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Recent progress in the drug discovery of non-peptidic BACE1 inhibitors

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Pages 391-416 | Published online: 03 Apr 2009

Keep up to date with the latest research on this topic with citation updates for this article.

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Prabu Manoharan, Kiranmai Chennoju & Nanda Ghoshal. (2018) Computational analysis of BACE1-ligand complex crystal structures and linear discriminant analysis for identification of BACE1 inhibitors with anti P-glycoprotein binding property. Journal of Biomolecular Structure and Dynamics 36:1, pages 262-276.
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Yoshio Hamada & Yoshiaki Kiso. (2013) Advances in the identification of β-secretase inhibitors. Expert Opinion on Drug Discovery 8:6, pages 709-731.
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Yoshio Hamada & Yoshiaki Kiso. (2012) The application of bioisosteres in drug design for novel drug discovery: focusing on acid protease inhibitors. Expert Opinion on Drug Discovery 7:10, pages 903-922.
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Jie Wu, Shanyun Gao, Guochao Liao, Hansen Lin & Aihua Nie. (2012) Diastereoselective Synthesis of N,N-Dibenzyl-Protected Aminoalkyl Hydroxyethylamines: Key Building Blocks for Hydroxyethylamine-Based BACE1 Inhibitor. Synthetic Communications 42:19, pages 2907-2916.
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Articles from other publishers (43)

Anuroopa G. Nadh, Amjesh Revikumar, P.R. Sudhakaran & Achuthsankar S. Nair. (2022) Identification of potential lead compounds against BACE1 through in-silico screening of phytochemicals of Medhya rasayana plants for Alzheimer's disease management. Computers in Biology and Medicine 145, pages 105422.
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Yoshio Hamada & Zyta M. Ziora. 2020. Peptide Synthesis. Peptide Synthesis 215 223 .
Yoshio Hamada & Yoshiaki Kiso. 2001. Kirk-Othmer Encyclopedia of Chemical Technology. Kirk-Othmer Encyclopedia of Chemical Technology 1 16 .
Yoshio Hamada. 2018. Pyridine. Pyridine.
Faten Atlam, Mohamed Awad & Rehab Salama. (2018) Factors Influencing the Potency of Alzheimer Inhibitors: Computational and Docking Studies. American Journal of Alzheimer's Disease & Other Dementias® 33:3, pages 166-175.
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Yoshio Hamada & Kenji Usui. 2018. Computational Modeling of Drugs Against Alzheimer’s Disease. Computational Modeling of Drugs Against Alzheimer’s Disease 207 228 .
Gang Yan, Lina Hao, Yan Niu, Wenjie Huang, Wei Wang, Fengrong Xu, Lei Liang, Chao Wang, Hongwei Jin & Ping Xu. (2017) 2-Substituted-thio- N -(4-substituted-thiazol/1 H -imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies. European Journal of Medicinal Chemistry 137, pages 462-475.
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Yoshio Hamada & Yoshiaki Kiso. 2017. Quantitative Structure-activity Relationship. Quantitative Structure-activity Relationship.
Yoshio Hamada & Yoshiaki Kiso. (2016) New directions for protease inhibitors directed drug discovery. Biopolymers 106:4, pages 563-579.
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Yoshio Hamada. (2016) Novel prodrugs with a spontaneous cleavable guanidine moiety. Bioorganic & Medicinal Chemistry Letters 26:7, pages 1685-1689.
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Yoshio Hamada. (2016) A novel N-terminal degradation reaction of peptides via N-amidination. Bioorganic & Medicinal Chemistry Letters 26:7, pages 1690-1695.
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Jia-Kuo Liu, Wei Gu, Xiao-Rui Cheng, Jun-Ping Cheng, Wen-Xia Zhou & Ai-Hua Nie. (2015) Design and synthesis of cyclic acylguanidines as BACE1 inhibitors. Chinese Chemical Letters 26:10, pages 1327-1330.
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Jian Liu, Wuyan Chen, Yechun Xu, Sumei Ren, Wei Zhang & Yingxia Li. (2015) Design, synthesis and biological evaluation of tasiamide B derivatives as BACE1 inhibitors. Bioorganic & Medicinal Chemistry 23:9, pages 1963-1974.
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Yoshio Hamada, Naoko Miyamoto & Yoshiaki Kiso. (2015) Novel β-amyloid aggregation inhibitors possessing a turn mimic. Bioorganic & Medicinal Chemistry Letters 25:7, pages 1572-1576.
