Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas

ilustraciones, diagramas

Autores:
Becerra Rivas, Christian Alonso
Tipo de recurso:
Doctoral thesis
Fecha de publicación:
2023
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/84352
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/84352
https://repositorio.unal.edu.co/
Palabra clave:
540 - Química y ciencias afines::547 - Química orgánica
Pirazoles
Pirimidinas
Tiazolidin-4-onas
GABA-A
Canal de sodio
Síntesis orgánica
Pyrazoles
Pyrimidines
Thiazolidin-4-ones
GABA-A
Sodium ion channel
Organic synthesis
heterocyclic compound
compuesto heterocíclico
Rights
openAccess
License
Atribución-NoComercial 4.0 Internacional
id UNACIONAL2_5f29fd16a3e054d5bc0037474fffd5bd
oai_identifier_str oai:repositorio.unal.edu.co:unal/84352
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
dc.title.translated.eng.fl_str_mv Rational design and synthesis of sulfur and nitrogen heterocycles with potential pharmacological activity on ion channels as regulators of nervous signals
title Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
spellingShingle Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
540 - Química y ciencias afines::547 - Química orgánica
Pirazoles
Pirimidinas
Tiazolidin-4-onas
GABA-A
Canal de sodio
Síntesis orgánica
Pyrazoles
Pyrimidines
Thiazolidin-4-ones
GABA-A
Sodium ion channel
Organic synthesis
heterocyclic compound
compuesto heterocíclico
title_short Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
title_full Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
title_fullStr Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
title_full_unstemmed Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
title_sort Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
dc.creator.fl_str_mv Becerra Rivas, Christian Alonso
dc.contributor.advisor.none.fl_str_mv Orozco Lopez, Fabian
dc.contributor.author.none.fl_str_mv Becerra Rivas, Christian Alonso
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)
dc.contributor.orcid.spa.fl_str_mv Christian Becerra [0000000296623813]
dc.contributor.cvlac.spa.fl_str_mv BECERRA RIVAS, CHRISTIAN ALONSO [0001535835]
dc.contributor.researchgate.spa.fl_str_mv Christian Alonso Becerra [Christian-Becerra]
dc.contributor.googlescholar.spa.fl_str_mv Christian Alonso Becerra Rivas [AJsN-F7-D4NJlHWfvCzFFoYK3QhTUbFz5pzpo46E8Bsiin981m6tOiF4UK2jLdZXDlh_SOl32nxOMRzvYaQkQpr3QZc9GaRN6A]
dc.subject.ddc.spa.fl_str_mv 540 - Química y ciencias afines::547 - Química orgánica
topic 540 - Química y ciencias afines::547 - Química orgánica
Pirazoles
Pirimidinas
Tiazolidin-4-onas
GABA-A
Canal de sodio
Síntesis orgánica
Pyrazoles
Pyrimidines
Thiazolidin-4-ones
GABA-A
Sodium ion channel
Organic synthesis
heterocyclic compound
compuesto heterocíclico
dc.subject.proposal.spa.fl_str_mv Pirazoles
Pirimidinas
Tiazolidin-4-onas
GABA-A
Canal de sodio
Síntesis orgánica
dc.subject.proposal.eng.fl_str_mv Pyrazoles
Pyrimidines
Thiazolidin-4-ones
GABA-A
Sodium ion channel
Organic synthesis
dc.subject.wikidata.eng.fl_str_mv heterocyclic compound
dc.subject.wikidata.spa.fl_str_mv compuesto heterocíclico
description ilustraciones, diagramas
publishDate 2023
dc.date.accessioned.none.fl_str_mv 2023-07-28T14:19:03Z
dc.date.available.none.fl_str_mv 2023-07-28T14:19:03Z
dc.date.issued.none.fl_str_mv 2023
dc.type.spa.fl_str_mv Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TD
format http://purl.org/coar/resource_type/c_db06
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/84352
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/84352
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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spelling Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Orozco Lopez, Fabiana68e5233b0410bc5b0dc8a0f900fff42Becerra Rivas, Christian Alonso07463f961c37a4d87104be6b63449dd0Grupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)Christian Becerra [0000000296623813]BECERRA RIVAS, CHRISTIAN ALONSO [0001535835]Christian Alonso Becerra [Christian-Becerra]Christian Alonso Becerra Rivas [AJsN-F7-D4NJlHWfvCzFFoYK3QhTUbFz5pzpo46E8Bsiin981m6tOiF4UK2jLdZXDlh_SOl32nxOMRzvYaQkQpr3QZc9GaRN6A]2023-07-28T14:19:03Z2023-07-28T14:19:03Z2023https://repositorio.unal.edu.co/handle/unal/84352Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasLos canales iónicos han despertado recientemente el interés de estudio desde la farmacología dada su potencial aplicación como dianas terapéuticas en el tratamiento de diversas patologías. En esta