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cc-by (c)  Bagán, A. et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222508

Synthesis of Diversely Substituted Diethyl (Pyrrolidin-2-Yl)Phosphonates

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Imidazoline I2 receptors (I2-IR) are untapped therapeutic targets lacking a structuraldescription. Although the levels of I2-IR are dysregulated in a plethora of illnesses,the arsenal of ligands that can modulate I2-IR is limited. In this framework, we havereported several new structural families embodying the iminophosphonate functionalgroup that have an excellent affinity and selectivity for I2-IR, and selected members havedemonstrated relevant pharmacological properties in murine models of neurodegenerationand Alzheimer’s disease. Starting with these iminophosphonates, we continued to exploittheir high degree of functionalization through a short and efficient synthesis to access unprecedented2,3-di, 2,2,3-tri, 2,3,4-tri, and 2,2,3,4-tetrasubstituted diethyl (pyrrolidine-2-yl)phosphonates. The stereochemistry of the new compounds was unequivocally characterizedby X-ray crystallographic analyses. Two selected compounds with structural featuresshared with the starting products were pharmacologically evaluated, allowing us to deducethe required key structural motifs for biologically active aminophosphonate derivatives.

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BAGAN POLONIO, Andrea, LÓPEZ-RUIZ, Alba, ABÁS PRADES, Sònia, MOLINS I GRAU, Elies, PÉREZ, Belén, MUNETA-ARRATE, Itziar, CALLADO, Luis f., ESCOLANO MIRÓN, Carmen. Synthesis of Diversely Substituted Diethyl (Pyrrolidin-2-Yl)Phosphonates. _Molecules_. 2025. Vol. 30, núm. 2078. [consulta: 3 de gener de 2026]. ISSN: 1420-3049. [Disponible a: https://hdl.handle.net/2445/222508]

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