{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:44:41Z","timestamp":1793159081206,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.bmc.2025.118535","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T04:53:55Z","timestamp":1766120035000},"page":"118535","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["New pyrazolo[1,5-a]pyrimidine derivatives as potential CDK2 inhibitors and apoptosis-driven antiproliferative agents"],"prefix":"10.1016","volume":"134","author":[{"given":"Ahmed Abd El-Hamed","family":"El-Rahmany","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia A.","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Nafie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagdy M.","family":"Eldehna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A.","family":"Abdel-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa S.A.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2025.118535_bb0005","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.bmc.2025.118535_bb0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108565","article-title":"Development of benzothiazole-grafted pyrazolo[1,5-a]pyrimidines as new CDK2 inhibitors and anti-prostate cancer agents","volume":"161","author":"Elkotamy","year":"2025","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0015","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1039\/D4RA07556K","article-title":"Advances in pyrazolo[1,5-a]pyrimidines: synthesis and their role as protein kinase inhibitors in cancer treatment","volume":"15","author":"Iorkula","year":"2025","journal-title":"RSC Adv"},{"key":"10.1016\/j.bmc.2025.118535_bb0020","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.drudis.2019.12.001","article-title":"Targeting CDK2 in cancer: challenges and opportunities for therapy","volume":"25","author":"Tadesse","year":"2020","journal-title":"Drug Discov Today"},{"key":"10.1016\/j.bmc.2025.118535_bb0025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2025.2475233","article-title":"Design, synthesis and biological evaluation of pyrazolo[3,4-b]pyridine derivatives as dual CDK2\/PIM1 inhibitors with potent anti-cancer activity and selectivity","author":"Elkotamy","year":"2025","journal-title":"J Biomol Struct Dyn"},{"key":"10.1016\/j.bmc.2025.118535_bb0030","doi-asserted-by":"crossref","first-page":"8508","DOI":"10.1021\/jm100732t","article-title":"A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration","volume":"53","author":"Heathcote","year":"2010","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0035","doi-asserted-by":"crossref","DOI":"10.1126\/science.abc1495","article-title":"CDK4 and CDK6 kinases: from basic science to cancer therapy","volume":"375","author":"Fassl","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.bmc.2025.118535_bb0040","series-title":"Specific CDK4 \/ 6 Inhibition in Breast Cancer: A Systematic Review of Current Clinical Evidence","first-page":"1","author":"Polk","year":"2017"},{"key":"10.1016\/j.bmc.2025.118535_bb0045","series-title":"CDK 4 \/ 6 Inhibitors as Single Agent in Advanced Solid Tumors","first-page":"1","volume":"8","author":"Schettini","year":"2018"},{"key":"10.1016\/j.bmc.2025.118535_bb0050","article-title":"Synthesis and in-vitro anti-proliferative evaluation of some pyrazolo [ 1 , 5- a ] pyrimidines as novel larotrectinib analogs","author":"Attia","year":"2019","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bioorg.2019.01.008","article-title":"Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity","volume":"86","author":"Ali","year":"2019","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105431","article-title":"Synthesis of a new series of pyrazolo[1,5-a]pyrimidines as CDK2 inhibitors and anti-leukemia","volume":"117","author":"Almehmadi","year":"2021","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ph17121667","article-title":"Design, synthesis and molecular modeling of pyrazolo[1,5-a]pyrimidine derivatives as dual inhibitors of CDK2 and TRKA kinases with anti-proliferative activity","volume":"17","author":"Attia","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.bmc.2025.118535_bb0070","doi-asserted-by":"crossref","first-page":"17601","DOI":"10.1039\/D5NJ02010G","article-title":"Targeting CDK2 and CDK7: rational design of pyrazolo[1,5-a]pyrimidine derivatives as potent anti-cancer agents","volume":"49","author":"Elbakry","year":"2025","journal-title":"New J Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0075","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jhet.5570310413","article-title":"The