Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality
Abstract
A growing subset of $$β$$-secretase (BACE1) inhibitors for the treatment of Alzheimer’s disease (AD) utilizes an anilide chemotype that engages a key residue (Gly230) in the BACE1 binding site. Although the anilide moiety affords excellent potency, it simultaneously introduces a third hydrogen bond donor that limits brain availability and provides a potential metabolic site leading to the formation of an aniline, a structural motif of prospective safety concern. We report herein an alternative aminomethyl linker that delivers similar potency and improved brain penetration relative to the amide moiety. Optimization of this series identified analogues with an excellent balance of ADME properties and potency; however, potential drug–drug interactions (DDI) were predicted based on CYP 2D6 affinities. Generation and analysis of key BACE1 and CYP 2D6 crystal structures identified strategies to obviate the DDI liability, leading to compound 16, which exhibits robust in vivo efficacy as a BACE1 inhibitor.
- Authors:
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[1];
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- Pfizer Worldwide Research and Development, Cambridge, MA (United States)
- Pfizer Worldwide Research and Development, Groton, CT (United States)
- The Scripps Research Inst., La Jolla, CA (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Sponsoring Org.:
- Industrial Macromolecular Crystallography Association; USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Center for Research Resources, Biomedical Technology Program; National Institute of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1506536
- Grant/Contract Number:
- AC02-06CH11357; GM031001; AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Medicinal Chemistry
- Additional Journal Information:
- Journal Volume: 60; Journal Issue: 1; Journal ID: ISSN 0022-2623
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Substituents; Inhibitors; Inhibition; Amines; Selectivity
Citation Formats
Butler, Christopher R., Ogilvie, Kevin, Martinez-Alsina, Luis, Barreiro, Gabriela, Beck, Elizabeth M., Nolan, Charles E., Atchison, Kevin, Benvenuti, Eric, Buzon, Leanne, Doran, Shawn, Gonzales, Cathleen, Helal, Christopher J., Hou, Xinjun, Hsu, Mei-Hui, Johnson, Eric F., Lapham, Kimberly, Lanyon, Lorraine, Parris, Kevin, O’Neill, Brian T., Riddell, David, Robshaw, Ashley, Vajdos, Felix, and Brodney, Michael A. Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality. United States: N. p., 2016.
Web. doi:10.1021/acs.jmedchem.6b01451.
Butler, Christopher R., Ogilvie, Kevin, Martinez-Alsina, Luis, Barreiro, Gabriela, Beck, Elizabeth M., Nolan, Charles E., Atchison, Kevin, Benvenuti, Eric, Buzon, Leanne, Doran, Shawn, Gonzales, Cathleen, Helal, Christopher J., Hou, Xinjun, Hsu, Mei-Hui, Johnson, Eric F., Lapham, Kimberly, Lanyon, Lorraine, Parris, Kevin, O’Neill, Brian T., Riddell, David, Robshaw, Ashley, Vajdos, Felix, & Brodney, Michael A. Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality. United States. https://doi.org/10.1021/acs.jmedchem.6b01451
Butler, Christopher R., Ogilvie, Kevin, Martinez-Alsina, Luis, Barreiro, Gabriela, Beck, Elizabeth M., Nolan, Charles E., Atchison, Kevin, Benvenuti, Eric, Buzon, Leanne, Doran, Shawn, Gonzales, Cathleen, Helal, Christopher J., Hou, Xinjun, Hsu, Mei-Hui, Johnson, Eric F., Lapham, Kimberly, Lanyon, Lorraine, Parris, Kevin, O’Neill, Brian T., Riddell, David, Robshaw, Ashley, Vajdos, Felix, and Brodney, Michael A. Tue .
"Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality". United States. https://doi.org/10.1021/acs.jmedchem.6b01451. https://www.osti.gov/servlets/purl/1506536.
