Discovery of 6-(Fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for Quantification of Neurofibrillary Tangles (NFTs)

Journal of Medicinal Chemistry

Volumn 59, Issue 10, 2016, Pages 4778-4789

  Walji, Abbas M ^a   Hostetler, Eric D ^a   Selnick, Harold ^a   Zeng, Zhizhen ^a   Miller, Patricia ^a   Bennacef, Idriss ^a   Salinas, Cristian ^a   Connolly, Brett ^a   Gantert, Liza ^a   Holahan, Marie ^a   O'Malley, Stacey ^a   Purcell, Mona ^a   Riffel, Kerry ^a   Li, Jing ^a   Balsells, Jaume ^a   Obrien, Julie A ^a   Melquist, Stacey ^a   Soriano, Aileen ^a   Zhang, Xiaoping ^a   Ogawa, Aimie ^a   Xu, Serena ^a   Joshi, Elizabeth ^a   Della Rocca, Joseph ^a   Hess, Fred J ^a   Schachter, Joel ^a   Hesk, David ^a   Schenk, David ^a   Struyk, Arie ^a   Babaoglu, Kerim ^a   Lohith, Talakad G ^a   Wang, Yaode ^b   Yang, Kun ^b   Fu, Jianmin ^b   Evelhoch, Jeffrey L ^a   Coleman, Paul J ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b Pharmaron Beijing Co Ltd   (China)

Author keywords

[No Author keywords available]

Indexed keywords

FLUORINE; ISOQUINOLINE DERIVATIVE; MK-6240;

CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; HUMAN; METABOLISM; MOLECULAR IMAGING; NEUROFIBRILLARY TANGLE; PATHOLOGY; POSITRON EMISSION TOMOGRAPHY; SYNTHESIS;

DRUG DISCOVERY; FLUORINE RADIOISOTOPES; HUMANS; ISOQUINOLINES; MOLECULAR IMAGING; MOLECULAR STRUCTURE; NEUROFIBRILLARY TANGLES; POSITRON-EMISSION TOMOGRAPHY;

EID: 84971612059     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b00166     Document Type: Article

References (51)

