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Eur J Med Chem. 2014 Apr 9;76:53-60. doi: 10.1016/j.ejmech.2014.01.056. Epub 2014 Jan 30.

4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors.

Author information

1
Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
2
Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy. Electronic address: smd@unife.it.
3
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, Sezione di Farmacologia, Università di Palermo, Italy.
4
R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy. Electronic address: giuseppe.giannini@sigma-tau.it.
5
R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
6
Centro Interdipartimentale di Ricerca in Oncologia Clinica e Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Malattie Infettive, Università di Palermo, Palermo, Italy.

Abstract

Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]-pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6.

KEYWORDS:

4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines; Anti-cancer drugs; Heat shock protein 90

PMID:
24565573
DOI:
10.1016/j.ejmech.2014.01.056
[Indexed for MEDLINE]

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