6533b858fe1ef96bd12b6d8a
RESEARCH PRODUCT
4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors.
Riccardo RondaninMaria MeliPaolo MarchettiGianfranco BattistuzziCristiana CostantiniDaniele SimoniValeria CarolloGiuseppe GianniniStefania MangiolaLoredana VesciRiccardo BaruchelloTiziana BrunettiWalter CabriManlio Tolomeosubject
Spectrometry Mass Electrospray IonizationMagnetic Resonance Spectroscopymedicine.drug_classStereochemistryPyridinesCarboxamideApoptosisResorcinolAnti-cancer drugschemistry.chemical_compoundResidue (chemistry)AmideDrug DiscoveryHeat shock protein 90 Anti-cancer drugs 4567-Tetrahydro-isoxazolo-[45-c]- pyridinesmedicineCytotoxic T cellHumansHeat shock protein 90HSP90 Heat-Shock ProteinsPharmacologyHydroxamic acidChemistryCell growthOrganic ChemistryGeneral MedicineNuclear magnetic resonance spectroscopy4 5 6 7-Tetrahydro-isoxazolo-[4 5-c]-pyridinesFlow CytometrySettore CHIM/08 - Chimica Farmaceuticahsp90Settore BIO/14 - Farmacologia4 5 6 7-Tetrahydro-isoxazolo-[4 5-c]-pyridines; Anti-cancer drugs; Heat shock protein 90;K562 CellsCell Divisiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 | European journal of medicinal chemistry |