RESUMO
The first 1,3-dipolar cycloaddition of 2H-azirines with nitrones, a straightforward approach toward the regioselective synthesis of 1,2,4,5-tetrasubstituted imidazoles, is reported. This trifluoroacetic acid-catalyzed protocol tolerates a broad range of aliphatic and aromatic substrates, offering an efficient access to highly diverse, multisubstituted imidazoles in isolated yields up to 83% under mild conditions.
RESUMO
A regio- and diastereoselective 1,3-dipolar cycloaddition of 2 H-azirines with azomethine ylides generated in situ from isatins and α-amino acids has been elaborated, affording an unprecedented aziridine-fused spiro[imidazolidine-4,3'-oxindole] framework. This one-pot three-component reaction tolerates a wide range of substrates and enables the construction of highly diverse 1,3-diazaspiro[bicyclo[3.1.0]hexane]oxindoles in isolated yields up to 81% under mild conditions.
RESUMO
The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure-activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 µM).
Assuntos
Antineoplásicos/farmacologia , Imidazóis/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Pirazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Células HL-60 , Humanos , Imidazóis/síntese química , Imidazóis/química , Leucemia Promielocítica Aguda/patologia , Células MCF-7 , Camundongos , Pirazóis/síntese química , Pirazóis/química , Relação Estrutura-AtividadeRESUMO
A ZnCl2-catalyzed diastereoselective Joullié-Ugi three-component reaction from 2 H-azirines, isocyanides, and carboxylic acids was established. The protocol allows the preparation of highly and diversely functionalized N-acylaziridine-2-carboxamide derivatives in up to 82% isolated yields. Moreover, the applicability of N-acylaziridines is demonstrated through a variety of transformations.
RESUMO
A sequential one-pot approach towards N,N'-disubstituted guanidines from N-chlorophthalimide, isocyanides and amines is reported. This strategy provides straightforward and efficient access to diverse guanidines in yields up to 81% through previously unprecedented N-phthaloylguanidines. This protocol also features wide substrate scope and mild conditions.