History of Cortisone and Related Compounds

Abstract

Abstract Steroidal hormones were isolated from the adrenal cortex in the 1930s and were synthesised a decade later. Several of these structures have highly effective anti‐inflammatory activity but also exhibit serious side effects. Chemical analogues have now been discovered with better activity and reduced side effects. Such agents are administered for the treatment of a wide range of inflammatory conditions, including rheumatoid arthritis and asthma. Anti‐inflammatory activity can be improved by introducing functional groups or substituents at key positions of the steroid structure. Similarly, substituents placed at key positions can reduce side effects and metabolic susceptibility. Nevertheless, there are still risks associated with the long‐term use of steroids, and research is currently looking at novel agents that will act locally at the site of administration and are rapidly metabolised to inactive compounds once they reach the blood supply. Key Concepts: Adrenocorticoids are released by the adrenal glands and can be classified as glucocorticoids or mineralocorticoids. Cortisone, hydrocortisone and corticosterone are examples of glucocorticoids. Cortisone was isolated in the late 1930s, and a synthesis was devised in 1948. The beneficial anti‐inflammatory effects of cortisone on patients with rheumatoid arthritis were demonstrated in the late 1940s. Glucocorticoids have important effects on cell metabolism and are released as a result of stress. Several glucocorticoids have anti‐inflammatory activity making them useful in the treatment of conditions such as skin and mucosal inflammations, rheumatoid arthritis and asthma. Endogenous glucocorticoids such as cortisol and cortisone are used in the clinic but suffer from side effects. Analogues of cortisone and cortisol have been developed that have improved anti‐inflammatory activity and reduced side effects. Key structural features have been identified that can be introduced to the steroid structure in order to increase anti‐inflammatory activity and absorption, while decreasing side effects and metabolism. Soft drugs have been developed since the 1970s, which act locally at the site of administration and are rapidly metabolised should they reach the blood supply.