Synthesis and biological evaluation of pyridazinone analogues as potential cardiac positron emission tomography tracers

Journal of Medicinal Chemistry
Ajay PurohitDavid Casebier

Abstract

A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure-activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22-28) in Sprague-Dawley (SD) rats identified [18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.

References

Aug 1, 1992·Quarterly Reviews of Biophysics·J E Walker
Jul 1, 1992·Seminars in Nuclear Medicine·R A Koeppe, G D Hutchins
May 21, 1991·The American Journal of Cardiology·M Schwaiger, O Muzik
Feb 1, 1990·Circulation·D K Glover, R D Okada
May 1, 1994·Clinical Physiology·C A Nienaber
Feb 1, 1994·Biochemical Society Transactions·R M HollingworthJ L McLaughlin
Jun 19, 1998·Biochimica Et Biophysica Acta·M Degli Esposti
Jun 19, 1998·Biochimica Et Biophysica Acta·H Miyoshi
Jun 19, 1998·Biochimica Et Biophysica Acta·P Lümmen
Jan 5, 2002·Zeitschrift für Kardiologie·J vom Dahl
Nov 30, 2002·European Journal of Nuclear Medicine and Molecular Imaging·Akhil KapurS Richard Underwood
Mar 20, 2003·Molecular & Cellular Proteomics : MCP·Joe CarrollJohn E Walker
Dec 31, 2003·Bioorganic & Medicinal Chemistry Letters·Stephen D LindellRobert Klein
Jan 31, 2004·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·George A Beller, Steven R Bergmann
Jan 13, 2005·Seminars in Nuclear Medicine·Josef Machac
Feb 8, 2005·Radiologic Clinics of North America·Amol TakalkarLuis Araujo
Dec 3, 2005·Pharmazie in unserer Zeit·Hans Herzog, Frank Rösch
Dec 24, 2005·The International Journal of Cardiovascular Imaging·Riemer H J A SlartPieter L Jager
Nov 21, 2007·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Ming YuSimon P Robinson

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Citations

Mar 27, 2010·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Ming YuSimon P Robinson
Nov 22, 2013·European Journal of Nuclear Medicine and Molecular Imaging·Hideo TsukadaNorihiro Harada
Sep 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Manuela Kuchar, Constantin Mamat
Mar 30, 2010·Nuclear Medicine and Biology·Vijay GottumukkalaAlan B Packard
May 18, 2016·American Heart Journal·Lampros PapadimitriouJaved Butler
Aug 4, 2016·European Journal of Medicinal Chemistry·Wasim AkhtarM Mumtaz Alam
Sep 3, 2009·Physiological Genomics·Letizia PittoGiuseppe Rainaldi
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Norihiro HaradaHideo Tsukada
Feb 4, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tiantian MouXianzhong Zhang

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