1. Hampel, H.; Frank, R.; Broich, K.; Teipel, S. J.; Katz, R. G.; Hardy, J.; Herholz, K.; Bokde, A. L. W.; Jessen, F.; Hoessler, Y. C.; Sanhai, W. R.; Zetterberg, H.; Woodcock, J.; Blennow, K. Biomarkers for Alzheimer's Disease: Academic, Industry and Regulatory perspectives Nat. Rev. Drug Discovery 2010, 9, 560-574 10.1038/nrd3115
2. Jack, C. R.; Holtzman, D. M. Biomarker Modeling of Alzheimer's Disease Neuron 2013, 80, 1347-1358 10.1016/j.neuron.2013.12.003
3. Jagust, W. J.; Landau, S. M.; Koeppe, R. A.; Reiman, E. M.; Chen, K. W.; Mathis, C. A.; Price, J. C.; Foster, N. L.; Wang, A. Y. The Alzheimer's Disease Neuroimaging Initiative 2: PET core: 2015 Alzheimer's Dementia 2015, 11, 757-771 10.1016/j.jalz.2015.05.001
4. Frank, R.; Hargreaves, R. Clinical Biomarkers in Drug Discovery and Development Nat. Rev. Drug Discovery 2003, 2, 566-580 10.1038/nrd1130
5. Lista, S.; O'Bryant, S. E.; Blennow, K.; Dubois, B.; Hugon, J.; Zetterberg, H.; Hampel, H. Biomarkers in Sporadic and Familial Alzheimer's Disease J. Alzheimer's Dis. 2015, 47, 291-317 10.3233/JAD-143006
6. Rowe, C. C.; Ng, S.; Ackermann, U.; Gong, S. J.; Pike, K.; Savage, G.; Cowie, T. F.; Dickinson, K. L.; Maruff, P.; Darby, D.; Smith, C.; Woodward, M.; Merory, J.; Tochon-Danguy, H.; O'Keefe, G.; Klunk, W. E.; Mathis, C. A.; Price, J. C.; Masters, C. L.; Villemagne, V. L. Imaging β-Amyloid Burden in Aging and Dementia Neurology 2007, 68, 1718-1725 10.1212/01.wnl.0000261919.22630.ea
7. 18F]-DDNP with Hallmark Alzheimer's Disease Pathologies J. Neurochem. 2009, 109, 623-630 10.1111/j.1471-4159.2009.05996.x
8. Serdons, K.; Verduyckt, T.; Vanderghinste, D.; Cleynhens, J.; Borghgraef, P.; Vermaelen, P.; Terwinghe, C.; Van Leuven, F.; Van Laere, K.; Kung, H.; Bormans, G.; Verbruggen, A. Synthesis of F-18-Labelled 2-(4 ′-fluorophenyl)-1,3-benzothiazole and Evaluation as Amyloid Imaging Agent in Comparison with C-11 PIB Bioorg. Med. Chem. Lett. 2009, 19, 602-605 10.1016/j.bmcl.2008.12.069
9. Eckroat, T. J.; Mayhoub, A. S.; Garneau-Tsodikova, S. Amyloid-β Probes: Review of Structure-Activity and Brain-Kinetics Relationships Beilstein J. Org. Chem. 2013, 9, 1012-1044 10.3762/bjoc.9.116
10. Rowe, C. C.; Villemagne, V. L. Amyloid Imaging with PET in Early Alzheimer Disease Diagnosis Med. Clin. North Am. 2013, 97, 377-398 10.1016/j.mcna.2012.12.017
11. Kepe, V.; Moghbel, M. C.; Langstrom, B.; Zaidi, H.; Vinters, H. V.; Huang, S.-C.; Satyamurthy, N.; Doudet, D.; Mishani, E.; Cohen, R. M.; Hoilund-Carlsen, P. F.; Alavi, A.; Barrio, J. R. Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review J. Alzheimer's Dis. 2013, 36, 613-631 10.3233/JAD-130485
12. Landau, S. M.; Thomas, B. A.; Thurfjell, L.; Schmidt, M.; Margolin, R.; Mintun, M.; Pontecorvo, M.; Baker, S. L.; Jagust, W. J. Alzheimer's Dis Neuroimaging, I. Amyloid PET Imaging in Alzheimer's Disease: A Comparison of Three Radiotracers Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 1398-1407 10.1007/s00259-014-2753-3
13. Bolaender, A.; Kieser, D.; Voss, C.; Bauer, S.; Schoen, C.; Burgold, S.; Bittner, T.; Hoelzer, J.; Heyny-von Haussen, R.; Mall, G.; Goetschy, V.; Czech, C.; Knust, H.; Berger, R.; Herms, J.; Hilger, I.; Schmidtt, B. Bis(arylvinyl)pyrazines, -pyrimidines, and -pyridazines as Imaging Agents for Tau Fibrils and β-Amyloid Plaques in Alzheimer's Disease Models J. Med. Chem. 2012, 55, 9170-9180 10.1021/jm300653b
14. Harrison, S. T.; Mulhearn, J.; Wolkenberg, S. E.; Miller, P. J.; O'Malley, S. S.; Zeng, Z.; Williams, D. L., Jr.; Hostetler, E. D.; Sanabria-Bohorquez, S.; Gammage, L.; Fan, H.; Sur, C.; Culberson, J. C.; Hargreaves, R. J.; Cook, J. J.; Hartman, G. D.; Barrow, J. C. Synthesis and Evaluation of 5-fluoro-2-aryloxazolo 5,4-b pyridines as β-Amyloid PET Ligands and Identification of MK-3328 ACS Med. Chem. Lett. 2011, 2, 498-502 10.1021/ml200018n
