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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Abstract

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
Volume26
Issue number8
Early online date10 Feb 2018
DOIs
Publication statusPublished - 1 May 2018

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Nitrites
Nitration
Thioamides
phthalimidine

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Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities. / Luo, Weiming ; Tweedie, David; Beedie, Shaunna-L.; Vargesson, Neil; Figg, William D; Greig, Nigel H. (Corresponding Author); Scerba, Michael T.

In: Bioorganic & Medicinal Chemistry, Vol. 26, No. 8, 01.05.2018, p. 1547-1559.

Research output: Contribution to journalArticle

Luo, Weiming ; Tweedie, David ; Beedie, Shaunna-L. ; Vargesson, Neil ; Figg, William D ; Greig, Nigel H. ; Scerba, Michael T. / Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities. In: Bioorganic & Medicinal Chemistry. 2018 ; Vol. 26, No. 8. pp. 1547-1559.
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abstract = "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.",
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AU - Figg, William D

AU - Greig, Nigel H.

AU - Scerba, Michael T.

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