17alkylation

17-alkylation is a chemical modification of steroid molecules in which an alkyl group is introduced at the carbon 17 position, most commonly the 17α position. This alteration is used to produce steroids that are active when taken by mouth by reducing hepatic first-pass metabolism, allowing oral administration and longer duration of action.

Chemistry and scope: The 17α-alkyl group is typically a methyl or ethyl substituent. The modification can be made during the chemical synthesis of a steroid nucleus, and it is most associated with anabolic steroids, though modifications of other steroid classes have occurred. The change can affect the compound’s receptor affinity, metabolism, and pharmacokinetic properties.

Pharmacology and use: 17α-alkylated steroids are designed to be orally bioavailable and to maintain activity after ingestion. Historically they were used as oral agents for testosterone deficiency and, in some cases, for anabolic purposes. Examples commonly cited in pharmacology and medical history include methyltestosterone and methandrostenolone (Dianabol). While oral activity is increased, these compounds are associated with greater risk of liver-related adverse effects compared with non-17α-alkylated steroids.

Safety and regulation: Prolonged use of 17α-alkylated steroids can cause hepatotoxicity, cholestasis, and other liver abnormalities. Because of safety concerns and potential for abuse, many such compounds are tightly regulated or prohibited for performance enhancement in sports and are prescribed under strict medical supervision when indicated.

History and notes: The development of 17α-alkylated steroids in the mid- to late 20th century significantly impacted oral steroid therapies but also spurred regulatory and safety measures due to hepatic risks.