What is the main therapeuti use of Androgens?
Promoting anabolism, for example following trauma (also used as supplementation in aging, genetic deficits). Androgens also are masculinizing; in most cases this represents an unwanted side effect
What is the main goal in Androgen drug design?
Optimize anabolic effects while minimizing masculinizing effects. A secondary goal is to create an orally active formulation
What are the SARs of Androgens?
1) C3 keto required; de-keto as prodrugs. 2) C17 has a Beta -OH side chain. 3) C4=C5 bond is inhibitory. 4) Otherwise, many modifications are tolerated (can remove C19 methyl group to make "nor" form with higher anabolic activity
What is the primary endogenous Androgen?
Testosterone (C17 OH and C3 =O)
What can be done to make an orally active Androgen?
The catabolic blocking of C17 alpha-methyl creates an orally active form
What can be done to make an Androgen a prodrug?
C17 acetoxy makes it a prodrug
What are Steroid 5 alpha-Reductase (SRD5A) Inhibitors?
SRD5A: main enzyme converting testosterone to its active form DHT. Required by prostate cancer cells to retain transformed (cancerous) state. SRD5A inhibitors block prostate cancer (at least for a while)
What is a common SRD5A inhibitor?