reaction of methyl 3-amino-4-cyano-5-methylthiothiophene-2-carboxylate with dmad. A new synthesis of polyfunctionalized quinolines","volume":"31","author":"Tominaga","year":"1994","journal-title":"J Heterocyclic Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0080","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1021\/jm021023m","article-title":"Design, synthesis, and biological evaluation of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists","volume":"46","author":"Baraldi","year":"2003","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0085","doi-asserted-by":"crossref","first-page":"10453","DOI":"10.1016\/j.tet.2009.10.021","article-title":"One-pot synthesis of new tetrasubstituted thiophenes and selenophenes","volume":"65","author":"Thomae","year":"2009","journal-title":"Tetrahedron"},{"key":"10.1016\/j.bmc.2025.118535_bb0090","doi-asserted-by":"crossref","first-page":"12187","DOI":"10.3390\/molecules171012187","article-title":"Synthesis and herbicidal activity of substituted pyrazole isothiocyanates","volume":"17","author":"Wu","year":"2012","journal-title":"Molecules"},{"key":"10.1016\/j.bmc.2025.118535_bb0095","doi-asserted-by":"crossref","first-page":"14036","DOI":"10.3390\/molecules190914036","article-title":"Design, synthesis and fungicidal activities of some novel pyrazole derivatives","volume":"19","author":"Liu","year":"2014","journal-title":"Molecules"},{"key":"10.1016\/j.bmc.2025.118535_bb0100","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ejmech.2012.09.031","article-title":"Synthesis of novel pyrazolo[3,4-d]pyrimidine derivatives as potential anti-breast cancer agents","volume":"57","author":"Abd El Hamid","year":"2012","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0105","first-page":"487","article-title":"Utilization of polymeric carriers for (E)-1-(5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)-3-(3,4,5-trimetho xyphenyl)prop-2-en-1-one as anti-cancer agent","volume":"67","author":"Mohamed","year":"2024","journal-title":"Egypt J Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0110","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4028\/www.scientific.net\/MSF.948.153","article-title":"Synthesis and activity test of coumarin-chalcone derivative as a colorimetric sensor for chicken spoilage Indicator","volume":"948","author":"Dehani","year":"2019","journal-title":"Mater Sci Forum"},{"key":"10.1016\/j.bmc.2025.118535_bb0115","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.4314\/ijbcs.v11i3.32","article-title":"Synthesis of novel thiazolobenzimidazoles","volume":"11","author":"Coulbali","year":"2017","journal-title":"Int J Biol Chem Sci"},{"key":"10.1016\/j.bmc.2025.118535_bb0120","series-title":"I. Screening, M.M. Studies, Accepted Manuscript","author":"Screening","year":"2018"},{"key":"10.1016\/j.bmc.2025.118535_bb0125","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.3390\/molecules15063775","article-title":"Thiazolo[3,2-a]benzimidazoles: synthetic strategies, chemical transformations and biological activities","volume":"15","author":"Al-Rashood","year":"2010","journal-title":"Molecules"},{"key":"10.1016\/j.bmc.2025.118535_bb0130","doi-asserted-by":"crossref","first-page":"6520","DOI":"10.1016\/j.bmc.2015.08.006","article-title":"Kinase hinge binding scaffolds and their hydrogen bond patterns","volume":"23","author":"Xing","year":"2015","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0135","first-page":"6","article-title":"Molecular docking analysis of N-[2-(3-Methylthio(1,2,4-Thiadiazol-5-Ylthio))acetyl] benzamide molecule with integrin and DNA","author":"Demet Demirag","year":"2021","journal-title":"Open J Nano-Aliye Demet DEM\u0130RAG Open J Nano"},{"key":"10.1016\/j.bmc.2025.118535_bb0140","doi-asserted-by":"crossref","DOI":"10.3390\/ph16111593","article-title":"Design, synthesis, in vitro, and in silico studies of new N5-substituted-pyrazolo[3,4-d]pyrimidinone derivatives as anti-cancer CDK2 inhibitors","volume":"16","author":"Zaki","year":"2023","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.bmc.2025.118535_bb0145","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202500028","article-title":"Marine-inspired Spirooxindole PIM-1 kinase inhibitors endowed with concomitant TRKA\/CDK2 inhibition for multifaceted non-small cell lung cancer apoptotic