Drug Sciences Department, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, 27100 Pavia, Italy.
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and Pharmaceutical Technologies Section, University of Palermo, 90100 Palermo, Italy.
Molecules. 2018 Mar 28;23(4):775. doi: 10.3390/molecules23040775.
Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-assisted solution phase synthesis (PASPS) and replacing reaction workup standard purification procedures with solid phase extraction (SPE). Specifically, the effects of solvent, such as dioxane, dimethylformamide (DMF), polyethylene glycol 400 (PEG 400), temperature, irradiation time, stoichiometric ratio of reagents, and catalysts (HCl, acetic acid, cerium ammonium nitrate (CAN)) were investigated to maximize both conversion and yield. The optimized protocol generally afforded the desired products in satisfying yields and purities. The designed library is a part of our current research on sigma 1 receptor modulators, a valuable tool for the identification of novel potential hit compounds.
化合物库是基于靶标的药物发现的重要要求。在本工作中，通过微波辅助有机合成（MAOS）与聚合物辅助溶液相合成（PASPS）相结合，并使用固相萃取（SPE）代替反应后处理标准纯化程序，制备了基于β-氨基酮骨架的小型聚焦化合物库。具体而言，考察了溶剂（如二恶烷、二甲基甲酰胺（DMF）、聚乙二醇 400（PEG 400））、温度、辐射时间、试剂和催化剂（HCl、乙酸、硝酸铈铵（CAN））的用量比对最大限度地提高转化率和产率的影响。优化后的方案通常以令人满意的收率和纯度得到所需产物。该设计的文库是我们当前研究σ1 受体调节剂的一部分，是鉴定新型潜在命中化合物的有用工具。
