Synthesis and Characterization of Novel Photoswitchable Tool Compounds to Enlighten β-Adrenoceptor Signalling
-adrenergic receptors ( -AR), a family of class A G Protein-Coupled Receptors, include three subtypes: 1-AR, 2-AR, and 3-AR. They are considered key targets in treating diseases such as heart failure and asthma with betablockers such as propranolol and agonists that are commonly structurall...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:dnet:digitalcsic_::c0e7effca2d4af0bd9d7043a4f6c6514 |
| Acceso en línea: | http://hdl.handle.net/10261/428415 |
| Access Level: | acceso abierto |
| Palabra clave: | Synthesis of drugs http://metadata.un.org/sdg/3 http://metadata.un.org/sdg/9 Ensure healthy lives and promote well-being for all at all ages Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation |
| Sumario: | -adrenergic receptors ( -AR), a family of class A G Protein-Coupled Receptors, include three subtypes: 1-AR, 2-AR, and 3-AR. They are considered key targets in treating diseases such as heart failure and asthma with betablockers such as propranolol and agonists that are commonly structurally based on endogenous ligands adrenaline and noradrenaline. To be able to study the complex nature of -AR signalling, developing new tool compounds with singular properties is considered appealing. For example, photopharmacology approaches allow for the spatial-temporal control of receptor activity. An established way to gain this spatial-temporal control is by the incorporation of a photoswitchable chemical moiety, (e.g. azobenzene), in the structure of ligands. Ideally, these photoswitchable ligands photo-isomerize between two isomers with different binding/functional properties toward the target receptor. In this work, three series of photoswitchable ligands for -ARs have been developed. In particular, the designed compounds include the common azobenzene moiety on either the ethanolamine N-tail of a conventional agnoists (series 1) or on the aromatic ring (series 2 and 3). The compounds of series 2 and 3 bear different N-tails in order to further elucidate the structure-activity relationship of photoagonists for -ARs and to potentially induce 1/ 2-AR selectivity. In total, one, six and six compounds of series 1, 2 and 3 respectively have been entirely synthesized and characterized and were shown to exhibit photoswitchable characteristics. |
|---|