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Yu Jin Hwang & Chaeuk Im. (2014) Docking and Quantitative Structure Activity Relationship studies of Acyl Guanidines as ?-Secretase (BACE1) Inhibitor. Bulletin of the Korean Chemical Society 35:7, pages 2065-2071.
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Peng Liu, Yan Niu, Chao Wang, Qi Sun, Yaya Zhai, Jiapei Yu, Jing Sun, Fengrong Xu, Gang Yan, Wenjie Huang, Lei Liang & Ping Xu. (2014) 4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: Synthesis, biological evaluation and docking studies. European Journal of Medicinal Chemistry 79, pages 413-421.
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Qiutian Jia, Yulin Deng & Hong Qing. (2014) Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β -Amyloid: Insights from Clinical Trials . BioMed Research International 2014, pages 1-22.
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Yoshio Hamada, Kenji Suzuki, Tomoya Nakanishi, Diganta Sarma, Hiroko Ohta, Ryoji Yamaguchi, Moe Yamasaki, Koushi Hidaka, Shoichi Ishiura & Yoshiaki Kiso. (2014) Structure–activity relationship study of BACE1 inhibitors possessing a chelidonic or 2,6-pyridinedicarboxylic scaffold at the P2 position. Bioorganic & Medicinal Chemistry Letters 24:2, pages 618-623.
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Maged M. Henary, Tyler L. Dost, Eric A. Owens & Surendra Reddy Punganuru. 2014. Drug Design and Discovery in Alzheimer's Disease. Drug Design and Discovery in Alzheimer's Disease 547 565 .
Kenji Suzuki, Yoshio Hamada, Jeffrey-Tri Nguyen & Yoshiaki Kiso. (2013) Novel BACE1 inhibitors with a non-acidic heterocycle at the P1′ position. Bioorganic & Medicinal Chemistry 21:21, pages 6665-6673.
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Yoshio Hamada. (2013) The Significance of Quantum Chemical Interactions for Medicinal Science and Design of β-Secretase Inhibitors創薬研究における量子化学的相互作用の重要性とβ-secretase阻害剤の設計. YAKUGAKU ZASSHI 133:10, pages 1113-1120.
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Daniel Oehlrich, Frederik J.R. Rombouts, Didier Berthelot, François P. Bischoff, Michel A.J. De Cleyn, Libuse Jaroskova, Gregor Macdonald, Marc Mercken, Michel Surkyn, Andrés A. Trabanco, Gary Tresadern, Sven Van Brandt, Adriana I. Velter, Tongfei Wu & Harrie J.M. Gijsen. (2013) Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 23:17, pages 4794-4800.
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Shuji Yonezawa, Hidekuni Yamakawa, Chie Muto, Motoko Hosono, Takahiko Yamamoto, Kazunari Hattori, Masahiro Sakagami, Hiroko Togame, Yoshikazu Tanaka, Toru Nakano, Hiroshi Takemoto, Mitsuhiro Arisawa & Satoshi Shuto. (2013) Conformational restriction approach to BACE1 inhibitors II: SAR study of the isocytosine derivatives fixed with a cis-cyclopropane ring. Bioorganic & Medicinal Chemistry Letters 23:10, pages 2912-2915.
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Ivan V. Efremov, Felix F. Vajdos, Kris A. Borzilleri, Steven Capetta, Hou Chen, Peter H. Dorff, Jason K. Dutra, Steven W. Goldstein, Mahmoud Mansour, Alexander McColl, Stephen Noell, Christine E. Oborski, Thomas N. O’Connell, Theresa J. O’Sullivan, Jayvardhan Pandit, Hong Wang, BinQing Wei & Jane M. Withka. (2012) Discovery and Optimization of a Novel Spiropyrrolidine Inhibitor of β-Secretase (BACE1) through Fragment-Based Drug Design. Journal of Medicinal Chemistry 55:21, pages 9069-9088.
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Christian Sund, Oscar Belda, Neera Borkakoti, Jimmy Lindberg, Dean Derbyshire, Lotta Vrang, Elizabeth Hamelink, Cathrine ?hgren, Esmeralda Woestenenk, Kristina Wikstr?m, Anders Eneroth, Erik Lindstr?m & Genadiy Kalayanov. (2012) Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates. Bioorganic & Medicinal Chemistry Letters 22:21, pages 6721-6727.
