کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1394267 | 1501140 | 2014 | 8 صفحه PDF | دانلود رایگان |
• A series based on a tetrahydroisoxazolopyridine scaffold has been prepared.
• Some compounds bind to Hsp90 and have cytotoxic activity at micro/submicroM range.
• A resorcinol portion, bound as amide at N-5 demonstrated crucial for activity.
• C-3 carboxamide function is preferred to ester.
• A hydroxamic acid bound to C-3 carboxamide allows selective inhibition of HDAC6.
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.
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Journal: European Journal of Medicinal Chemistry - Volume 76, 9 April 2014, Pages 53–60