title: Practical synthesis and cytotoxic evaluation of the pyrazino[1,2-b]-isoquinoline ring system.
abstract: A practical three-step protocol for the synthesis of pyrazino[1,2-b]isoquinolines is reported. This approach includes a one-pot parallel cyclization/cyclization parallel process followed by a non-common 6-endo Heck cyclization that transformed previously constructed Ugi adducts into diversely decorated tricyclic systems. Compounds bearing a t-butyl or 2,6-dimethylphenyl substituent showed significant cytotoxic activity. The most active analogue (6p) showed significant activity against HCT-15 and K562 (IC50 = 41.8 ± 3.3 and 57.7 ± 2.1 μM, respectively) with no cytotoxicity against human gingival fibroblasts.
authors.affiliation: Departamento de Química Orgánica, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, D.F. 04510, México. lmiranda@unam.mx.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hernández-Vázquez
authors.forename: Luis D
authors.initials: LD
authors.lastname: Miranda
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D020014:K562 Cells
chemical_list: D003603:Cytotoxins; D007546:Isoquinolines