induction","author":"Al-Jassas","year":"2025","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bmc.2025.118535_bb0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108861","article-title":"Chalcone-inspired indole, carbazole, and phenothiazine hybrids as potent aldose reductase inhibitors with selective anti-cancer potential: rational design, synthesis, and multi-level characterization","volume":"164","author":"G\u00fcle\u00e7","year":"2025","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108689","article-title":"Fluorenyl-phthalimide hybrids as potent aldose reductase inhibitors with selective anti-cancer activity: rational design, synthesis, and molecular insights","volume":"163","author":"Gundogdu","year":"2025","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2025.118416","article-title":"Phthalimide\u2013benzoic acid hybrids as potent aldose reductase inhibitors: synthesis, enzymatic kinetics, and in silico characterization","volume":"131","author":"Hoti","year":"2025","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108788","article-title":"N-substituted phthalimide\u2013carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: synthesis, mechanistic insights, and cancer-relevant profiling","volume":"163","author":"Zognjani","year":"2025","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.105995","article-title":"Design and synthesis of novel benzoazoninone derivatives as potential CBSIs and apoptotic inducers: in vitro, in vivo, molecular docking, molecular dynamics, and SAR studies","volume":"127","author":"Hammouda","year":"2022","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115707","article-title":"Discovery of indolinone-bearing benzenesulfonamides as new dual carbonic anhydrase and VEGFR-2 inhibitors possessing anti-cancer and pro-apoptotic properties","volume":"259","author":"Saied","year":"2023","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0180","doi-asserted-by":"crossref","first-page":"10558","DOI":"10.1021\/acs.jmedchem.3c00721","article-title":"1,5-Diaryl-1,2,4-triazole Ureas as new SLC-0111 analogues endowed with dual carbonic anhydrase and VEGFR-2 inhibitory activities","volume":"66","author":"Elsawi","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0185","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107804","article-title":"Identification of indole-grafted pyrazolopyrimidine and pyrazolopyridine derivatives as new anti-cancer agents: synthesis, biological assessments, and molecular modeling insights","volume":"153","author":"Eldehna","year":"2024","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0190","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1080\/14756366.2022.2070744","article-title":"Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies","volume":"37","author":"Yousef","year":"2022","journal-title":"J Enzyme Inhib Med Chem"},{"key":"10.1016\/j.bmc.2025.118535_bb0195","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1107\/S0909049513020736","article-title":"Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity","volume":"20","author":"Fujino","year":"2013","journal-title":"J Synchrotron Radiat"},{"key":"10.1016\/j.bmc.2025.118535_bb0200","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2024.1467460","article-title":"Essential oils as capsule disruptors: enhancing antibiotic efficacy against multidrug-resistant Klebsiella pneumoniae","volume":"15","author":"El-Demerdash","year":"2024","journal-title":"Front Microbiol"},{"key":"10.1016\/j.bmc.2025.118535_bb0205","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252312949","article-title":"Natural inhibitors of salmonella MDR efflux pumps AcrAB and AcrD: an integrated in silico, molecular, and in vitro investigation","volume":"25","author":"El-Demerdash","year":"2024","journal-title":"Int J Mol Sci"}],"container-title":["Bioorganic & Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625004778?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625004778?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:32:54Z","timestamp":1769117574000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089625004778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":41,"alternative-id":["S0968089625004778"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118535","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"New pyrazolo[1,5-a]pyrimidine derivatives as potential CDK2 inhibitors and apoptosis-driven antiproliferative agents","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118535","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118535"}}