Publicación: Diuréticos tiazídicos: DHBTDs (1,1-Dióxido-3,4- dihidro-2H-1,2,4-benzotiadiazinas)
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2022-07-11
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Atribución-NoComercial-SinDerivadas 4.0 Internacional
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Universidad Nacional de Educación a Distancia (España). Facultad de Ciencias. Departamento de Química Orgánica y Bio-Orgánica
Resumen
La Química y en general la Ciencia tiene como objetivo satisfacer las necesidades de la sociedad. La hipertensión arterial (HTA) es una enfermedad que afecta, según la OMS, a más de 7,5 millones de personas, siendo esta una de las principales causas de muerte prematuras. Las 1,1-dioxido-1,2,4-benzotiadiazinas (DBTs), principalmente la hidroclorotiazida (HCTZ) es el antihipertensivo y diurético más utilizado desde 1957 para el tratamiento de la HTA. La característica más llamativa de estos compuestos es que muestran una amplia actividad biológica y medicinal que les permiten poder ser utilizados como agentes efectivos antitumorales, apertura de canales de potasio del ATP y como potenciador del receptor AMPA para tratar las etapas tempranas de la enfermedad del Alzheimer. Además, se han encontrado que posee actividad antiviral, en concreto contra el virus 6 del herpes humano (HHV-6), citomegalovirus humano (HCMV), el virus zoster de varicela (VZV) y es inhibidor de la polimerasa NS5B del virus de la hepatitis C. Por si fuera poco, se ha identificado como heterociclo inhibidor de la fosfodiesterasa 7 (PDE7) localizada en el cerebro, lo que permite la formación de nuevas neuronas. Así, considerando el gran valor farmacológico de estos heterociclos, la síntesis de estas moléculas ha tenido un gran interés desde de un punto de vista sintético y de la comunidad farmacéutica, por lo que se han descrito una serie de métodos de síntesis, incluyendo variantes enantioselectivas, muchos de los cuales, con desventajas en sus etapas sintéticas, como condiciones severas, limitaciones estructurales de los productos y la obtención de subproductos perjudiciales para el medioambiente. Aunque se han descrito posteriormente métodos de síntesis desde un punto de vista medioambiental y con una mayor economía atómica para obtener estos compuestos, en algunos casos sigue habiendo desconocimiento en el mecanismo de acción. Por ejemplo, el mecanismo de acción para la reducción de la presión arterial con las tiazidas diuréticas no está claro a pesar de investigaciones durante más de cinco décadas, por lo que estos compuestos siguen siendo objeto de estudios.
STRACT Chemistry and Science in general aims at meeting needs of society. Arterial hypertension (HTA) is a disease which affects, according to the WHO, over 7,5 million people, being the main cause of premature death. 1,2,4-benzothiadiazine 1,1-dioxide, namely hydrochlorothiazide (HCTZ) is the antihypertensive most widely prescribed therapeutic agents for treatment of HTA and diuretic since 1957. The feature most amazing of these compounds is that they show various useful biological and medicinal activity which allow them to be used as ATP-sensitive potassium channel openers and reduce the AMPA receptor desensitization, which is useful in the treatmen of early stages of Alzheimer disease. Furthermore, they have also been shown to possess antiviral activity, against humn herpes virus 6 (HHV-6), human citomegalovirus (H-CMV), Varicellarzoster virus (VZV) and hepatitis C virus NS5B polymerasa inhibitor. If that were not enough, it has been also reported as heterocyclic inhibitors of phosphodiesterasa 7 (PDE 7), which is in the brain and it allows to set up new neurons. Thus, considering the great pharmacological value of this heterocyclic scaffold, the synthesis of these molecules have received considerable interest from the viewpoint of synthetic and pharmaceutical community, due to what a number of efficient methods habe been described, including enantioselective variant, most of which with drawbacks of tedious synthetic steps, harsh conditions, structural limitation of products and harmful by-products. Although after it has been described methods of construction of heterocycles from the viewpoint of environmental issues and atom/step economy, sometimes there is still lack of awareness about the mechanism underlying chronic reduction of arterial pressure to thiazide diuretics and is unclear despite investigations over greater than five decades, and for this reason, the search continues in this kind of compounds.
STRACT Chemistry and Science in general aims at meeting needs of society. Arterial hypertension (HTA) is a disease which affects, according to the WHO, over 7,5 million people, being the main cause of premature death. 1,2,4-benzothiadiazine 1,1-dioxide, namely hydrochlorothiazide (HCTZ) is the antihypertensive most widely prescribed therapeutic agents for treatment of HTA and diuretic since 1957. The feature most amazing of these compounds is that they show various useful biological and medicinal activity which allow them to be used as ATP-sensitive potassium channel openers and reduce the AMPA receptor desensitization, which is useful in the treatmen of early stages of Alzheimer disease. Furthermore, they have also been shown to possess antiviral activity, against humn herpes virus 6 (HHV-6), human citomegalovirus (H-CMV), Varicellarzoster virus (VZV) and hepatitis C virus NS5B polymerasa inhibitor. If that were not enough, it has been also reported as heterocyclic inhibitors of phosphodiesterasa 7 (PDE 7), which is in the brain and it allows to set up new neurons. Thus, considering the great pharmacological value of this heterocyclic scaffold, the synthesis of these molecules have received considerable interest from the viewpoint of synthetic and pharmaceutical community, due to what a number of efficient methods habe been described, including enantioselective variant, most of which with drawbacks of tedious synthetic steps, harsh conditions, structural limitation of products and harmful by-products. Although after it has been described methods of construction of heterocycles from the viewpoint of environmental issues and atom/step economy, sometimes there is still lack of awareness about the mechanism underlying chronic reduction of arterial pressure to thiazide diuretics and is unclear despite investigations over greater than five decades, and for this reason, the search continues in this kind of compounds.
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Categorías UNESCO
Palabras clave
hipertensión arterial, hidroclorotiazida, antihipertensivo, agente diurético, arterial hypertension, hydrochlorothiazide, antihypertensive, diuretic agent
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Facultades y escuelas::Facultad de Ciencias
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