@article{osti_1506536,
title = {Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality},
author = {Butler, Christopher R. and Ogilvie, Kevin and Martinez-Alsina, Luis and Barreiro, Gabriela and Beck, Elizabeth M. and Nolan, Charles E. and Atchison, Kevin and Benvenuti, Eric and Buzon, Leanne and Doran, Shawn and Gonzales, Cathleen and Helal, Christopher J. and Hou, Xinjun and Hsu, Mei-Hui and Johnson, Eric F. and Lapham, Kimberly and Lanyon, Lorraine and Parris, Kevin and O’Neill, Brian T. and Riddell, David and Robshaw, Ashley and Vajdos, Felix and Brodney, Michael A.},
abstractNote = {A growing subset of $β$-secretase (BACE1) inhibitors for the treatment of Alzheimer’s disease (AD) utilizes an anilide chemotype that engages a key residue (Gly230) in the BACE1 binding site. Although the anilide moiety affords excellent potency, it simultaneously introduces a third hydrogen bond donor that limits brain availability and provides a potential metabolic site leading to the formation of an aniline, a structural motif of prospective safety concern. We report herein an alternative aminomethyl linker that delivers similar potency and improved brain penetration relative to the amide moiety. Optimization of this series identified analogues with an excellent balance of ADME properties and potency; however, potential drug–drug interactions (DDI) were predicted based on CYP 2D6 affinities. Generation and analysis of key BACE1 and CYP 2D6 crystal structures identified strategies to obviate the DDI liability, leading to compound 16, which exhibits robust in vivo efficacy as a BACE1 inhibitor.},
doi = {10.1021/acs.jmedchem.6b01451},
journal = {Journal of Medicinal Chemistry},
number = 1,
volume = 60,
place = {United States},
year = {Tue Dec 20 00:00:00 EST 2016},
month = {Tue Dec 20 00:00:00 EST 2016}
}
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Works referenced in this record:
Amyloid deposition as the central event in the aetiology of Alzheimer's disease
journal, January 1991
- Hardy, John; Allsop, David
- Trends in Pharmacological Sciences, Vol. 12
Twenty Years of the Alzheimer’s Disease Amyloid Hypothesis: A Genetic Perspective
journal, February 2005
- Tanzi, Rudolph E.; Bertram, Lars
- Cell, Vol. 120, Issue 4
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
journal, April 2010
- De Strooper, Bart
- Physiological Reviews, Vol. 90, Issue 2
The -Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential
journal, October 2009
- Vassar, R.; Kovacs, D. M.; Yan, R.
- Journal of Neuroscience, Vol. 29, Issue 41
BACE and γ-Secretase Characterization and Their Sorting as Therapeutic Targets to Reduce Amyloidogenesis
journal, September 2009
- Marks, Neville; Berg, Martin J.
- Neurochemical Research, Vol. 35, Issue 2
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
journal, July 2012
- Jonsson, Thorlakur; Atwal, Jasvinder K.; Steinberg, Stacy
- Nature, Vol. 488, Issue 7409
BACE1 as a Therapeutic Target in Alzheimer’s Disease: Rationale and Current Status
journal, July 2013
- Evin, Genevieve; Hince, Christopher
- Drugs & Aging, Vol. 30, Issue 10
hERG potassium channels and cardiac arrhythmia
journal, March 2006
- Sanguinetti, Michael C.; Tristani-Firouzi, Martin
- Nature, Vol. 440, Issue 7083
A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel
journal, April 1995
- Sanguinetti, Michael C.; Jiang, Changan; Curran, Mark E.
- Cell, Vol. 81, Issue 2
Drug-Induced Prolongation of the QT Interval
journal, March 2004
- Roden, Dan M.
- New England Journal of Medicine, Vol. 350, Issue 10
Robust Central Reduction of Amyloid- in Humans with an Orally Available, Non-Peptidic -Secretase Inhibitor
journal, November 2011
- May, P. C.; Dean, R. A.; Lowe, S. L.
- Journal of Neuroscience, Vol. 31, Issue 46
A quantitative assessment of hERG liability as a function of lipophilicity
journal, March 2007
- Waring, Michael J.; Johnstone, Craig
- Bioorganic & Medicinal Chemistry Letters, Vol. 17, Issue 6
Medicinal Chemistry of hERG Optimizations: Highlights and Hang-Ups
journal, August 2006
- Jamieson, Craig; Moir, Elizabeth M.; Rankovic, Zoran
- Journal of Medicinal Chemistry, Vol. 49, Issue 17
BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells
journal, June 2013
- Rochin, L.; Hurbain, I.; Serneels, L.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice
journal, February 2016
- Shimshek, Derya R.; Jacobson, Laura H.; Kolly, Carine
- Scientific Reports, Vol. 6, Issue 1
The evolution of amidine-based brain penetrant BACE1 inhibitors
journal, May 2014
- Oehlrich, Daniel; Prokopcova, Hana; Gijsen, Harrie J. M.
- Bioorganic & Medicinal Chemistry Letters, Vol. 24, Issue 9
BACE1 inhibitors: A head group scan on a series of amides
journal, July 2013
- Woltering, Thomas J.; Wostl, Wolfgang; Hilpert, Hans
- Bioorganic & Medicinal Chemistry Letters, Vol. 23, Issue 14
β-Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease
journal, May 2013
- Hilpert, Hans; Guba, Wolfgang; Woltering, Thomas J.