medida se planteó una biblioteca de compuestos de núcleo heterocíclico pirazólico, tiazolidinónico, tiazepínico y pirimidínico que pudieran interactuar con dianas moleculares de esta familia de proteínas; resultando de especial interés para este trabajo el receptor GABAA y el canal de sodio dependiente de voltaje NaV1.7. Dicha biblioteca se sometió a un proceso de cribado mediante docking molecular usando 3 programas (AutoDock4, AutoDock-VINA y DOCK6), determinación in silico de los descriptores moleculares de biodisponibilidad de Lipinski (ADME) y predicción de las propiedades toxicológicas, seleccionando los prototipos más promisorios y llevándolos a la fase de síntesis donde se estudiaron también las condiciones óptimas, así como sutilezas estructurales y de reactividad orientadas al mejoramiento de los procesos químicos que permitieron obtener con buenos rendimientos, 4 series de compuestos con un alto perfil promisorio en modulación de los canales iónicos diana para el tratamiento de enfermedades derivadas de una desregulación autonómica de las señales nerviosas. Además del nuevo conocimiento obtenido sobre los aspectos estructurales, cinéticos y termodinámicos pertinentes para la síntesis de las moléculas objetivo de interés para este estudio.Ion channels have recently aroused study interest from pharmacology, given their potential usage as therapeutic targets in the treatment of diverse pathologies. To this purpose, a library of compounds with heterocyclic nucleus such as pyrazole, thiazolidine, thiazepine and pyrimidine was proposed, so that they could interact with molecular targets of this family of proteins; resulting especially interesting for the purpose of this work, GABA-A receptor and voltage gated sodium channel NaV1.7. Mentioned library was subjected to a screening process by molecular docking using three programs (AutoDock4, AutoDock-VINA, and DOCK6), in silico calculus of Lipinski bioavailability descriptors (ADME) and prediction of toxicological properties, selecting the most promising prototypes and taking them to synthesis phase, where optimal conditions as well as structural and reactivity subtleties were studied, aiming for the improvement of the chemical processes that allowed to obtain with good yields, four series of compounds with high promising profile in modulation of the target ion channels for the treatment of diseases related from autonomic deregulation of nerve signals. Besides of new knowledge acquired about the structural, kinetic and thermodynamic aspects related with the synthesis of target molecules interesting for the purposes of this work.Ministerio de Ciencia Tecnología e Innovación (Minciencias)DoctoradoDoctor en Ciencias - QuímicaSíntesis Químicaxxviii, 369application/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en Ciencias - QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afines::547 - Química orgánicaPirazolesPirimidinasTiazolidin-4-onasGABA-ACanal de sodioSíntesis orgánicaPyrazolesPyrimidinesThiazolidin-4-onesGABA-ASodium ion channelOrganic synthesisheterocyclic compoundcompuesto heterocíclicoDiseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosasRational design and synthesis of sulfur and nitrogen heterocycles with potential pharmacological activity on ion channels as regulators of nervous signalsTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDM. 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Chem., vol. 43, no. 3, pp. 456–463, 2008.Y. Motoyama, K. Kamo, and H. Nagashima, “Catalysis in polysiloxane gels: Platinumcatalyzed hydrosilylation of polymethylhydrosiloxane leading to reusable catalysts for reduction of nitroarenes,” Org. Lett., vol. 11, no. 6, pp. 1345–1348, 2009.Síntesis multicomponente, cribado virtual y evaluación de la actividad tranquilizante de nuevos compuestos tiacepínicos, tiazolidínicos y quinolínicosMinisterio de Ciencia Tecnología e Innovación (Minciencias)EstudiantesInvestigadoresMaestrosMedios de comunicaciónProveedores de ayuda financiera para estudiantesORIGINAL1026276246 DQ2022-2.pdf1026276246 DQ2022-2.pdfTesis de Doctorado en Ciencias - Químicaapplication/pdf13364957https://repositorio.unal.edu.co/bitstream/unal/84352/2/1026276246%20DQ2022-2.pdf990570d9edab7f5f48f057e44b28ee18MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/84352/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53THUMBNAIL1026276246 DQ2022-2.pdf.jpg1026276246 DQ2022-2.pdf.jpgGenerated 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