title: New losartan-hydrocaffeic acid hybrids as antihypertensive-antioxidant dual drugs: Ester, amide and amine linkers.
abstract: We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Alcalá, Campus Universitario, 28871-Alcalá de Henares, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: García
authors.forename: Isabel
authors.initials: I
authors.lastname: Serrano
authors.forename: Patricia
authors.initials: P
authors.lastname: Sánchez-Alonso
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Puyol
authors.forename: Ramón
authors.initials: R
authors.lastname: Alajarín
authors.forename: Mercedes
authors.initials: M
authors.lastname: Griera
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Vaquero
authors.forename: Diego
authors.initials: D
authors.lastname: Rodríguez-Puyol
authors.forename: Julio
authors.initials: J
authors.lastname: Alvarez-Builla
authors.forename: María L
authors.initials: ML
authors.lastname: Díez-Marqués
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000588:Amines / Q000737:chemistry / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D002109:Caffeic Acids / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy; D019808:Losartan / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000577:Amides; D000588:Amines; D000959:Antihypertensive Agents; D000975:Antioxidants; D002109:Caffeic Acids; D004952:Esters; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019808:Losartan