Síntesis diasteroselectiva de ((S)-2-((1-Etoxi-1-Oxo-4-Fenilbutan-2-Ilideno) Amino)-3-Hidroxipropanol) L-Prolina análogo del enalapril como posible inhibidor de la enzima convertidora de la angiotensina (IECA) para el tratamiento de la hipertensión

Abstract

High blood pressure has become a public health problem, the leading cause of death between the period 1998-2011, registering 628,630 deaths from cardiovascular disease, corresponding to 23.5% of all deaths in Colombia. It is a disease that is characterized by a significant increase in blood pressure in the arteries, where the population most vulnerable to this heart disease are people with on weight, diabetes type I and II and in adults older than 50 years (ECHEVERRI, 2016). Therefore, an approach to its treatment is based on new methods and drugs related to the origin of the disease being the latter the so-called antihypertensives (Baéz & Blanco, 2007).The antihypertensive drugs are part of pharmacological treatment for this heart disease, acting differently (as necessary treatment), such as beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors- II (ACE) inhibitors, angiotensin receptor blockers-II (BRA-II), alpha blockers, antihypertensive of central action and vessel dilators (Baéz & White, 2007). The most commercially used antihypertensive is the captopril known to inhibit the angiotensin-II-converting enzyme (IECA) which leads to a decrease in the levels of angiotensin II and aldosterone, achieving a resistance-reduction effect reduction of sodium and water retention, achieving a reducing action of blood pressure (General Health Council, 2011). The captopril was discovered by Brazilian researcher Mauricio Rocha e Silva in 1949 through tests with venom drops extracted from the tusks of the snake Bothrops Jararaca Jaracussa, which caused death from excessive blood pressure drop, found an analogous angiotensin I peptide (Serpa, 2010). Continuing with the studies, and wanting to improve the action of the drug are structural modifications made in the fundamental part where the proline is found in the captopril thus finding a drug more akin to the active site of the enzyme interacting by hydrogen bridges with the enalaprilate being this a prodrug, finally reaching the enalapril (Bautista, 2016) (González, 2017). Due to this modification, and the different types of IECA's already on the market, structural changes continued to be made to the drugs named above, using computational molecular chemistry as a fundamental tool and conducting molecular docking trials where other molecules with a greater affinity to the active site of the enzyme have been found, opening the way to the diastereoselective synthesis of new compounds that manage to inhibit the angiotensin-II converting enzyme (IECA) (González, 2017).