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Novel γ-secretase modulators: a review of patents from 2008 to 2010

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Pages 205-226 | Published online: 14 Jan 2011

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Martin Pettersson, Antonia F Stepan, Gregory W Kauffman & Douglas S Johnson. (2013) Novel γ-secretase modulators for the treatment of Alzheimer's disease: a review focusing on patents from 2010 to 2012. Expert Opinion on Therapeutic Patents 23:10, pages 1349-1366.
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Petra Dunkel, Christina LL Chai, Beáta Sperlágh, Paul B Huleatt & Péter Mátyus. (2012) Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Expert Opinion on Investigational Drugs 21:9, pages 1267-1308.
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Jiachen Wen, Dan Liu & Linxiang Zhao. (2022) Small molecules targeting γ-secretase and their potential biological applications. European Journal of Medicinal Chemistry 232, pages 114169.
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Shekar Mekala, Grady Nelson & Yue-Ming Li. (2020) Recent developments of small molecule γ-secretase modulators for Alzheimer's disease. RSC Medicinal Chemistry 11:9, pages 1003-1022.
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Pengju Nie, Abhishek Vartak & Yue-Ming Li. (2020) γ-Secretase inhibitors and modulators: Mechanistic insights into the function and regulation of γ-Secretase. Seminars in Cell & Developmental Biology 105, pages 43-53.
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Dileep Vijayan & Remya Chandra. (2020) Amyloid Beta Hypothesis in Alzheimer's Disease: Major Culprits and Recent Therapeutic Strategies. Current Drug Targets 21:2, pages 148-166.
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Nalini Schaduangrat, Veda Prachayasittikul, Saowapak Choomwattana, Prapimpun Wongchitrat, Kamonrat Phopin, Wilasinee Suwanjang, Aijaz Ahmad Malik, Bruno Vincent & Chanin Nantasenamat. (2019) Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease. Medicinal Research Reviews 39:5, pages 1730-1778.
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Guilherme Martins Silva, Mariana Pegrucci Barcelos, João Gabriel Curtolo Poiani, Lorane Izabel da Silva Hage‐Melim & Carlos Henrique Tomich de Paula da Silva. (2019) Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review. ChemMedChem 14:16, pages 1467-1483.
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Douglas S. Johnson, Yue-Ming Li, Martin Pettersson & Peter H. St George-Hyslop. (2017) Structural and Chemical Biology of Presenilin Complexes. Cold Spring Harbor Perspectives in Medicine 7:12, pages a024067.
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Matthew G. Bursavich, Bryce A. Harrison, Raksha Acharya, Donald E. Costa, Emily A. Freeman, Hilliary E. Hodgdon, Lori A. Hrdlicka, Hong Jin, Sudarshan Kapadnis, Jeffrey S. Moffit, Deirdre A. Murphy, Scott Nolan, Holger Patzke, Cuyue Tang, Melody Wen, Gerhard Koenig, Jean-François Blain & Duane A. Burnett. (2017) Design, Synthesis, and Evaluation of a Novel Series of Oxadiazine Gamma Secretase Modulators for Familial Alzheimer’s Disease. Journal of Medicinal Chemistry 60:6, pages 2383-2400.
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Douglas S. Johnson & Martin Pettersson. 2017. Alzheimer’s Disease II. Alzheimer’s Disease II 87 118 .
Akanksha Kulshreshtha & Poonam Piplani. (2016) Current pharmacotherapy and putative disease-modifying therapy for Alzheimer’s disease. Neurological Sciences 37:9, pages 1403-1435.
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Matthew G. Bursavich, Bryce A. Harrison & Jean-François Blain. (2016) Gamma Secretase Modulators: New Alzheimer’s Drugs on the Horizon?. Journal of Medicinal Chemistry 59:16, pages 7389-7409.
