A novel class of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to investigate the affinity toward Hsp90 protein. The synthetic route was based on a 1,3-dipolar cycloaddition of nitriloxides, generated in situ from suitable benzaldoximes, with 2-bromocyclohex-2-enones or 3-bromo-5,6-dihydro-1H-pyridin-2-ones. Whereas all the compounds bearing a benzamide group on the bicyclic scaffold were devoid of activity, the derivatives carrying a resorcinol-like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme. A series of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to investigate affinity toward Hsp90 protein. Compounds carrying a resorcinol-like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme.
Synthesis of 5,6-dihydro-4H-benzo[d]isoxazol-7-one and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-one Derivatives as Potential Hsp90 Inhibitors / L. Musso, R. Cincinelli, G. Giannini, F. Manetti, S. Dallavalle. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0277. - 86:5(2015), pp. 1030-1035.
Titolo: | Synthesis of 5,6-dihydro-4H-benzo[d]isoxazol-7-one and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-one Derivatives as Potential Hsp90 Inhibitors |
Autori: | CINCINELLI, RAFFAELLA (Secondo) DALLAVALLE, SABRINA (Ultimo) |
Parole Chiave: | anticancer; docking calculations; Hsp90 inhibitors; isoxazoles; synthesis |
Settore Scientifico Disciplinare: | Settore CHIM/06 - Chimica Organica Settore CHIM/08 - Chimica Farmaceutica |
Data di pubblicazione: | 2015 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1111/cbdd.12570 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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