Design and synthesis of new steroidal inhibitors of estrogen synthase (aromatase)

• Published in: Lipids 2000-03, Vol.35 (3), p.271-277
• Main Authors: Parish, Edward J., Li, Shengrong, Rao, Zhigang
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Aromatase Inhibitors; Biosynthesis; Breast cancer; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Estrogens; Hormones; Humans; Indicators and Reagents; Inhibitors; Steroids - chemical synthesis; Steroids - chemistry; Steroids - pharmacology; Structure-Activity Relationship
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-000-0523-0

The estrogen synthase (aromatase) enzyme system is responsible for the biosynthesis of estrogen hormones in human females. Estrogens are vital for normal growth and development, but will promote the growth of certain breast cancers. Appromaximately 30–50% of breast cancers are considered to be hormone‐dependent. Consequently regulation of estrogen biosynthesis has advanced as a potential therapeutic strategy. This has led to the development of active‐site inhibitors, which may have potential for the control of breast cancer. We have recently prepared a number of new steroidal inhibitors that have been evaluated as aromatase inhibitors. These include steroidal A/B‐ring isoxazoles and a series of A/B‐ring pyrazoles with alkyl‐ and aryl‐substituted nitrogen. In addition, we have developed new chemical procedures for the synthesis of 6β‐hydroxy steroids, which could be key intermediates in the preparation of C‐19 inhibitors of aromatase activity.