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Takafumi Takai, Tatsuki Koike, Minoru Nakamura, Yuichi Kajita, Toshiro Yamashita, Naohiro Taya, Tetsuya Tsukamoto, Tomomichi Watanabe, Koji Murakami, Tomoko Igari & Makoto Kamata. (2016) Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators (Part 2). Bioorganic & Medicinal Chemistry 24:14, pages 3192-3206.
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Christel A.S. Bergström, William N. Charman & Christopher J.H. Porter. (2016) Computational prediction of formulation strategies for beyond-rule-of-5 compounds. Advanced Drug Delivery Reviews 101, pages 6-21.
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Dai Lu, Han-Xun Wei, Jing Zhang, Yongli Gu, Pamela Osenkowski, Wenjuan Ye, Dennis J. Selkoe, Michael S. Wolfe & Corinne E. Augelli-Szafran. (2016) Part 1: Notch-sparing γ-secretase inhibitors: The identification of novel naphthyl and benzofuranyl amide analogs. Bioorganic & Medicinal Chemistry Letters 26:9, pages 2129-2132.
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Takafumi Takai, Yasutaka Hoashi, Yoshihide Tomata, Sachie Morimoto, Minoru Nakamura, Tomomichi Watanabe, Tomoko Igari & Tatsuki Koike. (2015) Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 25:19, pages 4245-4249.
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Takafumi Takai, Tatsuki Koike, Eiji Honda, Yuichi Kajita, Minoru Nakamura, Sachie Morimoto, Yasutaka Hoashi, Makoto Kamata, Tomomichi Watanabe, Tomoko Igari & Jun Terauchi. (2015) Design and synthesis of piperazine derivatives as a novel class of γ-secretase modulators that selectively lower Aβ42 production. Bioorganic & Medicinal Chemistry 23:9, pages 1923-1934.
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Xian Zhang, Yanfang Li, Huaxi Xu & Yun-wu Zhang. (2014) The γ-secretase complex: from structure to function. Frontiers in Cellular Neuroscience 8.
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Zhi-Ying Yang, Jian-Ming Li, Ling Xiao, Lin Mou, Yan Cai, He Huang, Xue-Gang Luo & Xiao-Xin Yan. (2014) [ 3 H]-L685,458 Binding Sites are Abundant in Multiple Peripheral Organs in Rats: Implications for Safety Assessment of Putative γ-Secretase Targeting Drugs . Basic & Clinical Pharmacology & Toxicology 115:6, pages 518-526.
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Martin Pettersson, Douglas S. Johnson, Chakrapani Subramanyam, Kelly R. Bales, Christopher W. am Ende, Benjamin A. Fish, Michael E. Green, Gregory W. Kauffman, Patrick B. Mullins, Thayalan Navaratnam, Subas M. Sakya, Cory M. Stiff, Tuan P. Tran, Longfei Xie, Liming Zhang, Leslie R. Pustilnik, Beth C. Vetelino, Kathleen M. Wood, Nikolay Pozdnyakov, Patrick R. Verhoest & Christopher J. O’Donnell. (2014) Design, Synthesis, and Pharmacological Evaluation of a Novel Series of Pyridopyrazine-1,6-dione γ-Secretase Modulators. Journal of Medicinal Chemistry 57:3, pages 1046-1062.
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Adrian Hall & Toshal R. Patel. 2014. 101 145 .
Nady Braidy, Anne Poljak, Tharusha Jayasena & Perminder Sachdev. 2014. Handbook of Neurotoxicity. Handbook of Neurotoxicity 1173 1190 .
Jian Jeffrey Chen, Wenyuan Qian, Kaustav Biswas, Chester Yuan, Albert Amegadzie, Qingyian Liu, Thomas Nixey, Joe Zhu, Mqhele Ncube, Robert M. Rzasa, Frank ChavezJr.Jr., Ning Chen, Frenel DeMorin, Shannon Rumfelt, Christopher M. Tegley, Jennifer R. Allen, Stephen Hitchcock, Randy Hungate, Michael D. Bartberger, Leeanne Zalameda, Yichin Liu, John D. McCarter, Jianhua Zhang, Li Zhu, Safura Babu-Khan, Yi Luo, Jodi Bradley, Paul H. Wen, Darren L. Reid, Frank Koegler, Charles DeanJr.Jr., Dean Hickman, Tiffany L. Correll, Toni Williamson & Stephen Wood. (2013) Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease. Bioorganic & Medicinal Chemistry Letters 23:23, pages 6447-6454.
