24 Sex Steroids: Testosterone (Androgens)

Question 1

What is the main therapeuti use of Androgens?

Answer 1

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

Question 2

What is the main goal in Androgen drug design?

Answer 2

Optimize anabolic effects while minimizing masculinizing effects. A secondary goal is to create an orally active formulation

Question 3

What are the SARs of Androgens?

Answer 3

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

Question 4

What is the primary endogenous Androgen?

Answer 4

Testosterone (C17 OH and C3 =O)

Question 5

What can be done to make an orally active Androgen?

Answer 5

The catabolic blocking of C17 alpha-methyl creates an orally active form

Question 6

What can be done to make an Androgen a prodrug?

Answer 6

C17 acetoxy makes it a prodrug

Question 7

What are Steroid 5 alpha-Reductase (SRD5A) Inhibitors?

Answer 7

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)

Question 8

What is a common SRD5A inhibitor?

Answer 8

Finasteride