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

作者：Baruchello Riccardo; Simoni Daniele^*; Marchetti Paolo; Rondanin Riccardo; Mangiola Stefania; Costantini Cristiana; Meli Maria; Giannini Giuseppe; Vesci Loredana; Carollo Valeria; Brunetti Tiziana; Battistuzzi Gianfranco; Tolomeo Manlio; Cabri Walter

来源：European Journal of Medicinal Chemistry, 2014, 76: 53-60.

DOI：10.1016/j.ejmech.2014.01.056

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

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.

• 出版日期2014-4-9