Synthesis of Diversely Substituted Diethyl (Pyrrolidin-2-Yl)Phosphonates
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 em...
| Autores: | , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/222508 |
| Acesso em linha: | https://hdl.handle.net/2445/222508 |
| Access Level: | acceso abierto |
| Palavra-chave: | Lligands Malalties neurodegeneratives Envelliment Ligands Neurodegenerative Diseases Aging |
| Resumo: | 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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