15. Arriagada, P. V.; Growdon, J. H.; Hedleywhyte, E. T.; Hyman, B. T. Neurofibrillary Tangles but not Senile Plaques Parallel Duration and Severity of Alzheimer's-Disease Neurology 1992, 42, 631-639 10.1212/WNL.42.3.631
16. Andreadis, A.; Brown, W. M.; Kosik, K. S. Structure and Novel Exons of the Human-Tau Gene Biochemistry 1992, 31, 10626-10633 10.1021/bi00158a027
17. Buee, L.; Bussiere, T.; Buee-Scherrer, V.; Delacourte, A.; Hof, P. R. Tau Protein Isoforms, Phosphorylation and Role in Neurodegenerative Disorders Brain Res. Rev. 2000, 33, 95-130 10.1016/S0165-0173(00)00019-9
18. Buee, L.; Hamdane, M.; Delobel, P.; Bussiere, T.; Sergeant, N.; Delacourte, A. Role of Tau in Alzheimer's Disease and Other Tauopathies Mov. Disord. 2002, 17, 1407-1407
19. Maccioni, R. B.; Farias, G.; Morales, I.; Navarrete, L. The Revitalized Tau Hypothesis on Alzheimer's Disease Arch. Med. Res. 2010, 41, 226-231 10.1016/j.arcmed.2010.03.007
20. Spillantini, M. G.; Goedert, M. Tau Pathology and Neurodegeneration Lancet Neurol. 2013, 12, 609-622 10.1016/S1474-4422(13)70090-5
21. Alafuzoff, I.; Arzberger, T.; Al-Sarraj, S.; Bodi, I.; Bogdanovic, N.; Braak, H.; Bugiani, O.; Del-Tredici, K.; Ferrer, I.; Gelpi, E.; Giaccone, G.; Graeber, M. B.; Ince, P.; Kamphorst, W.; King, A.; Korkolopoulou, P.; Kovacs, G. G.; Larionov, S.; Meyronet, D.; Monoranu, C.; Parchi, P.; Patsouris, E.; Roggendorf, W.; Seilhean, D.; Tagliavini, F.; Stadelmann, C.; Streichenberger, N.; Thal, D. R.; Wharton, S. B.; Kretzschmar, H. Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the Brainnet Europe Consortium Brain Pathol. 2008, 18, 484-496 10.1111/j.1750-3639.2008.00147.x
22. Braak, H.; Braak, E. Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories Neurobiol. Aging 1997, 18, 351-357 10.1016/S0197-4580(97)00056-0
23. Delacourte, A.; David, J. P.; Sergeant, N.; Buee, L.; Wattez, A.; Vermersch, P.; Ghozali, F.; Fallet-Bianco, C.; Pasquier, F.; Lebert, F.; Petit, H.; Di Menza, C. The Biochemical Pathway of Neurofibrillary Degeneration in Aging and Alzheimer's Disease Neurology 1999, 52, 1158-1165 10.1212/WNL.52.6.1158
24. Villemagne, V. L.; Fodero-Tavoletti, M. T.; Masters, C. L.; Rowe, C. C. Tau Imaging: Early Progress and Future Directions Lancet Neurol. 2015, 14, 114-124 10.1016/S1474-4422(14)70252-2
25. Ariza, M.; Kolb, H. C.; Moechars, D.; Rombouts, F.; Andres, J. I. Tau Positron Emission Tomography (PET) Imaging: Past, Present, and Future J. Med. Chem. 2015, 58, 4365-4382 10.1021/jm5017544
26. Shah, M.; Catafau, A. M. Molecular Imaging Insights into Neurodegeneration: Focus on Tau PET Radiotracers J. Nucl. Med. 2014, 55, 871-874 10.2967/jnumed.113.136069
27. Mathis, C. A.; Klunk, W. E. Imaging Tau Deposits In Vivo: Progress in Viewing more of the Proteopathy Picture Neuron 2013, 79, 1035-1037 10.1016/j.neuron.2013.09.001
28. Villemagne, V. L.; Okamura, N. In Vivo Tau Imaging: Obstacles and Progress Alzheimer's Dementia 2014, 10, S254-S264 10.1016/j.jalz.2014.04.013
29. James, O. G.; Doraiswamy, P. M.; Borges-Neto, S. PET Imaging of Tau Pathology in Alzheimer's Disease and Tauopathies Front. Neurol. 2015, 6, 1-4 10.3389/fneur.2015.00038
30. Okamura, N.; Harada, R.; Furumoto, S.; Arai, H.; Yanai, K.; Kudo, Y. Tau PET Imaging in Alzheimer's Disease Curr. Neurol. Neurosci. Rep. 2014, 14, 1-7 10.1007/s11910-014-0500-6
31. 18F]-AV-1451) as a PET Biomarker for Neurodegeneration in Clinical Trials Neuropsychopharmacology 2014, 39, S207-S208
32. 18F]-T807) PET Tau Binding and Amyloid Burden in Cognitively Normal Subjects and Patients with Cognitive Impairments Suspected of Alzheimer's Disease. Abstract Number 245 J. Nucl. Med. 2015, 56, 245
