title: Buchwald reaction as the key step for the synthesis of metabolically more stable analogs of amodiaquine.
abstract: Amodiaquine is one of the most active anti-malarial 4-aminoquinoline but its metabolization is believed to generate hepatotoxic derivatives. Previously, we described new analogs of amodiaquine and amopyroquine, in which hydroxyl group was replaced by various amino groups and identified highly potent compounds with lower toxicity. We describe here the synthesis of new analogs that have been modified on their 4'- and 5'-positions in order to reduce their metabolization. A new synthetic strategy was developed using Buchwald coupling reaction as the key step.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Le Fur
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hochart
authors.forename: Paul-Emmanuel
authors.initials: PE
authors.lastname: Larchanché
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
mesh_terms: D000655:Amodiaquine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D010165:Palladium / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D000655:Amodiaquine; D010165:Palladium