Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists

This PhD thesis focuses on the development of novel, potent, and selective ligands for two therapeutically relevant GPCR targets: the dopamine receptor D2 and the cannabinoid receptor CB2. Different isocyanide-based multicomponent strategies were designed to generate focused small molecule collectio...

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Detalles Bibliográficos
Autor: Rodríguez García, Carlos
Tipo de recurso: tesis doctoral
Fecha de publicación:2024
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/34237
Acceso en línea:http://hdl.handle.net/10347/34237
Access Level:acceso abierto
Palabra clave:239001 Diseño. Síntesis y estudio nuevos fármacos
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spelling Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R AgonistsRodríguez García, Carlos239001 Diseño. Síntesis y estudio nuevos fármacosThis PhD thesis focuses on the development of novel, potent, and selective ligands for two therapeutically relevant GPCR targets: the dopamine receptor D2 and the cannabinoid receptor CB2. Different isocyanide-based multicomponent strategies were designed to generate focused small molecule collections that enabled the interrogation of the selected targets, the identification of new lead compounds and the evaluation of the most salient features of the SAR within these series. The first chapter deals with the optimization of novel Melanostatin-inspired allosteric modulators of the D2R. Chapter two documents a systematic MCR-assisted pharmacomodulation process that enabled the dissociation of the promiscuous cannabinomimetic profile of model designer drugs to identify potent, selective, and biased CB2R agonists. The research encompasses molecular design strategies, synthesis, biological evaluation, and structure-activity relationships. Preliminary evidence supporting the attractive antiproliferative activity of selected CB2R agonists in glioblastoma cell lines is also provided.Sotelo Pérez, EddyUniversidade de Santiago de Compostela. Escola de Doutoramento Internacional (EDIUS)20242024-01-0120242024-01-01doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10347/34237reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/342372026-06-15T12:47:27Z
dc.title.none.fl_str_mv Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
title Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
spellingShingle Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
Rodríguez García, Carlos
239001 Diseño. Síntesis y estudio nuevos fármacos
title_short Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
title_full Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
title_fullStr Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
title_full_unstemmed Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
title_sort Multicomponent Strategies for GPCR Targeting: Allosteric Modulation of Dopamine Receptor D2 and Development of Potent and Selective CB2R Agonists
dc.creator.none.fl_str_mv Rodríguez García, Carlos
author Rodríguez García, Carlos
author_facet Rodríguez García, Carlos
author_role author
dc.contributor.none.fl_str_mv Sotelo Pérez, Eddy
Universidade de Santiago de Compostela. Escola de Doutoramento Internacional (EDIUS)
dc.subject.none.fl_str_mv 239001 Diseño. Síntesis y estudio nuevos fármacos
topic 239001 Diseño. Síntesis y estudio nuevos fármacos
description This PhD thesis focuses on the development of novel, potent, and selective ligands for two therapeutically relevant GPCR targets: the dopamine receptor D2 and the cannabinoid receptor CB2. Different isocyanide-based multicomponent strategies were designed to generate focused small molecule collections that enabled the interrogation of the selected targets, the identification of new lead compounds and the evaluation of the most salient features of the SAR within these series. The first chapter deals with the optimization of novel Melanostatin-inspired allosteric modulators of the D2R. Chapter two documents a systematic MCR-assisted pharmacomodulation process that enabled the dissociation of the promiscuous cannabinomimetic profile of model designer drugs to identify potent, selective, and biased CB2R agonists. The research encompasses molecular design strategies, synthesis, biological evaluation, and structure-activity relationships. Preliminary evidence supporting the attractive antiproliferative activity of selected CB2R agonists in glioblastoma cell lines is also provided.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10347/34237
url http://hdl.handle.net/10347/34237
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
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repository.mail.fl_str_mv
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