Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3

Varlow, Cassis; Mossine, Andrew V.; Bernard-Gauthier, Vadim; Scott, Peter J. H.; Vasdev, Neil

doi:10.1016/j.jfluchem.2021.109760

Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3

Journal Article · Sat Feb 20 23:00:00 EST 2021 · Journal of Fluorine Chemistry

DOI:https://doi.org/10.1016/j.jfluchem.2021.109760· OSTI ID:1851649

Varlow, Cassis ^[1]; Mossine, Andrew V. ^[2]; Bernard-Gauthier, Vadim ^[3]; Scott, Peter J. H. ^[2]; ^[4]

Centre for Addiction and Mental Health, Toronto, ON, (Canada). Brain Health Imaging Centre. Azrieli Centre for Neuro-Radiochemistry; Univ. of Toronto, ON (Canada). Inst. of Medical Science; Univ. of Michigan, Ann Arbor, MI (United States)
Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Radiology
Centre for Addiction and Mental Health, Toronto, ON, (Canada). Brain Health Imaging Centre. Azrieli Centre for Neuro-Radiochemistry
Centre for Addiction and Mental Health, Toronto, ON, (Canada). Brain Health Imaging Centre. Azrieli Centre for Neuro-Radiochemistry; Univ. of Toronto, ON (Canada). Inst. of Medical Science

Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in oncology neurodegeneration, neuroinflammation and several mental health illnesses. As such, GSK-3 is a long-sought after target for positron emission tomography (PET) imaging and therapeutic intervention. Herein, we report on the development and radiofluorination of two oxazole-4- carboxamides, including one bearing a non-activated aromatic ring. Both compounds demonstrated excellent selectivity in a kinase screen and inhibit GSK-3 with high affinity. [¹⁸F]OCM-49 was synthesized from [¹⁸F]fluoride using a copper-mediated reaction of an aryl boronic acid precursor, while [¹⁸F]OCM-50 used a trimethylammonium triflate precursor, and both radiotracers were translated for preclinical PET imaging in rodents. Due to superior radiochemical yields and brain uptake (peak standardized uptake value of ~2.0), [¹⁸F]OCM-50 was further evaluated in non-human primate and also showed good brain uptake and rapid clearance. Finally, further studies to consider clinical translation of both radiotracers are underway.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH)

Grant/Contract Number:: SC0012484

OSTI ID:: 1851649

Alternate ID(s):: OSTI ID: 1781929

Journal Information:: Journal of Fluorine Chemistry, Journal Name: Journal of Fluorine Chemistry Journal Issue: C Vol. 245; ISSN 0022-1139

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (32)

Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D. Angewandte Chemie International Edition, Vol. 55, Issue 33 https://doi.org/10.1002/anie.201603797	journal	June 2016
Chemistry for Positron Emission Tomography: Recent Advances in ¹¹ C-, ¹⁸ F-, ¹³ N-, and ¹⁵ O-Labeling Reactions Deng, Xiaoyun; Rong, Jian; Wang, Lu Angewandte Chemie International Edition, Vol. 58, Issue 9 https://doi.org/10.1002/anie.201805501	journal	January 2019
Molecular cloning and expression of glycogen synthase kinase-3/factor A. Woodgett, J. R. The EMBO Journal, Vol. 9, Issue 8 https://doi.org/10.1002/j.1460-2075.1990.tb07419.x	journal	August 1990
Aryltrimethylammonium trifluoromethanesulfonates as precursors to aryl [18F]fluorides: Improved synthesis of [18F]GBR-13119 Haka, Michael S.; Kilbourn, Michael R.; Leonard Watkins, G. Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 27, Issue 7 https://doi.org/10.1002/jlcr.2580270711	journal	July 1989
Copper-mediated late-stage radiofluorination: five years of impact on preclinical and clinical PET imaging Wright, Jay S.; Kaur, Tanpreet; Preshlock, Sean Clinical and Translational Imaging, Vol. 8, Issue 3 https://doi.org/10.1007/s40336-020-00368-y	journal	May 2020
Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes Jope, Richard S. Trends in Pharmacological Sciences, Vol. 24, Issue 9 https://doi.org/10.1016/S0165-6147(03)00206-2	journal	September 2003
Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N′-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): A radiolabelled glycogen synthase kinase-3β specific inhibitor for PET studies Vasdev, Neil; Garcia, Armando; Stableford, Winston T. Bioorganic & Medicinal Chemistry Letters, Vol. 15, Issue 23 https://doi.org/10.1016/j.bmcl.2005.08.037	journal	December 2005
Radiosynthesis and preliminary PET evaluation of glycogen synthase kinase 3β (GSK-3β) inhibitors containing [11C]methylsulfanyl, [11C]methylsulfinyl or [11C]methylsulfonyl groups Kumata, Katsushi; Yui, Joji; Xie, Lin Bioorganic & Medicinal Chemistry Letters, Vol. 25, Issue 16 https://doi.org/10.1016/j.bmcl.2015.05.085	journal	August 2015
Radiosynthesis and evaluation of [11C]CMP, a high affinity GSK3 ligand Prabhakaran, Jaya; Sai, Kiran Kumar Solingapuram; Sattiraju, Anirudh Bioorganic & Medicinal Chemistry Letters, Vol. 29, Issue 6 https://doi.org/10.1016/j.bmcl.2019.01.033	journal	March 2019
Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β) Cole, Erin L.; Shao, Xia; Sherman, Phillip Nuclear Medicine and Biology, Vol. 41, Issue 6 https://doi.org/10.1016/j.nucmedbio.2014.03.025	journal	July 2014
The glamour and gloom of glycogen synthase kinase-3 Jope, Richard S.; Johnson, Gail V. W. Trends in Biochemical Sciences, Vol. 29, Issue 2 https://doi.org/10.1016/j.tibs.2003.12.004	journal	February 2004
Pharmacological inhibitors of glycogen synthase kinase 3 Meijer, L.; Flajolet, M.; Greengard, P. Trends in Pharmacological Sciences, Vol. 25, Issue 9 https://doi.org/10.1016/j.tips.2004.07.006	journal	September 2004
Synthesis of Diverse ¹¹ C-Labeled PET Radiotracers via Direct Incorporation of [ ¹¹ C]CO ₂ Mossine, Andrew V.; Brooks, Allen F.; Jackson, Isaac M. Bioconjugate Chemistry, Vol. 27, Issue 5 https://doi.org/10.1021/acs.bioconjchem.6b00163	journal	April 2016
Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery Bernard-Gauthier, Vadim; Mossine, Andrew V.; Knight, Ashley Journal of Medicinal Chemistry, Vol. 62, Issue 21 https://doi.org/10.1021/acs.jmedchem.9b01030	journal	September 2019
Synthesis of [ ¹⁸ F]Arenes via the Copper-Mediated [ ¹⁸ F]Fluorination of Boronic Acids Mossine, Andrew V.; Brooks, Allen F.; Makaravage, Katarina J. Organic Letters, Vol. 17, Issue 23 https://doi.org/10.1021/acs.orglett.5b02875	journal	November 2015
Radiosynthesis and in Vivo Evaluation of [ ¹¹ C]A1070722, a High Affinity GSK-3 PET Tracer in Primate Brain Prabhakaran, Jaya; Zanderigo, Francesca; Sai, Kiran Kumar Solingapuram ACS Chemical Neuroscience, Vol. 8, Issue 8 https://doi.org/10.1021/acschemneuro.6b00376	journal	May 2017
Synthesis and Initial in Vivo Studies with [ ¹¹ C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3 Li, Lei; Shao, Xia; Cole, Erin L. ACS Medicinal Chemistry Letters, Vol. 6, Issue 5 https://doi.org/10.1021/acsmedchemlett.5b00044	journal	March 2015
