{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:04:20Z","timestamp":1784178260691,"version":"3.55.0"},"reference-count":120,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Pyrazole derivatives have attracted considerable interest in medicinal chemistry as adaptable frameworks for developing cholinesterase inhibitors, owing to their advantageous physicochemical properties and structural flexibility. The heteroaromatic characteristics of the pyrazole core allow for various substitution patterns, promoting selective interactions with both the catalytically active site (CAS) and the peripheral anionic site (PAS) of cholinesterase enzymes. These attributes enable pyrazole-based drugs to be viable candidates for the therapy of cognitive disorders, especially Alzheimer\u2019s disease. This study aims to systematically describe medicinal chemistry studies on pyrazole-based cholinesterase inhibitors conducted from 2020 to 2025. The focus is on structural alterations of the pyrazole core and their impact on the inhibitory action against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using structure\u2013activity relationship (SAR) analysis. Recent advancements in in vitro enzymatic inhibition studies, molecular docking, kinetic analysis, ADME predictions, and multi-target-directed ligand (MTDL) techniques are rigorously evaluated to elucidate trends in potency, selectivity, and drug-like characteristics based on information retrieved from three search engines: Scopus, PubMed, and Google Scholar. This review addresses significant challenges in pharmacokinetics, blood\u2013brain barrier permeability, and safety while delineating prospects for integrating rational design, computational modeling, and biological validation to expedite the development of clinically relevant pyrazole-based cholinesterase inhibitors for Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ph19071079","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:55:21Z","timestamp":1783990521000},"page":"1079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent Advances in Pyrazole-Based Cholinesterase Inhibitors: Medicinal Chemistry Perspectives from 2020 to 2025"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3643-2707","authenticated-orcid":false,"given":"Lalsu","family":"Yeysin","sequence":"first","affiliation":[{"name":"Institute of Science, Gazi University, Ankara 06500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7984-9159","authenticated-orcid":false,"given":"Deniz","family":"Ak\u0131n","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Gazi University, Teknikokullar, Ankara 06500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-1276","authenticated-orcid":false,"given":"S\u00fcleyman","family":"\u00c7al\u0131\u015fkan","sequence":"additional","affiliation":[{"name":"Department of Material Processing Technologies and Polymer Technology, K\u0131r\u0131kkale Vocational School, K\u0131r\u0131kkale University, K\u0131r\u0131kkale 71450, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7338-4015","authenticated-orcid":false,"given":"Elvan","family":"Hasano\u011flu \u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Gazi University, Teknikokullar, Ankara 06500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-7534","authenticated-orcid":false,"given":"Hamada","family":"Hashem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-5265","authenticated-orcid":false,"given":"Suleyman","family":"Akocak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ad\u0131yaman University, Ad\u0131yaman 02040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-3191","authenticated-orcid":false,"given":"Stefan","family":"Br\u00e4se","sequence":"additional","affiliation":[{"name":"Institute of Biological and Chemical Systems Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Servet","family":"\u00c7ete","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Gazi University, Teknikokullar, Ankara 06500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lamptey, R.N.L., Chaulagain, B., Trivedi, R., Gothwal, A., Layek, B., and Singh, J. 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