Monoaryl- and bisaryldihydroxytropolones as potent inhibitors of inositol monophosphatase

Journal of Medicinal Chemistry
S R PiettreA J Ganzhorn

Abstract

The first successful preparation of mono- and disubstituted 3,7-dihydroxytropolone involves a four-step synthetic scheme. Thus, bromination of 3,7-dihydroxytropolone (8) followed by permethylation of the resultant products furnished gram quantities of intermediates 13-18. Single or double Suzuki coupling reactions between these permethylated monobromo- and dibromodihydroxytropolone derivatives and a variety of boronic acids delivered the expected products whose deprotection yielded the desired compounds 1a-u and 26a-n, usually in fair to good yields. Tropolones 1 and 26 were found to be potent inhibitors of inositol monophosphatase with IC50 values in the low-micromolar range. The results are discussed in the context of the recently described novel mode of inhibition of the enzyme by 3,7-dihydroxytropolones.

References

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Citations

Dec 5, 1998·Bioorganic & Medicinal Chemistry·A J GanzhornS R Piettre
Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Viktor A TafeenkoDmitrii A Khlevin
Nov 23, 2013·Future Medicinal Chemistry·Angela CoronaStuart F J Le Grice
Jan 28, 2006·Biochemical and Biophysical Research Communications·Anna M Boguszewska-ChachulskaMaria Bretner
Aug 5, 2014·MedChemComm·Christine MeckRyan P Murelli
Nov 4, 2017·Organic & Biomolecular Chemistry·D R HirschR P Murelli
Feb 9, 2017·Antimicrobial Agents and Chemotherapy·Maureen J DonlinRyan P Murelli
Jul 7, 2018·Beilstein Journal of Organic Chemistry·Arif DastanNurullah Saracoglu
Jul 23, 2014·Chemistry, an Asian Journal·Feiqing DingXue-Wei Liu
Aug 13, 1999·Journal of Enzyme Inhibition·C M Fauroux, S Freeman
Oct 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ellen BakStuart F J Le Grice
Jun 21, 2002·Organic Letters·Jack E BaldwinGareth J Pritchard
Apr 24, 2019·Journal of Natural Products·Ya-Jie SongWei-Dong Xie

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