Steroidal silicon side-chain analogues as potential antifertility agents

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Ethynylestradiol is a widely used synthetic estrogen.
• Modifying ethynylestradiol's structure can alter its biological activity.
• Developing compounds with selective estrogenic effects is a key research area.

Purpose of the Study:

• To synthesize novel silicon-substituted ethynylestradiol analogues.
• To evaluate the antifertility and estrogenic activities of these analogues.
• To explore the structure-activity relationships of these compounds.

Main Methods:

• Synthesis of silicon-substituted ethynylestradiol analogues.
• Antifertility and estrogenic activity assays in rats.
• Structure-activity relationship analysis based on van der Waals volumes.

Main Results:

• Several [(trialkylsilyl)ethynyl]estradiol analogues were successfully synthesized.
• Compounds 17 alpha-[(triethylsilyl)ethynyl]estradiol and 17 alpha-[(tert-butyldimethylsilyl)ethynyl]estradiol demonstrated high antifertility potency.
• These compounds exhibited markedly reduced estrogenic activity compared to ethynylestradiol.
• A correlation was observed between biological activity and the van der Waals volumes of silicon substituents.

Conclusions:

• Silicon substitution can effectively modify the biological activity of ethynylestradiol.
• Novel analogues show a promising separation of antifertility from estrogenic activity.
• These findings contribute to the development of selective estrogen receptor modulators.