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Shuji Yonezawa, Takahiko Yamamoto, Hidekuni Yamakawa, Chie Muto, Motoko Hosono, Kazunari Hattori, Kenichi Higashino, Takashi Yutsudo, Hideo Iwamoto, Yutaka Kondo, Masahiro Sakagami, Hiroko Togame, Yoshikazu Tanaka, Toru Nakano, Hiroshi Takemoto, Mitsuhiro Arisawa & Satoshi Shuto. (2012) Conformational Restriction Approach to β-Secretase (BACE1) Inhibitors: Effect of a Cyclopropane Ring To Induce an Alternative Binding Mode. Journal of Medicinal Chemistry 55:20, pages 8838-8858.
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Yoshio Hamada, Tomoya Nakanishi, Kenji Suzuki, Ryoji Yamaguchi, Takashi Hamada, Koushi Hidaka, Shoichi Ishiura & Yoshiaki Kiso. (2012) Novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P2 position. Bioorganic & Medicinal Chemistry Letters 22:14, pages 4640-4644.
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Stephen A. Hitchcock. (2012) Structural Modifications that Alter the P-Glycoprotein Efflux Properties of Compounds. Journal of Medicinal Chemistry 55:11, pages 4877-4895.
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Holger Monenschein, Daniel B. Horne, Michael D. Bartberger, Stephen A. Hitchcock, Thomas T. Nguyen, Vinod F. Patel, Lewis D. Pennington & Wenge Zhong. (2012) Structure guided P1? modifications of HEA derived ?-secretase inhibitors for the treatment of Alzheimer?s disease. Bioorganic & Medicinal Chemistry Letters 22:11, pages 3607-3611.
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Heinrich Rueeger, Rainer Lueoend, Olivier Rogel, Jean-Michel Rondeau, Henrik Möbitz, Rainer Machauer, Laura Jacobson, Matthias Staufenbiel, Sandrine Desrayaud & Ulf Neumann. (2012) Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides. Journal of Medicinal Chemistry 55:7, pages 3364-3386.
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Yoshio Hamada, Shoichi Ishiura & Yoshiaki Kiso. (2011) BACE1 Inhibitor Peptides: Can an Infinitely Small k cat Value Turn the Substrate of an Enzyme into Its Inhibitor? . ACS Medicinal Chemistry Letters 3:3, pages 193-197.
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Britt-Marie Swahn, Jörg Holenz, Jacob Kihlström, Karin Kolmodin, Johan Lindström, Niklas Plobeck, Didier Rotticci, Fernando Sehgelmeble, Marie Sundström, Stefan von Berg, Johanna Fälting, Biljana Georgievska, Susanne Gustavsson, Jan Neelissen, Margareta Ek, Lise-Lotte Olsson & Stefan Berg. (2012) Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy. Bioorganic & Medicinal Chemistry Letters 22:5, pages 1854-1859.
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Yuan Cheng, Ted C. Judd, Michael D. Bartberger, James Brown, Kui Chen, Robert T. FremeauJr.Jr., Dean Hickman, Stephen A. Hitchcock, Brad Jordan, Vivian Li, Patricia Lopez, Steven W. Louie, Yi Luo, Klaus Michelsen, Thomas Nixey, Timothy S. Powers, Claire Rattan, E. Allen Sickmier, David J. St. JeanJr.Jr., Robert C. Wahl, Paul H. Wen & Stephen Wood. (2011) From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1). Journal of Medicinal Chemistry 54:16, pages 5836-5857.
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Heinrich Rueeger, Jean-Michel Rondeau, Clive McCarthy, Henrik Möbitz, Marina Tintelnot-Blomley, Ulf Neumann & Sandrine Desrayaud. (2011) Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors. Bioorganic & Medicinal Chemistry Letters 21:7, pages 1942-1947.
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Zyta Ziora, Mariusz Skwarczynski & Yoshiaki Kiso. 2011. Amino Acids, Peptides and Proteins in Organic Chemistry. Amino Acids, Peptides and Proteins in Organic Chemistry 189 245 .
Lawrence R. Marcin, Mendi A. Higgins, F. Christopher Zusi, Yunhui Zhang, Michael F. Dee, Michael F. Parker, Jodi K. Muckelbauer, Daniel M. Camac, Paul E. Morin, Vidhyashankar Ramamurthy, Andrew J. Tebben, Kimberley A. Lentz, James E. Grace, Jovita A. Marcinkeviciene, Lisa M. Kopcho, Catherine R. Burton, Donna M. Barten, Jeremy H. Toyn, Jere E. Meredith, Charles F. Albright, Joanne J. Bronson, John E. Macor & Lorin A. Thompson. (2011) Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1. Bioorganic & Medicinal Chemistry Letters 21:1, pages 537-541.