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Christina J. Crump, Douglas S. Johnson & Yue-Ming Li. (2013) Development and Mechanism of γ-Secretase Modulators for Alzheimer’s Disease. Biochemistry 52:19, pages 3197-3216.
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Nikolay Pozdnyakov, Heather E. Murrey, Christina J. Crump, Martin Pettersson, T.Eric Ballard, Christopher W. am Ende, Kwangwook Ahn, Yue-Ming Li, Kelly R. Bales & Douglas S. Johnson. (2013) γ-Secretase Modulator (GSM) Photoaffinity Probes Reveal Distinct Allosteric Binding Sites on Presenilin. Journal of Biological Chemistry 288:14, pages 9710-9720.
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Ulrika Yngve, Kim Paulsen, Istvan Macsari, Marie Sundström, Ellen Santangelo, Christian Linde, Krisztian Bogar, Fredrik Lake, Yevgeni Besidski, Jonas Malmborg, Kia Strömberg, Paulina Appelkvist, Ann-Cathrine Radesäter, Fredrik Olsson, Daniel Bergström, Rebecka Klintenberg & Per I. Arvidsson. (2013) Triazolopyrimidinones as γ-secretase modulators: structure–activity relationship, modulator profile, and in vivo profiling. MedChemComm 4:2, pages 422.
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Francois Bischoff, Didier Berthelot, Michel De Cleyn, Gregor Macdonald, Garrett Minne, Daniel Oehlrich, Serge Pieters, Michel Surkyn, Andrés A. Trabanco, Gary Tresadern, Sven Van Brandt, Ingrid Velter, Mirko Zaja, Herman Borghys, Chantal Masungi, Marc Mercken & Harrie J. M. Gijsen. (2012) Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators. Journal of Medicinal Chemistry 55:21, pages 9089-9106.
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Christina J. Crump, Suita V. Castro, Feng Wang, Nikolay Pozdnyakov, T. Eric Ballard, Sangram S. Sisodia, Kelly R. Bales, Douglas S. Johnson & Yue-Ming Li. (2012) BMS-708,163 Targets Presenilin and Lacks Notch-Sparing Activity. Biochemistry 51:37, pages 7209-7211.
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S. N. Ozudogru & C. F. Lippa. (2012) Disease Modifying Drugs Targeting β-Amyloid. American Journal of Alzheimer's Disease & Other Dementiasr 27:5, pages 296-300.
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Yasong Lu, David Riddell, Eva Hajos-Korcsok, Kelly Bales, Kathleen M. Wood, Charles E. Nolan, Ashley E. Robshaw, Liming Zhang, Louis Leung, Stacey L. Becker, Elaine Tseng, Jason Barricklow, Emily H. Miller, Sarah Osgood, Brian T. O'Neill, Michael A. Brodney, Douglas S. Johnson & Martin Pettersson. (2012) Cerebrospinal Fluid Amyloid-β (Aβ) as an Effect Biomarker for Brain Aβ Lowering Verified by Quantitative Preclinical Analyses. Journal of Pharmacology and Experimental Therapeutics 342:2, pages 366-375.
