(S)-4,5-dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid polyethers: a solution to nephrotoxicity.

Journal of Medicinal Chemistry
R J BergeronJames R Rocca

Abstract

Previous studies revealed that within a family of ligands the more lipophilic chelators have better iron-clearing efficiency. The larger the log P(app) value of the compound, the better the iron-clearing efficiency. What is also clear from the data is that although the relative effects of log P(app) changes are essentially the same through different families, there are differences in absolute value between families. However, there also exists a second, albeit somewhat more disturbing, relationship. In all sets of ligands, the most lipophilic chelator is always the most toxic. The current study focuses on designing ligands that balance the lipophilicity/toxicity problem while iron-clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH(3)O)-DADFT, 6] indicated that this methyl ether was a ligand with excellent iron-clearing efficiency in both rodents and primates; however, it was too toxic. On the basis of this finding, a less lipophilic, more water-soluble ligand than 6 was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE, 11], a polyether analogue, along wi...Continue Reading

References

Jul 1, 1991·Journal of Medicinal Chemistry·R J BergeronH H Peter
Jan 1, 1990·Annals of the New York Academy of Sciences·R J BergeronH B Jenny
Jul 1, 1989·Lancet·M G ZurloS Terzoli
Apr 1, 1989·Baillière's Clinical Haematology·M J Pippard
Feb 1, 1994·Free Radical Research·R T Dean, P Nicholson
Sep 1, 1994·The New England Journal of Medicine·G M BrittenhamJ W Harris
Jan 1, 1996·Acta Haematologica·N F Olivieri
Apr 12, 1996·Journal of Medicinal Chemistry·R J BergeronK Ratliff-Thompson
Jul 21, 1998·Annals of the New York Academy of Sciences·R J BergeronW R Weimar
Aug 13, 1998·The New England Journal of Medicine·N F OlivieriK A Fleming
Jan 15, 1999·Journal of Medicinal Chemistry·R J BergeronJ S McManis
Oct 16, 1999·The American Journal of the Medical Sciences·M E ConradE G Moore
Aug 3, 2000·The New England Journal of Medicine·E AngelucciG Lucarelli
Feb 24, 2001·Seminars in Hematology·E P Vichinsky
Feb 24, 2001·Seminars in Hematology·J B Porter
Feb 24, 2001·Molecular Aspects of Medicine·P T LieuY Yang
Mar 10, 2001·Clinics in Liver Disease·H L Bonkovsky, R W Lambrecht
May 1, 2001·The Journal of Laboratory and Clinical Medicine·D R Richardson
Jun 5, 2002·Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie·John P WojcikPaul C Adams
Apr 4, 2003·Journal of Medicinal Chemistry·Raymond J BergeronWilliam R Weimar
Jul 4, 2003·Chirality·Raymond J BergeronKhalil A Abboud
Feb 4, 2005·Journal of Medicinal Chemistry·Raymond J BergeronGary M Brittenham
Mar 2, 2005·Best Practice & Research. Clinical Haematology·M D Cappellini

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Citations

Nov 28, 2006·Journal of Medicinal Chemistry·Raymond J BergeronNeelam Bharti
Jun 15, 2007·Journal of Medicinal Chemistry·Raymond J BergeronJames R Rocca
Aug 15, 2012·Journal of Medicinal Chemistry·Raymond J BergeronJames S McManis
Jun 7, 2008·Journal of Medicinal Chemistry·Raymond J BergeronShailendra Singh
Sep 16, 2008·Journal of Medicinal Chemistry·Raymond J BergeronShailendra Singh
Nov 26, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Raymond J BergeronShailendra Singh
Apr 29, 2009·International Journal of Radiation Biology·Raymond J BergeronShailendra Singh
Sep 22, 2009·Drug Metabolism Reviews·Eugene D Weinberg, Jym Moon
Aug 2, 2015·Bioorganic & Medicinal Chemistry·Raymond J BergeronJan Wiegand
Sep 11, 2014·Journal of Medicinal Chemistry·Raymond J BergeronNeelam Bharti
Feb 18, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Robert C HiderTim Luker
Mar 7, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Tao ZhouRobert C Hider
Mar 5, 2019·Mini Reviews in Medicinal Chemistry·Mousumi ShyamVenkatesan Jayaprakash

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