Diversity-oriented synthesis and cytotoxic screening of fused dihydropyrazin-2(1H)-ones through a Ugi 4-CR/deprotection/Heck sequence
2020; Elsevier BV; Volume: 76; Issue: 36 Linguagem: Inglês
10.1016/j.tet.2020.131383
ISSN1464-5416
AutoresYoarhy A. Amador‐Sánchez, Eduardo Hernández‐Vázquez, Norberto González-Mojica, María Teresa Ramírez‐Apán, Luis D. Miranda,
Tópico(s)Synthesis and biological activity
ResumoAn expedited approach to the synthesis of fused-dihydropyrazin-2(1H)-ones from Ugi dimethylacetamide adducts is presented. The protocol relies on the formation of a C–N bond between the primary amide and the transitory oxocarbenium ion formed under acidic conditions, and then the construction of a fused-pyrazinone system after an intramolecular C(sp2)-C(sp2) Heck coupling. The methodology was able to generate 21 structurally diverse poly aza-heterocycles, a collection which was screened for its cytotoxicity in prostate, breast and lung cancer cell lines. The best activity was observed against the prostate cancer cell line PC-3 for two compounds with IC50 values of 23.6 and 20.9 μM, respectively.
Referência(s)