- Journal of Medicinal Chemistry, Vol. 56, Issue 10
1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads
journal, October 2015
- Rombouts, Frederik J. R.; Tresadern, Gary; Delgado, Oscar
- Journal of Medicinal Chemistry, Vol. 58, Issue 20
Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties
journal, March 2010
- Wager, Travis T.; Hou, Xinjun; Verhoest, Patrick R.
- ACS Chemical Neuroscience, Vol. 1, Issue 6
The Membrane-Bound Aspartyl Protease BACE1: Molecular and Functional Properties in Alzheimer’s Disease and Beyond
journal, January 2012
- Dislich, Bastian; Lichtenthaler, Stefan F.
- Frontiers in Physiology, Vol. 3
BACE1 as a Potential Biomarker for Alzheimer's Disease
journal, April 2011
- Decourt, Boris; Sabbagh, Marwan N.
- Journal of Alzheimer's Disease, Vol. 24, Issue s2
The Alzheimer's disease Beta-secretase enzyme, BACE1
journal, January 2007
- Cole, Sarah L.; Vassar, Robert
- Molecular Neurodegeneration, Vol. 2, Issue 1
Revisiting the peripheral sink hypothesis: inhibiting BACE1 activity in the periphery does not alter β-amyloid levels in the CNS
journal, September 2014
- Georgievska, Biljana; Gustavsson, Susanne; Lundkvist, Johan
- Journal of Neurochemistry, Vol. 132, Issue 4
Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain Aβ Reduction in Rodents
journal, January 2016
- Wu, Yong-Jin; Guernon, Jason; Yang, Fukang
- ACS Medicinal Chemistry Letters, Vol. 7, Issue 3
Structural Alert/Reactive Metabolite Concept as Applied in Medicinal Chemistry to Mitigate the Risk of Idiosyncratic Drug Toxicity: A Perspective Based on the Critical Examination of Trends in the Top 200 Drugs Marketed in the United States
journal, September 2011
- Stepan, Antonia F.; Walker, Daniel P.; Bauman, Jonathan
- Chemical Research in Toxicology, Vol. 24, Issue 9
Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design
journal, February 2015
- Butler, Christopher R.; Brodney, Michael A.; Beck, Elizabeth M.
- Journal of Medicinal Chemistry, Vol. 58, Issue 6
Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.
journal, July 2008
- Shalaeva, Marina; Kenseth, Jeremy; Lombardo, Franco
- Journal of Pharmaceutical Sciences, Vol. 97, Issue 7
Cerebrospinal Fluid Amyloid-β (Aβ) as an Effect Biomarker for Brain Aβ Lowering Verified by Quantitative Preclinical Analyses
journal, May 2012
- Lu, Yasong; Riddell, David; Hajos-Korcsok, Eva
- Journal of Pharmacology and Experimental Therapeutics, Vol. 342, Issue 2
Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and Inhibitors
journal, January 1997
- Rendic, Slobodan; Carlo, Frederick J. Di
- Drug Metabolism Reviews, Vol. 29, Issue 1-2
Pharmacogenomics of CYP2D6: Molecular Genetics, Interethnic Differences and Clinical Importance
journal, January 2012
- Teh, Lay Kek; Bertilsson, Leif
- Drug Metabolism and Pharmacokinetics, Vol. 27, Issue 1
Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs: Molecular genetics of CYP2D6
journal, January 2002
- Bertilsson, Leif; Dahl, Marja-Liisa; Dalén, Per
- British Journal of Clinical Pharmacology, Vol. 53, Issue 2
Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug–Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors
journal, March 2015
- Brodney, Michael A.; Beck, Elizabeth M.; Butler, Christopher R.
- Journal of Medicinal Chemistry, Vol. 58, Issue 7
Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery
journal, January 2002
- Cory Kalvass, J.; Maurer, Tristan S.
- Biopharmaceutics & Drug Disposition, Vol. 23, Issue 8
Characterization of Potassium Channel Modulators with QPatch ™ Automated Patch-Clamp Technology: System Characteristics and Performance
journal, October 2003
- Kutchinsky, Jonatan; Friis, Søren; Asmild, Margit
- ASSAY and Drug Development Technologies, Vol. 1, Issue 5
A novel approach to identifying β-secretase inhibitors: Bis-statine peptide mimetics discovered using structure and spot synthesis
journal, July 2006
- Bridges, Kristie Grove; Chopra, Rajiv; Lin, Laura
- Peptides, Vol. 27, Issue 7
Data processing and analysis with the autoPROC toolbox
journal, March 2011
- Vonrhein, Clemens; Flensburg, Claus; Keller, Peter
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
On the treatment of negative intensity observations
journal, July 1978
- French, S.; Wilson, K.
- Acta Crystallographica Section A, Vol. 34, Issue 4
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997
- Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States
journal, September 2011
- Stepan, Antonia F.; Walker, Daniel P.; Bauman, Jonathan
- Chemical Research in Toxicology, Vol. 24, Issue 9, 1345-1410
Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties
journal, June 2010
- Wager, Travis T.; Hou, Xinjun; Verhoest, Patrick R.
- ACS Chemical Neuroscience, Vol. 1, Issue 6, 435-449
BACE1 as a Therapeutic Target in Alzheimer’s Disease: Rationale and Current Status
journal, July 2013
- Evin, Genevieve; Hince, Christopher
- Drugs & Aging, Vol. 30, Issue 10
The evolution of amidine-based brain penetrant BACE1 inhibitors
journal, May 2014
- Oehlrich, Daniel; Prokopcova, Hana; Gijsen, Harrie J. M.
- Bioorganic & Medicinal Chemistry Letters, Vol. 24, Issue 9
Twenty Years of the Alzheimer’s Disease Amyloid Hypothesis: A Genetic Perspective
journal, February 2005
- Tanzi, Rudolph E.; Bertram, Lars
- Cell, Vol. 120, Issue 4
A novel approach to identifying β-secretase inhibitors: Bis-statine peptide mimetics discovered using structure and spot synthesis
journal, July 2006
- Bridges, Kristie Grove; Chopra, Rajiv; Lin, Laura
- Peptides, Vol. 27, Issue 7
1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads
journal, October 2015
- Rombouts, Frederik J. R.; Tresadern, Gary; Delgado, Oscar
- Journal of Medicinal Chemistry, Vol. 58, Issue 20
Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain Aβ Reduction in Rodents
journal, January 2016
- Wu, Yong-Jin; Guernon, Jason; Yang, Fukang
- ACS Medicinal Chemistry Letters, Vol. 7, Issue 3
Medicinal Chemistry of hERG Optimizations: Highlights and Hang-Ups
journal, August 2006
- Jamieson, Craig; Moir, Elizabeth M.; Rankovic, Zoran
- Journal of Medicinal Chemistry, Vol. 49, Issue 17
β-Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease
journal, May 2013
- Hilpert, Hans; Guba, Wolfgang; Woltering, Thomas J.
- Journal of Medicinal Chemistry, Vol. 56, Issue 10
Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design
journal, February 2015
- Butler, Christopher R.; Brodney, Michael A.; Beck, Elizabeth M.
- Journal of Medicinal Chemistry, Vol. 58, Issue 6
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
journal, July 2012
- Jonsson, Thorlakur; Atwal, Jasvinder K.; Steinberg, Stacy
- Nature, Vol. 488, Issue 7409
Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice
journal, February 2016
- Shimshek, Derya R.; Jacobson, Laura H.; Kolly, Carine
- Scientific Reports, Vol. 6, Issue 1
Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs: Molecular genetics of CYP2D6
journal, January 2002
- Bertilsson, Leif; Dahl, Marja-Liisa; Dalén, Per
- British Journal of Clinical Pharmacology, Vol. 53, Issue 2
BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells
journal, June 2013
- Rochin, L.; Hurbain, I.; Serneels, L.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
Characterization of Potassium Channel Modulators with QPatch ™ Automated Patch-Clamp Technology: System Characteristics and Performance
journal, October 2003
- Kutchinsky, Jonatan; Friis, Søren; Asmild, Margit
- ASSAY and Drug Development Technologies, Vol. 1, Issue 5
Revisiting the peripheral sink hypothesis: inhibiting BACE1 activity in the periphery does not alter β-amyloid levels in the CNS
journal, September 2014
- Georgievska, Biljana; Gustavsson, Susanne; Lundkvist, Johan
- Journal of Neurochemistry, Vol. 132, Issue 4
Cerebrospinal Fluid Amyloid-β (Aβ) as an Effect Biomarker for Brain Aβ Lowering Verified by Quantitative Preclinical Analyses
journal, May 2012
- Lu, Yasong; Riddell, David; Hajos-Korcsok, Eva
- Journal of Pharmacology and Experimental Therapeutics, Vol. 342, Issue 2
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
journal, April 2010
- De Strooper, Bart
- Physiological Reviews, Vol. 90, Issue 2
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
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- Williams, Ibidapo S.; Gatchie, Linda; Bharate, Sandip B.
- ACS Omega, Vol. 3, Issue 8
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