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Updated: Sep 4, 2026

Interactive Molecular Model Assembly with 3D Printing
Published on: August 13, 2020
Modular assembly and property profiling of an expansive, shape-defined library of pentacyclic saturated
Elia Boschi1, Dmitry Mazunin2, Alex Mueller2
1Laboratory for Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich Zürich 8093 Switzerland bode@org.chem.ethz.ch.
Abstract:
Small-molecule drug discovery is increasingly applied to targets historically classified as "undruggable", such as non-coding RNAs and biomolecular interactions. These complex interfaces demand ligands with greater three-dimensional complexity and preferred physicochemical profiles that are deficient in typical small molecule chemical libraries housed in large pharmaceutical companies or commercial suppliers. Inspired by the need for novel libraries that might hypothetically address these target classes, we report the design, iterative synthesis, and comprehensive property profiling of a novel chemical library of shape-defined, morpholine-containing pentacycles. Utilizing iterative Stannyl Amine Protocol (iSnAP) reagents, we divergently assembled rigid, 3D-diverse scaffolds that exhibit a chameleonic basic character at physiological pH, elegantly balancing aqueous solubility with membrane permeability. Computational analysis of the 2400-member virtual library confirmed that it occupies a distinct, three-dimensional chemical space. Furthermore, high-throughput experimental profiling of the synthesized compounds revealed promising drug-like properties, including broad aqueous solubility, metabolic stability, low cytochrome P450 inhibition, and tunable membrane permeability. Although no bioactivity has yet been discovered from this library, the compounds offer a robust chemical foundation for future evaluations in ligand screenings targeting emerging therapeutic modalities.
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