3,4-Diarylisoxazoles-Analogues of Combretastatin A-4: Design, Synthesis, and Biological Evaluation In Vitro and In Vivo.

ABSTRACT: Focusing on the molecular docking results, a series of 3,4-diarylisoxazoles, analogues of Combretastatin A4, bearing various substituents at the fifth position of the isoxazole ring and pharmacophore groups bioisosteric to methoxy substituent at ring B, were synthesized in good yields and high regioselectivity. Depending on the substituent at C5, three approaches were chosen for the construction of isoxazole ring, including nitrosation of gem-dihalocyclopropanes, nitrile oxide synthesis, and difluoromethoxylation of isoxazolone to afford 5-haloisoxazoles, 5-unsubstituted isoxazoles, and 5-difluoromethoxyisoxazoles, respectively. Isoxazoles 43 and 45 showed selective cytotoxicity and antitubulin inhibition properties in vitro, with pharmacodynamic profiles closely relat

SUBMITTER: Karetnikov GL 

PROVIDER: S-EPMC10863432 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature