Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

Ghosh, Arun K.; Brindisi, Margherita; Yen, Yu-Chen; Cárdenas, Emilio L.; Ella-Menye, Jean-Rene; Kumaragurubaran, Nagaswamy; Huang, Xiangping; Tang, Jordan; Mesecar, Andrew D.

doi:10.1016/j.bmcl.2017.04.011

Title: Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

Authors:: Ghosh, Arun K.; Brindisi, Margherita; Yen, Yu-Chen; Cárdenas, Emilio L.; Ella-Menye, Jean-Rene; Kumaragurubaran, Nagaswamy; Huang, Xiangping; Tang, Jordan; Mesecar, Andrew D.

Publication Date:: Thu Jun 01 00:00:00 EDT 2017

Sponsoring Org.:: USDOE

OSTI Identifier:: 1416479

Grant/Contract Number:: AC02-06CH11357

Resource Type:: Publisher's Accepted Manuscript

Journal Name:: Bioorganic and Medicinal Chemistry Letters

Additional Journal Information:: Journal Name: Bioorganic and Medicinal Chemistry Letters Journal Volume: 27 Journal Issue: 11; Journal ID: ISSN 0960-894X

Publisher:: Elsevier

Country of Publication:: United Kingdom

Language:: English

Citation Formats


                    Ghosh, Arun K., Brindisi, Margherita, Yen, Yu-Chen, Cárdenas, Emilio L., Ella-Menye, Jean-Rene, Kumaragurubaran, Nagaswamy, Huang, Xiangping, Tang, Jordan, and Mesecar, Andrew D. Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands.  United Kingdom: N. p., 2017. 
Web.  doi:10.1016/j.bmcl.2017.04.011.

Copy to clipboard


                    Ghosh, Arun K., Brindisi, Margherita, Yen, Yu-Chen, Cárdenas, Emilio L., Ella-Menye, Jean-Rene, Kumaragurubaran, Nagaswamy, Huang, Xiangping, Tang, Jordan, & Mesecar, Andrew D. Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands.  United Kingdom.  https://doi.org/10.1016/j.bmcl.2017.04.011

Copy to clipboard


                    Ghosh, Arun K., Brindisi, Margherita, Yen, Yu-Chen, Cárdenas, Emilio L., Ella-Menye, Jean-Rene, Kumaragurubaran, Nagaswamy, Huang, Xiangping, Tang, Jordan, and Mesecar, Andrew D. Thu .  
"Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands".  United Kingdom.  https://doi.org/10.1016/j.bmcl.2017.04.011.

Copy to clipboard


                    
@article{osti_1416479,

  title        = {Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands},

  author       = {Ghosh, Arun K. and Brindisi, Margherita and Yen, Yu-Chen and Cárdenas, Emilio L. and Ella-Menye, Jean-Rene and Kumaragurubaran, Nagaswamy and Huang, Xiangping and Tang, Jordan and Mesecar, Andrew D.},

  abstractNote = {},

  doi          = {10.1016/j.bmcl.2017.04.011},

  journal      = {Bioorganic and Medicinal Chemistry Letters},

  number       = 11,

  volume       = 27,

  place        = {United Kingdom},

  year         = {Thu Jun 01 00:00:00 EDT 2017},

  month        = {Thu Jun 01 00:00:00 EDT 2017}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (Publisher)

Publisher's Version of Record
https://doi.org/10.1016/j.bmcl.2017.04.011

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 11 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS
journal, January 2016

Ghosh, Arun K.; Osswald, Heather L.; Prato, Gary
Journal of Medicinal Chemistry, Vol. 59, Issue 11
DOI: 10.1021/acs.jmedchem.5b01697

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease
journal, January 2014

Ghosh, Arun K.; Osswald, Heather L.
Chem. Soc. Rev., Vol. 43, Issue 19
DOI: 10.1039/C3CS60460H

A LZHEIMER'S D ISEASE : Molecular Understanding Predicts Amyloid-Based Therapeutics
journal, April 2003

Selkoe, Dennis J.; Schenk, Dale
Annual Review of Pharmacology and Toxicology, Vol. 43, Issue 1
DOI: 10.1146/annurev.pharmtox.43.100901.140248

Design, Synthesis, and X-ray Structure of Potent Memapsin 2 (β-Secretase) Inhibitors with Isophthalamide Derivatives as the P ₂ _- P ₃ -Ligands
journal, May 2007

Ghosh, Arun K.; Kumaragurubaran, Nagaswamy; Hong, Lin
Journal of Medicinal Chemistry, Vol. 50, Issue 10
DOI: 10.1021/jm061338s

Design, Synthesis, and Crystal Structure of Hydroxyethyl Secondary Amine-Based Peptidomimetic Inhibitors of Human β-Secretase ^†
journal, February 2007

Maillard, Michel C.; Hom, Roy K.; Benson, Timothy E.
Journal of Medicinal Chemistry, Vol. 50, Issue 4
DOI: 10.1021/jm061242y

Stereoselective Synthesis ofβ-Amino Alcohols from Optically Activeα-Amino Acids
journal, November 1987

Reetz, Manfred T.; Drewes, Mark W.; Schmitz, Alfred
Angewandte Chemie International Edition in English, Vol. 26, Issue 11
DOI: 10.1002/anie.198711411

Synthesis and Diastereoselective Reactions of N , N -Dibenzylamino Aldehydes and Related Compounds
journal, May 1999

Reetz, Manfred T.
Chemical Reviews, Vol. 99, Issue 5
DOI: 10.1021/cr980417b

Human aspartic protease memapsin 2 cleaves the beta -secretase site of beta -amyloid precursor protein
journal, February 2000

Lin, X.; Koelsch, G.; Wu, S.
Proceedings of the National Academy of Sciences, Vol. 97, Issue 4
DOI: 10.1073/pnas.97.4.1456

Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation
journal, February 2008

Ghosh, Arun K.; Kumaragurubaran, Nagaswamy; Hong, Lin
Bioorganic & Medicinal Chemistry Letters, Vol. 18, Issue 3
DOI: 10.1016/j.bmcl.2007.12.028

BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease
journal, December 2014

Vassar, Robert
Alzheimer's Research & Therapy, Vol. 6, Issue 9
DOI: 10.1186/s13195-014-0089-7

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors
journal, January 2008

Iserloh, U.; Wu, Y.; Cumming, J. N.
Bioorganic & Medicinal Chemistry Letters, Vol. 18, Issue 1
DOI: 10.1016/j.bmcl.2007.10.116

The global prevalence of dementia: A systematic review and metaanalysis
journal, January 2013

Prince, Martin; Bryce, Renata; Albanese, Emiliano
Alzheimer's & Dementia, Vol. 9, Issue 1
DOI: 10.1016/j.jalz.2012.11.007

BACE1 is the major β-secretase for generation of Aβ peptides by neurons
journal, March 2001

Cai, Huaibin; Wang, Yanshu; McCarthy, Diane
Nature Neuroscience, Vol. 4, Issue 3
DOI: 10.1038/85064

Proteolytic Activation of Recombinant Pro-memapsin 2 (Pro-β-secretase) Studied with New Fluorogenic Substrates
journal, September 2000

Ermolieff, Jacques; Loy, Jeffrey A.; Koelsch, Gerald
Biochemistry, Vol. 39, Issue 40
DOI: 10.1021/bi001494f

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
DOI: 10.1523/JNEUROSCI.3657-09.2009

β-Secretase inhibition for the treatment of Alzheimer's disease – promise and challenge
journal, February 2004

Citron, Martin
Trends in Pharmacological Sciences, Vol. 25, Issue 2
DOI: 10.1016/j.tips.2003.12.004

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
journal, July 2002

Hardy, J.
Science, Vol. 297, Issue 5580
DOI: 10.1126/science.1072994

A Review on the Use of Sodium Triacetoxyborohydride in the Reductive Amination of Ketones and Aldehydes
journal, September 2006

Abdel-Magid, Ahmed F.; Mehrman, Steven J.
Organic Process Research & Development, Vol. 10, Issue 5
DOI: 10.1021/op0601013

Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1)
journal, December 2004

Stachel, Shawn J.; Coburn, Craig A.; Steele, Thomas G.
Journal of Medicinal Chemistry, Vol. 47, Issue 26
DOI: 10.1021/jm049379g

Design, Synthesis and X-ray Structure of Protein−Ligand Complexes: Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors
journal, April 2006

Ghosh, Arun K.; Kumaragurubaran, Nagaswamy; Hong, Lin
Journal of the American Chemical Society, Vol. 128, Issue 16
DOI: 10.1021/ja058636j

Current concepts in Alzheimer’s Disease: molecules, models and translational perspectives
journal, January 2013

Rutten, Bart PF; Steinbusch, Harry WM
Molecular Neurodegeneration, Vol. 8, Issue 1
DOI: 10.1186/1750-1326-8-33

Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization
journal, May 2010

Cumming, Jared; Babu, Suresh; Huang, Ying
Bioorganic & Medicinal Chemistry Letters, Vol. 20, Issue 9
DOI: 10.1016/j.bmcl.2010.03.050

Synthesis of a 1-benzylpiperazin-2-one nitrone and its reaction with alkynes and alkenes
journal, October 1996

Bernotas, Ronald C.; Adams, Ginette
Tetrahedron Letters, Vol. 37, Issue 41
DOI: 10.1016/0040-4039(96)01640-1

Developing β-secretase inhibitors for treatment of Alzheimer’s disease: β-Secretase inhibitor drugs
journal, November 2011

Ghosh, Arun K.; Brindisi, Margherita; Tang, Jordan
Journal of Neurochemistry, Vol. 120
DOI: 10.1111/j.1471-4159.2011.07476.x

Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation
journal, March 2001

Luo, Yi; Bolon, Brad; Kahn, Steve
Nature Neuroscience, Vol. 4, Issue 3
DOI: 10.1038/85059

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors
journal, June 2008

Cumming, J. N.; Le, T. X.; Babu, S.
Bioorganic & Medicinal Chemistry Letters, Vol. 18, Issue 11
DOI: 10.1016/j.bmcl.2008.04.050

Non-Amide-Based Combinatorial Libraries Derived fromN-Boc-Iminodiacetic Acid: Solution-Phase Synthesis of Piperazinone Libraries with Activity Against LEF-1/β-Catenin-Mediated Transcription
journal, August 2000

Boger, Dale L.; Goldberg, Joel; Satoh, Shigeki
Helvetica Chimica Acta, Vol. 83, Issue 8
DOI: 10.1002/1522-2675(20000809)83:8<1825::AID-HLCA1825>3.0.CO;2-4

Characterization of lassa virus cell entry inhibitors: Determination of the active enantiomer by asymmetric synthesis
journal, July 2009

Whitby, Landon R.; Lee, Andrew M.; Kunz, Stefan
Bioorganic & Medicinal Chemistry Letters, Vol. 19, Issue 14
DOI: 10.1016/j.bmcl.2009.04.098

Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure
journal, September 2012

Ghosh, Arun K.; Venkateswara Rao, Kalapala; Yadav, Navnath D.
Journal of Medicinal Chemistry, Vol. 55, Issue 21
DOI: 10.1021/jm3008823

An effective treatment for Alzheimer's disease must consider both amyloid and tau
journal, February 2014

Lansdall, C. J.
Bioscience Horizons, Vol. 7, Issue 0
DOI: 10.1093/biohorizons/hzu002

BACE: Therapeutic target and potential biomarker for Alzheimer's disease
journal, December 2010

Evin, Geneviève; Barakat, Adel; Masters, Colin L.
The International Journal of Biochemistry & Cell Biology, Vol. 42, Issue 12
DOI: 10.1016/j.biocel.2010.08.017

Similar Records in DOE PAGES and OSTI.GOV collections:

Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1'-P2' ligands

Journal Article Ghosh, Arun K. ; Brindisi, Margherita ; Yen, Yu-Chen ; ... - Bioorganic and Medicinal Chemistry Letters
https://doi.org/10.1016/j.bmcl.2017.04.011
Design, Synthesis and X‐Ray Structural Studies of Potent HIV‐1 Protease Inhibitors Containing C‐4 Substituted Tricyclic Hexahydro‐Furofuran Derivatives as P2 Ligands

Journal Article Ghosh, Arun K. ; Kovela, Satish ; Sharma, Ashish ; ... - ChemMedChem

Abstract The design, synthesis, X‐ray structural, and biological evaluation of a series of highly potent HIV‐1 protease inhibitors are reported herein. These inhibitors incorporate novel cyclohexane‐fused tricyclic bis ‐tetrahydrofuran as P2 ligands in combination with a variety of P1 and P2′ ligands. The inhibitor with a difluoromethylphenyl P1 ligand and a cyclopropylaminobenzothiazole P2′ ligand exhibited the most potent antiviral activity. Also, it maintained potent antiviral activity against a panel of highly multidrug‐resistant HIV‐1 variants. The corresponding inhibitor with an enantiomeric ligand was significantly less potent in these antiviral assays. The new P2 ligands were synthesized in optically active form usingmore »« less
https://doi.org/10.1002/cmdc.202200058
Design, synthesis, biological evaluation and X-ray structural studies of HIV-1 protease inhibitors containing substituted fused-tetrahydropyranyl tetrahydrofuran as P2-ligands

Journal Article Ghosh, Arun K. ; Martyr, Cuthbert D. ; Kassekert, Luke A. ; ... - Organic and Biomolecular Chemistry

Design, synthesis, biological and X-ray crystallographic studies of a series of potent HIV-1 protease inhibitors are described. Various polar functionalities have been incorporated on the tetrahydropyranyl-tetrahydrofuran-derived P2 ligand to interact with the backbone atoms in the S2-subsite. Here, the majority of the inhibitors showed very potent enzyme inhibitory and antiviral activity. Two high-resolution X-ray structures of 30b- and 30j-bound HIV-1 protease provide insight into ligand-binding site interactions. In particular, the polar functionalities on the P2-ligand appear to form unique hydrogen bonds with Gly48 amide NH and amide carbonyl groups in the flap region.
Cited by 10
https://doi.org/10.1039/C5OB01930C

Full Text Available
Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

Journal Article Ghosh, Arun K. ; Fyvie, W. Sean ; Brindisi, Margherita ; ... - Bioorganic and Medicinal Chemistry Letters

Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (K_i = 13.2 nM, IC₅₀ = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. Lastly, these compounds showed excellent HIV-1 protease inhibitory (K_i = 62 pM and 14 pM, respectively) and antiviral activity (IC₅₀ = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.
Cited by 6
https://doi.org/10.1016/j.bmcl.2017.09.003

Full Text Available
Structure-Based Design of Highly Potent HIV-1 Protease Inhibitors Containing New Tricyclic Ring P2-Ligands: Design, Synthesis, Biological, and X-ray Structural Studies

Journal Article Ghosh, Arun K. ; Kovela, Satish ; Osswald, Heather L. ; ... - J. Med. Chem.
https://doi.org/10.1021/acs.jmedchem.0c00202

Similar Records

Title: Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

Citation Formats

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS journal, January 2016

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease journal, January 2014

A LZHEIMER'S D ISEASE : Molecular Understanding Predicts Amyloid-Based Therapeutics journal, April 2003

Design, Synthesis, and X-ray Structure of Potent Memapsin 2 (β-Secretase) Inhibitors with Isophthalamide Derivatives as the P 2 - P 3 -Ligands journal, May 2007

Design, Synthesis, and Crystal Structure of Hydroxyethyl Secondary Amine-Based Peptidomimetic Inhibitors of Human β-Secretase † journal, February 2007

Stereoselective Synthesis ofβ-Amino Alcohols from Optically Activeα-Amino Acids journal, November 1987

Synthesis and Diastereoselective Reactions of N , N -Dibenzylamino Aldehydes and Related Compounds journal, May 1999

Human aspartic protease memapsin 2 cleaves the beta -secretase site of beta -amyloid precursor protein journal, February 2000

Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation journal, February 2008

BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease journal, December 2014

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors journal, January 2008

The global prevalence of dementia: A systematic review and metaanalysis journal, January 2013

BACE1 is the major β-secretase for generation of Aβ peptides by neurons journal, March 2001

Proteolytic Activation of Recombinant Pro-memapsin 2 (Pro-β-secretase) Studied with New Fluorogenic Substrates journal, September 2000

The -Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential journal, October 2009

β-Secretase inhibition for the treatment of Alzheimer's disease – promise and challenge journal, February 2004

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics journal, July 2002

A Review on the Use of Sodium Triacetoxyborohydride in the Reductive Amination of Ketones and Aldehydes journal, September 2006

Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1) journal, December 2004

Design, Synthesis and X-ray Structure of Protein−Ligand Complexes: Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors journal, April 2006

Current concepts in Alzheimer’s Disease: molecules, models and translational perspectives journal, January 2013

Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization journal, May 2010

Synthesis of a 1-benzylpiperazin-2-one nitrone and its reaction with alkynes and alkenes journal, October 1996

Developing β-secretase inhibitors for treatment of Alzheimer’s disease: β-Secretase inhibitor drugs journal, November 2011

Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation journal, March 2001

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors journal, June 2008

Non-Amide-Based Combinatorial Libraries Derived fromN-Boc-Iminodiacetic Acid: Solution-Phase Synthesis of Piperazinone Libraries with Activity Against LEF-1/β-Catenin-Mediated Transcription journal, August 2000

Characterization of lassa virus cell entry inhibitors: Determination of the active enantiomer by asymmetric synthesis journal, July 2009

Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure journal, September 2012

An effective treatment for Alzheimer's disease must consider both amyloid and tau journal, February 2014

BACE: Therapeutic target and potential biomarker for Alzheimer's disease journal, December 2010

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS
journal, January 2016

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease
journal, January 2014

A LZHEIMER'S D ISEASE : Molecular Understanding Predicts Amyloid-Based Therapeutics
journal, April 2003

Design, Synthesis, and X-ray Structure of Potent Memapsin 2 (β-Secretase) Inhibitors with Isophthalamide Derivatives as the P ₂ _- P ₃ -Ligands
journal, May 2007

Design, Synthesis, and Crystal Structure of Hydroxyethyl Secondary Amine-Based Peptidomimetic Inhibitors of Human β-Secretase ^†
journal, February 2007

Stereoselective Synthesis ofβ-Amino Alcohols from Optically Activeα-Amino Acids
journal, November 1987

Synthesis and Diastereoselective Reactions of N , N -Dibenzylamino Aldehydes and Related Compounds
journal, May 1999

Human aspartic protease memapsin 2 cleaves the beta -secretase site of beta -amyloid precursor protein
journal, February 2000

Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation
journal, February 2008

BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease
journal, December 2014

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors
journal, January 2008

The global prevalence of dementia: A systematic review and metaanalysis
journal, January 2013

BACE1 is the major β-secretase for generation of Aβ peptides by neurons
journal, March 2001

Proteolytic Activation of Recombinant Pro-memapsin 2 (Pro-β-secretase) Studied with New Fluorogenic Substrates
journal, September 2000

The -Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential
journal, October 2009

β-Secretase inhibition for the treatment of Alzheimer's disease – promise and challenge
journal, February 2004

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
journal, July 2002

A Review on the Use of Sodium Triacetoxyborohydride in the Reductive Amination of Ketones and Aldehydes
journal, September 2006

Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1)
journal, December 2004

Design, Synthesis and X-ray Structure of Protein−Ligand Complexes: Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors
journal, April 2006

Current concepts in Alzheimer’s Disease: molecules, models and translational perspectives
journal, January 2013

Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization
journal, May 2010

Synthesis of a 1-benzylpiperazin-2-one nitrone and its reaction with alkynes and alkenes
journal, October 1996

Developing β-secretase inhibitors for treatment of Alzheimer’s disease: β-Secretase inhibitor drugs
journal, November 2011

Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation
journal, March 2001

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors
journal, June 2008

Non-Amide-Based Combinatorial Libraries Derived fromN-Boc-Iminodiacetic Acid: Solution-Phase Synthesis of Piperazinone Libraries with Activity Against LEF-1/β-Catenin-Mediated Transcription
journal, August 2000

Characterization of lassa virus cell entry inhibitors: Determination of the active enantiomer by asymmetric synthesis
journal, July 2009

Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure
journal, September 2012

An effective treatment for Alzheimer's disease must consider both amyloid and tau
journal, February 2014

BACE: Therapeutic target and potential biomarker for Alzheimer's disease
journal, December 2010