Synthesis of Diversely Substituted Diethyl (Pyrrolidin-2-Yl)Phosphonates
Imidazoline I receptors (I-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I-IR is limited. In this framework, we have reported several new structural families emb...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:312157 |
| Acceso en línea: | https://ddd.uab.cat/record/312157 https://dx.doi.org/urn:doi:10.3390/molecules30092078 |
| Access Level: | acceso abierto |
| Palabra clave: | α-aminophosphonate Pyrroline Phosphonic ester (Pyrrolidine-2-yl)phosphonate Phosphoproline Imidazoline I2 receptor ligand |
| Sumario: | Imidazoline I receptors (I-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I-IR is limited. In this framework, we have reported several new structural families embodying the iminophosphonate functional group that have an excellent affinity and selectivity for I-IR, and selected members have demonstrated relevant pharmacological properties in murine models of neurodegeneration and Alzheimer's disease. Starting with these iminophosphonates, we continued to exploit their high degree of functionalization through a short and efficient synthesis to access unprecedented 2,3-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 characterized by X-ray crystallographic analyses. Two selected compounds with structural features shared with the starting products were pharmacologically evaluated, allowing us to deduce the required key structural motifs for biologically active aminophosphonate derivatives. |
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