Eklund Julia, Bremberg Ulf, Larsson Jessica, Torkelsson Edvard, Wennerberg Johan, Zandelin Symantha, Odell Luke R
Department of Medicinal Chemistry, Uppsala University, Box-574, Uppsala SE-751 23, Sweden.
Red Glead Discovery, Medicon Village, Lund SE-223 81, Sweden.
J Med Chem. 2025 Apr 10;68(7):7153-7165. doi: 10.1021/acs.jmedchem.4c02612. Epub 2025 Mar 20.
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability, rapid metabolic conversion to psilocin, and easy synthesis, with potential advantages over psilocybin. This research introduces viable options through psilocin ester compounds and psilocin salts, offering promising avenues for future development.
随着使用裸盖菇素疗法治疗精神健康障碍的兴趣日益浓厚，高效生产方法的需求变得越来越重要。目前医用级裸盖菇素的生产效率低下，依赖于复杂的多步合成。本研究探索并评估了裸盖菇酚酯前药和裸盖菇酚盐作为裸盖菇素的潜在替代品，重点关注它们的合成简便性、化学稳定性和代谢特征。合成并评估了一个包含15种裸盖菇酚酯前药和6种裸盖菇酚盐的多样文库。该研究成功鉴定出几种具有理想特性的裸盖菇酚酯前药和裸盖菇酚盐，包括储存和处理稳定性、快速代谢转化为裸盖菇酚以及合成简便，与裸盖菇素相比具有潜在优势。这项研究通过裸盖菇酚酯化合物和裸盖菇酚盐引入了可行的选择，为未来发展提供了有希望的途径。
