Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities

Weiming Luo, David Tweedie, Shaunna-L. Beedie, Neil Vargesson, William D Figg, Nigel H. Greig (Corresponding Author), Michael T. Scerba

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A library of 15 novel and heretofore uncharacterized adamantyl and oradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF- α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF-α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF-α. Notable anti-angiogenesis activity was observed for 20, 21 and 22.
Original languageEnglish
Pages (from-to)1547-1559
Number of pages13
JournalBioorganic & Medicinal Chemistry
Issue number8
Early online date10 Feb 2018
Publication statusPublished - 1 May 2018


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