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Antonia F. Stepan, Chakrapani Subramanyam, Ivan V. Efremov, Jason K. Dutra, Theresa J. O’Sullivan, Kenneth J. DiRico, W. Scott McDonald, Annie Won, Peter H. Dorff, Charles E. Nolan, Stacey L. Becker, Leslie R. Pustilnik, David R. Riddell, Gregory W. Kauffman, Bethany L. Kormos, Liming Zhang, Yasong Lu, Steven H. Capetta, Michael E. Green, Kapil Karki, Evelyn Sibley, Kevin P. Atchison, Andrew J. Hallgren, Christine E. Oborski, Ashley E. Robshaw, Blossom Sneed & Christopher J. O’Donnell. (2012) Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor. Journal of Medicinal Chemistry 55:7, pages 3414-3424.
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Martin Pettersson, Douglas S. Johnson, Chakrapani Subramanyam, Kelly R. Bales, Christopher W. am Ende, Benjamin A. Fish, Michael E. Green, Gregory W. Kauffman, Ricardo Lira, Patrick B. Mullins, Thayalan Navaratnam, Subas M. Sakya, Cory M. Stiff, Tuan P. Tran, Beth C. Vetelino, Longfei Xie, Liming Zhang, Leslie R. Pustilnik, Kathleen M. Wood & Christopher J. O’Donnell. (2012) Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 22:8, pages 2906-2911.
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Zhong-Yue Sun, Theodros Asberom, Thomas Bara, Chad Bennett, Duane Burnett, Inhou Chu, John Clader, Mary Cohen-Williams, David Cole, Michael Czarniecki, James Durkin, Gioconda Gallo, William Greenlee, Hubert Josien, Xianhai Huang, Lynn Hyde, Nicholas Jones, Irina Kazakevich, Hongmei Li, Xiaoxiang Liu, Julie Lee, Malcolm MacCoss, Mihir B. Mandal, Troy McCracken, Amin Nomeir, Robert Mazzola, Anandan Palani, Eric M. Parker, Dmitri A. Pissarnitski, Jun Qin, Lixin Song, Giuseppe Terracina, Monica Vicarel, Johannes Voigt, Ruo Xu, Lili Zhang, Qi Zhang, Zhiqiang Zhao, Xiaohong Zhu & Zhaoning Zhu. (2011) Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo. Journal of Medicinal Chemistry 55:1, pages 489-502.
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Christine E. Oborski, Rathna Iyer, Bruce A. Maguire, Gary Bora, Kevin Atchison, Nikolay Pozdnyakov, Kathleen Wood, Christine Parker, Timothy A. Subashi, Martin Pettersson, Douglas S. Johnson & Kelly R. Bales. (2012) Pharmacological Assessment of <i>γ</i>-Secretase Activity from Rodent and Human Brain. Neuroscience and Medicine 03:02, pages 149-161.
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Hui Wang, Andrea Megill, Kaiwen He, Alfredo Kirkwood & Hey-Kyoung Lee. (2012) Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity. Neural Plasticity 2012, pages 1-24.
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Christina J. Crump, Benjamin A. Fish, Suita V. Castro, De-Ming Chau, Natalya Gertsik, Kwangwook Ahn, Cory Stiff, Nikolay Pozdnyakov, Kelly R. Bales, Douglas S. Johnson & Yue-Ming Li. (2011) Piperidine Acetic Acid Based γ-Secretase Modulators Directly Bind to Presenilin-1. ACS Chemical Neuroscience 2:12, pages 705-710.
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Zhili Xin, Hairuo Peng, Andrew Zhang, Tina Talreja, Gnanasambandam Kumaravel, Lin Xu, Ellen Rohde, Mi-yong Jung, Melanie N. Shackett, David Kocisko, Sowmya Chollate, Anthone W. Dunah, Pamela A. Snodgrass-Belt, H. Moore Arnold, Arthur G. Taveras, Kenneth J. Rhodes & Robert H. Scannevin. (2011) Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach. Bioorganic & Medicinal Chemistry Letters 21:24, pages 7277-7280.
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Thomas Lübbers, Alexander Flohr, Synese Jolidon, Pascale David-Pierson, Helmut Jacobsen, Laurence Ozmen & Karlheinz Baumann. (2011) Aminothiazoles as γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 21:21, pages 6554-6558.
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