Abstract
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.
Highlights
Identifying hit compounds is the first step in the complex drug-discovery process, and the degree of structural diversity is an important element, enhancing the rate of success in finding a potential lead candidate
A small focused library of 36 β-amino ketones derived from the coupling of aryl-ketones 1–6 with amines a–f (Figure 3) was prepared
According to data in the literature concerning the different reactivities of secondary amines related to their structures and experimental conditions in the Mannich reaction [25,35], we set up a novel protocol using the cyclic and acyclic amines a and b as “building block” models
Summary
Identifying hit compounds is the first step in the complex drug-discovery process, and the degree of structural diversity is an important element, enhancing the rate of success in finding a potential lead candidate. In this context, β-amino carbonyl compounds represent a class of important pharmacophores and useful building blocks for the synthesis of diverse classes of biologically active molecules [1,2]. Β-amino ketones can be key intermediates for the synthesis of pharmaceutically relevant compounds [18,19].
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