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Fredrik W?ngsell, Patrik Nordeman, Jonas S?vmarker, Rikard Emanuelsson, Katarina Jansson, Jimmy Lindberg, ?sa Rosenquist, Bertil Samuelsson & Mats Larhed. (2011) Investigation of ?-phenylnorstatine and ?-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors. Bioorganic & Medicinal Chemistry 19:1, pages 145-155.
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Anh P. Truong, Gergley Tóth, Gary D. Probst, Jennifer M. Sealy, Simeon Bowers, David W.G. Wone, Darren Dressen, Roy K. Hom, Andrei W. Konradi, Hing L. Sham, Jing Wu, Brian T. Peterson, Lany Ruslim, Michael P. Bova, Dora Kholodenko, Ruth N. Motter, Frédérique Bard, Pamela Santiago, Huifang Ni, David Chian, Ferdie Soriano, Tracy Cole, Elizabeth F. Brigham, Karina Wong, Wes Zmolek, Erich Goldbach, Bhushan Samant, Linda Chen, Hongbing Zhang, David F. Nakamura, Kevin P. Quinn, Ted A. Yednock & John-Michael Sauer. (2010) Design of an orally efficacious hydroxyethylamine (HEA) BACE-1 inhibitor in a preclinical animal model. Bioorganic & Medicinal Chemistry Letters 20:21, pages 6231-6236.
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Donald J. AbrahamAlbert J. Robichaud, Ji‐In Kim & J. Steven Jacobsen. 2003. Burger's Medicinal Chemistry and Drug Discovery. Burger's Medicinal Chemistry and Drug Discovery 329 404 .
Anh P. Truong, Gary D. Probst, Jose Aquino, Larry Fang, Louis Brogley, Jennifer M. Sealy, Roy K. Hom, John A. Tucker, Varghese John, Jay S. Tung, Michael A. Pleiss, Andrei W. Konradi, Hing L. Sham, Michael S. Dappen, Gergley Tóth, Nanhua Yao, Eric Brecht, Hu Pan, Dean R. Artis, Lany Ruslim, Michael P. Bova, Sukanto Sinha, Ted A. Yednock, Wes Zmolek, Kevin P. Quinn & John-Michael Sauer. (2010) Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: Structure–activity relationship of P2′ substituents. Bioorganic & Medicinal Chemistry Letters 20:16, pages 4789-4794.
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Taeko Kakizawa, Koushi Hidaka, Daisuke Hamada, Ryoji Yamaguchi, Tsuyoshi Uemura, Hitomi Kitamura, Harichandra D. Tagad, Takashi Hamada, Zyta Ziora, Yoshio Hamada, Tooru Kimura & Yoshiaki Kiso. (2010) Tetrapeptides, as small‐sized peptidic inhibitors; synthesis and their inhibitory activity against BACE1. Journal of Peptide Science 16:6, pages 257-262.
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Jared Cumming, Suresh Babu, Ying Huang, Carolyn Carrol, Xia Chen, Leonard Favreau, William Greenlee, Tao Guo, Matthew Kennedy, Reshma Kuvelkar, Thuy Le, Guoqing Li, Nansie McHugh, Peter Orth, Lynne Ozgur, Eric Parker, Kurt Saionz, Andrew Stamford, Corey Strickland, Dawit Tadesse, Johannes Voigt, Lili Zhang & Qi Zhang. (2010) Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization. Bioorganic & Medicinal Chemistry Letters 20:9, pages 2837-2842.
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Hemaka A. Rajapakse, Philippe G. Nantermet, Harold G. Selnick, James C. Barrow, Georgia B. McGaughey, Sanjeev Munshi, Stacey R. Lindsley, Mary Beth Young, Phung L. Ngo, M. Katherine Holloway, Ming-Tain Lai, Amy S. Espeseth, Xiao-Ping Shi, Dennis Colussi, Beth Pietrak, Ming-Chih Crouthamel, Katherine Tugusheva, Qian Huang, Min Xu, Adam J. Simon, Lawrence Kuo, Daria J. Hazuda, Samuel Graham & Joseph P. Vacca. (2010) SAR of tertiary carbinamine derived BACE1 inhibitors: Role of aspartate ligand amine pKa in enzyme inhibition. Bioorganic & Medicinal Chemistry Letters 20:6, pages 1885-1889.
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