33. 18F]-T807 J. Alzheimer's Dis. 2013, 34, 457-468 10.3233/JAD-122059
34. 18F]-T807, A Novel Tau Positron Emission Tomography Imaging Agent for Alzheimer's Disease Alzheimer's Dementia 2013, 9, 666-676 10.1016/j.jalz.2012.11.008
35. Chien, D. T.; Szardenings, A. K.; Bahri, S.; Walsh, J. C.; Mu, F.; Xia, C.; Shankle, W. R.; Lerner, A. J.; Su, M.-Y.; Elizarova, A.; Kolb, H. C. Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand F18-T808 J. Alzheimer's Dis. 2014, 38, 171-184 10.3233/JAD-130098
36. 18F]-THK-5117. Abstract Number 28 J. Nucl. Med. 2014, 55, 28
37. 18F]-THK-5117 PET for Assessing Neurofibrillary Pathology in Alzheimer's Disease Eur. J. Nucl. Med. Mol. Imaging 2015, 42, 1052-1061 10.1007/s00259-015-3035-4
38. 18F]-THK-5117 Positron Emission Tomography PLoS One 2015, 10, 1-9 10.1371/journal.pone.0140311
39. 18F]-THK-5351, A Novel PET Tracer for Imaging Tau Pathology in Alzheimer's Disease. Abstract Number 260 Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 260
40. Ito, H.; Shimada, H.; Ikoma, Y.; Shinotoh, H.; Kimura, Y.; Ichise, M.; Suhara, T.; Higuchi, M. Quantitative Analysis of Tau Pathology in Human Brain Using PET with C-11 PBB3 J. Nucl. Med. 2015, 56, 136
41. Wang, M.; Gao, M.; Xu, Z.; Zheng, Q.-H. Synthesis of a PET Tau Tracer C-11 PBB3 for Imaging of Alzheimer's Disease Bioorg. Med. Chem. Lett. 2015, 25, 4587-4592 10.1016/j.bmcl.2015.08.053
42. 18F]-T807 Tauopathy PET Imaging in Chronic Traumatic Encephalopathy F1000Research 2014, 3, 229 10.12688/f1000research.5372.1
43. 18F]-AV-1451 (T807) on postmortem brain tissue Ann. Neurol. 2015, 78, 787-800 10.1002/ana.24517
44. Vermeiren, C.; Mercier, J.; Viot, D.; Mairet-Coello, G.; Hannestad, J.; Courade, J.-P.; Citron, M.; Gillard, M. T807, A Reported Selective Tau Tracer, Binds with Nanomolar Affinity to Monoamine Oxidase A. Abstract Number 283 Alzheimer's Dementia 2015, 11, 283 10.1016/j.jalz.2015.07.381
45. Tarcsay, A.; Keseru, G. M. Contributions of Molecular Properties to Drug Promiscuity Miniperspective J. Med. Chem. 2013, 56, 1789-1795 10.1021/jm301514n
46. Hopkins, A. L.; Keserue, G. M.; Leeson, P. D.; Rees, D. C.; Reynolds, C. H. The Role of Ligand Efficiency Metrics in Drug Discovery Nat. Rev. Drug Discovery 2014, 13, 105-121 10.1038/nrd4163
47. Murray, C. W.; Erlanson, D. A.; Hopkins, A. L.; Keserue, G. M.; Leeson, P. D.; Rees, D. C.; Reynolds, C. H.; Richmond, N. J. Validity of Ligand Efficiency Metrics ACS Med. Chem. Lett. 2014, 5, 616-618 10.1021/ml500146d
48. Wager, T. T.; Hou, X.; Verhoest, P. R.; Villalobos, A. Moving Beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS-MPO) Approach to Enable Alignment of Druglike Properties ACS Chem. Neurosci. 2010, 1, 435-449 10.1021/cn100008c
49. 18F]-MK-3328: Evaluation of a Novel PET Tracer for Amyloid Plaque in Rhesus Monkey NeuroImage 2010, 52, S154 10.1016/j.neuroimage.2010.04.126
50. Walji, A. M.; Hostetler, E.; Greshock, T.; Li, J.; Moore, K. P.; Bennacef, I.; Mulhearn, J.; Selnick, H.; Wang, Y.; Yang, K.; Fu, J. Pyrrolo[2,3-c]pyridines as Imaging Agents for Neurofibrilary Tangles. WO2015191506A2, 2015.
51. Innis, R. B.; Cunningham, V. J.; Delforge, J.; Fujita, M.; Giedde, A.; Gunn, R. N.; Holden, J.; Houle, S.; Huang, S.-C.; Ichise, M.; Lida, H.; Ito, H.; Kimura, Y.; Koeppe, R. A.; Knudsen, G. M.; Knuuti, J.; Lammertsma, A. A.; Laruelle, M.; Logan, J.; Maguire, R. P.; Mintun, M. A.; Morris'o, E. D.; Parsey, R.; Price, J. C.; Slifstein, M.; Sossi, V.; Suhara, T.; Votaw, J. R.; Wong, D. F.; Carson, R. E. Consensus Nomenclature for In Vivo Imaging of Reversibly Binding Radioligands J. Cereb. Blood Flow Metab. 2007, 27, 1533-1539 10.1038/sj.jcbfm.9600493