Development of [ ¹⁸ F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging Hu, Kongzhen; Patnaik, Debasis; Collier, Thomas Lee ACS Medicinal Chemistry Letters, Vol. 8, Issue 3 https://doi.org/10.1021/acsmedchemlett.6b00405	journal	February 2017
Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties Wager, Travis T.; Hou, Xinjun; Verhoest, Patrick R. ACS Chemical Neuroscience, Vol. 1, Issue 6 https://doi.org/10.1021/cn100008c	journal	March 2010
Toll-like receptor–mediated cytokine production is differentially regulated by glycogen synthase kinase 3 Martin, Michael; Rehani, Kunal; Jope, Richard S. Nature Immunology, Vol. 6, Issue 8 https://doi.org/10.1038/ni1221	journal	July 2005
GSK3 signalling in neural development Hur, Eun-Mi; Zhou, Feng-Quan Nature Reviews Neuroscience, Vol. 11, Issue 8 https://doi.org/10.1038/nrn2870	journal	August 2010
Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination Mossine, Andrew V.; Brooks, Allen F.; Ichiishi, Naoko Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-00110-1	journal	March 2017
A Design of Experiments (DoE) Approach Accelerates the Optimization of Copper-Mediated 18F-Fluorination Reactions of Arylstannanes Bowden, Gregory D.; Pichler, Bernd J.; Maurer, Andreas Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-47846-6	journal	August 2019
Late-stage [ ¹⁸ F]fluorination: new solutions to old problems Brooks, Allen F.; Topczewski, Joseph J.; Ichiishi, Naoko Chem. Sci., Vol. 5, Issue 12 https://doi.org/10.1039/C4SC02099E	journal	January 2014
Subject Review: Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation Arciniegas, MD, David; Adler, MD, Lawrence; Topkoff, Jeannie Brain Injury, Vol. 13, Issue 1 https://doi.org/10.1080/026990599121827	journal	January 1999
Inhibition of Glycogen Synthase Kinase-3: An Emerging Target in the Treatment of Traumatic Brain Injury Shim, Seong S.; Stutzmann, Grace E. Journal of Neurotrauma, Vol. 33, Issue 23 https://doi.org/10.1089/neu.2015.4177	journal	December 2016
The GSK3 hypothesis of Alzheimer’s disease: GSK3 and Alzheimer’s disease Hooper, Claudie; Killick, Richard; Lovestone, Simon Journal of Neurochemistry, Vol. 104, Issue 6 https://doi.org/10.1111/j.1471-4159.2007.05194.x	journal	December 2007
Lessons Learnt from Glycogen Synthase Kinase 3 Inhibitors Development for Alzheimer’s Disease Martinez, Ana; Perez, Daniel; Gil, Carmen Current Topics in Medicinal Chemistry, Vol. 13, Issue 15 https://doi.org/10.2174/15680266113139990138	journal	July 2013
Recent Advances in ¹⁸ F Radiochemistry: A Focus on B- ¹⁸ F, Si- ¹⁸ F, Al- ¹⁸ F, and C- ¹⁸ F Radiofluorination via Spirocyclic Iodonium Ylides Bernard-Gauthier, Vadim; Lepage, Mathieu L.; Waengler, Bjoern Journal of Nuclear Medicine, Vol. 59, Issue 4 https://doi.org/10.2967/jnumed.117.197095	journal	December 2017
GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS Eldar-Finkelman, Hagit; Martinez, Ana Frontiers in Molecular Neuroscience, Vol. 4 https://doi.org/10.3389/fnmol.2011.00032	journal	January 2011
Radiolabeled Small Molecule Protein Kinase Inhibitors for Imaging with PET or SPECT Hicks, Justin W.; VanBrocklin, Henry F.; Wilson, Alan A. Molecules, Vol. 15, Issue 11 https://doi.org/10.3390/molecules15118260	journal	November 2010
Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging Pandey, Mukesh K.; DeGrado, Timothy R. Theranostics, Vol. 6, Issue 4 https://doi.org/10.7150/thno.14334	journal	January 2016

Similar Records

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

Journal Article · Wed Jun 29 00:00:00 EDT 2016 · Angewandte Chemie (International Edition) · OSTI ID:1400568

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

Journal Article · Wed Jun 29 00:00:00 EDT 2016 · Angewandte Chemie · OSTI ID:1401450

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
60 APPLIED LIFE SCIENCES
Chemistry
GSK-3
PET imaging
copper-mediated radiofluorination
fluorine-18
glycogen synthase kinase 3
neuroimaging

Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3

Citation Formats

References (32)

Similar Records

Related Subjects