{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:08:57Z","timestamp":1791925737672,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T00:00:00Z","timestamp":1728172800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Alzheimer's disease (AD) is a chronic progressive, age\u2010related neurodegenerative brain disorder characterized by the irreversible decline of memory and other cognitive functions. It is one of the major health threat of the 21st century, which affects around 60% of the population over the age of 60\u2009years. The problem of this disease is even more major because the existing pharmacotherapies only provide symptomatic relief without addressing the basic factors of the disease. It is characterized by the extracellular deposition of amyloid \u03b2 (A\u03b2) to form senile plaques, and the intracellular hyperphosphorylation of tau to form neurofibrillary tangles (NFTs). Due to the complex pathophysiology of this disease, various hypotheses\u00a0have been proposed, including the cholinergic, A\u03b2, tau, oxidative stress, and the metal\u2013ion hypothesis. Among these, the cholinergic and A\u03b2 hypotheses are the primary targets for addressing AD. Therefore, continuous advances have been made in developing potential cholinesterase inhibitors and <jats:italic>N<\/jats:italic>\u2010methyl\u2010D\u2010aspartate (NMDA) receptor antagonists to delay disease progression and restore cholinergic neurotransmission. In this review article, we tried to comprehensively summarize the recent advancement in NMDA receptor antagonist (memantine) and their hybrid analogs as potential disease\u2010modifying agents for the treatment of AD. Furthermore, we also depicted the design, rationale, and SAR analysis of the memantine\u2010based hybrids used in the last decade for the treatment of AD.<\/jats:p>","DOI":"10.1111\/cbdd.14638","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:50:11Z","timestamp":1728262211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Recent Advances in Medicinal Chemistry of Memantine Against Alzheimer's Disease"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1535-2829","authenticated-orcid":false,"given":"Yash\u00a0Pal","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Himachal Pradesh Technical University  Hamirpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Himachal Pradesh Technical University  Hamirpur India"},{"name":"Government College of Pharmacy  Shimla India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jorganchem.2023.122742"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202300054"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00517"},{"issue":"20","key":"e_1_2_9_6_1","article-title":"The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to","volume":"21","author":"Bukke V. N.","year":"2020","journal-title":"Pharmacotherapy"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.10.014"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.28"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27061816"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010009\u20108104\u2010z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1980\u201057642009dn30300003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.06.123"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1174738"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010018\u20100107\u2010y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200398"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010170672"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061289"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115670"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001249\u20100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01940"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.03.084"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c11706"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14175"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.05.034"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1ra03718h"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23010230"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.17179\/excli2016\u2010820"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-409547-2.13766-7"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25102337"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14329"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.12.021"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116172"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2014.09.002"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.12.003"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00043"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00632"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arres.2022.100039"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108352"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003154.pub6"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.01.019"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010061010\u2010113613"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.66.2.137"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.07.051"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13922"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8416763"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.31661\/gmj.v3i1.100"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.07.011"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.10.060"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.02.039"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00530"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14318"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3009458"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010022\u201002565\u20100"},{"key":"e_1_2_9_54_1","volume-title":"Design, Synthesis, and Biological Evaluation of Ferulic Acid Template Based Naturally Inspired Novel Neuroprotective Multifunctional Molecules for the Treatment of Alzheimer's Disease","author":"Singh Y. P.","year":"2021"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14337"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22111"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14478"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22113"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00443"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030\u2010018\u20109878\u20104"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113278"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116385"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112257"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11172\u2010016\u20101461\u20105"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2013.02.013"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules18022397"},{"key":"e_1_2_9_67_1","first-page":"S356","article-title":"The Costs of Alzheimer's Disease and the Value of Effective Therapies","volume":"17","author":"Stefanacci R. G.","year":"2011","journal-title":"American Journal of Managed Care"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14133"},{"key":"e_1_2_9_69_1","unstructured":"Valverde Murillo E.2015.\u201cExploring Adamantine\u2010Like Scaffolds for a Wide Range of Therapeutic Targets.\u201dDoctoral Thesis."},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13905"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.5.4.16986"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.04.039"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14638","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:53:48Z","timestamp":1730814828000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":71,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/cbdd.14638"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14638","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14638"}}