One-Pot Cascade Synthesis of Pyrazole Based Isosteres of Valdecoxib by a [3+2] Cycloaddition Sequence and Evaluation of Their Cox Inhibitory Activity

Roscales García, Silvia; Kniess, Torsten; Bechmann, Nicole; Pietzsch, Jens

doi:10.3987/COM-19-14048

One-Pot Cascade Synthesis of Pyrazole Based Isosteres of Valdecoxib by a [3+2] Cycloaddition Sequence and Evaluation of Their Cox Inhibitory Activity

Roscales García, Silvia ¹
Kniess, Torsten ¹
Bechmann, Nicole
Pietzsch, Jens

1 Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden, Germany

Revista:

HETEROCYCLES

ISSN: 0385-5414

Año de publicación: 2019

Volumen: 98

Número: 3

Páginas: 416-428

Tipo: Artículo

DOI: 10.3987/COM-19-14048 GOOGLE SCHOLAR

Otras publicaciones en: HETEROCYCLES

Resumen

A series of 5-methyl-3,4-diaryl-substituted 1H-pyrazoles, N-isosteres of valdecoxib, was synthesized by a [3+2] cycloaddition/[1,5] sigmatropic rearrangement sequence starting from tosylhydrazine, aryl methyl ketones and terminal aryl alkynes bearing various substituents (H, Me, OMe, F, SO2Me, SO2NH2). New pyrazoles were prepared regioselectively in a one-pot process with moderate-good yields. All compounds were used in in vitro cyclooxygenase (COX) assays to determine inhibitory potency and selectivity to COX-1 and COX-2. In general, these new pyrazoles are characterized by selective COX-2 inhibition activity in a micromolar range.

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