Discovery of a novel series of nonsteroidal androgen receptor modulators: 5- or 6-oxachrysen-2-ones.
A novel oxachrysenone series (2) of nonsteroidal selective androgen receptor modulators (SARM) was developed based on the 6-aryl-2-quinolinones (1). Synthesis and preliminary SAR results based on in vitro assays are discussed. In the cotransfection assay, lead compound 5d showed AR agonist activity more potent than dihydrotestosterone (DHT), whereas compound 17b was a potent antagonist similar to bicalutamide.
Zhao
Shuo
S
Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, CA 92121, USA. szhao2005@gmail.com
Shen
Yixing
Y
van Oeveren
Arjan
A
Marschke
Keith B
KB
Zhi
Lin
L
D000728:Androgens; D000813:Anilides / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009570:Nitriles / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000494:pharmacology*
D000728:Androgens; D000813:Anilides; D006576:Heterocyclic Compounds, 4 or More Rings; D009570:Nitriles; D015363:Quinolones; D014105:Tosyl Compounds; C053541:bicalutamide