Pennsylvania 19486, USA. Helen_mitchell2@merck.com
Dankulich
William P
WP
Hartman
George D
GD
Prueksaritanont
Thomayant
T
Schmidt
Azriel
A
Vogel
Robert L
RL
Bai
Chang
C
McElwee-Witmer
Sheila
S
Zhang
Hai Z
HZ
Chen
Fang
F
Leu
Chih-Tai
CT
Kimmel
Donald B
DB
Ray
William J
WJ
Nantermet
Pascale
P
Gentile
Michael A
MA
Duggan
Mark E
ME
Meissner
Robert S
RS
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
C410798:AR protein, human; D000728:Androgens; D001378:Azasteroids; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D011944:Receptors, Androgen