{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:42:45Z","timestamp":1789843365768,"version":"4.0.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"am","delay-in-days":331,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA14617 R01NS076517"],"award-info":[{"award-number":["AA14617 R01NS076517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA-043204"],"award-info":[{"award-number":["DA-043204"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000165","name":"Division of Chemistry","doi-asserted-by":"publisher","award":["CHE-1625735"],"award-info":[{"award-number":["CHE-1625735"]}],"id":[{"id":"10.13039\/100000165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006817","name":"University of Wisconsin-Milwaukee","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006817","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1016\/j.bmcl.2022.128637","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T04:17:07Z","timestamp":1645589827000},"page":"128637","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["Rationalizing the binding and \u03b1 subtype selectivity of synthesized imidazodiazepines and benzodiazepines at GABAA receptors by using molecular docking studies"],"prefix":"10.1016","volume":"62","author":[{"given":"Lalit K","family":"Golani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md","family":"Yeunus Mian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taukir","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal P","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithu","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishary","family":"Sharmin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Rezvanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Witkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2022.128637_b0005","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S0968-0004(02)02092-3","article-title":"Anxiety over GABA(A) receptor structure relieved by AChBP","volume":"27","author":"Cromer","year":"2002","journal-title":"Trends Biochem Sci."},{"key":"10.1016\/j.bmcl.2022.128637_b0010","doi-asserted-by":"crossref","first-page":"795","DOI":"10.2174\/1568026023393507","article-title":"Subunit composition, distribution and function of GABA(A) receptor subtypes","volume":"2","author":"Sieghart","year":"2002","journal-title":"Curr Top Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0015","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0197-0186(99)00045-5","article-title":"Structure and subunit composition of GABA(A) receptors","volume":"34","author":"Sieghart","year":"1999","journal-title":"Neurochem Int."},{"key":"10.1016\/j.bmcl.2022.128637_b0020","first-page":"217","article-title":"Heterogeneity of GABAA receptorsrevived interest in the development of subtype-selective drugs","volume":"5","author":"Sieghart","year":"2005","journal-title":"Curr Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0025","doi-asserted-by":"crossref","unstructured":"Clayton T, Chen JL, Ernst M, Richter L, Cromer BA, Morton CJNgH, Kaczorowski CC, Helmstetter FJ, Furtmuller R, Ecker G, Parker MW, Sieghart W, Cook JM. An updated unified pharmacophore model of the benzodiazepine binding site on gamma-aminobutyric acid(a) receptorscorrelation with comparative models. Curr Med Chem. 2007;142755. 10.2174\/092986707782360097.","DOI":"10.2174\/092986707782360097"},{"key":"10.1016\/j.bmcl.2022.128637_b0030","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/1047-2797(94)00112-7","article-title":"Risk of traffic accident injury after a prescription for a benzodiazepine","volume":"5","author":"Neutel","year":"1995","journal-title":"Ann Epidemiol."},{"key":"10.1016\/j.bmcl.2022.128637_b0035","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.annepidem.2007.03.009","article-title":"Risk of road traffic accidents associated with the prescription of drugsa registry-based cohort study","volume":"17","author":"Engeland","year":"2007","journal-title":"Ann Epidemiol."},{"key":"10.1016\/j.bmcl.2022.128637_b0040","article-title":"GABAA receptor subtype-selective modulators. I. alpha2\/alpha3-selective agonists as non-sedating anxiolytics","author":"Atack","year":"2011111176","journal-title":"Curr Top Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0045","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1212\/WNL.0000000000007271","article-title":"Photosensitive epilepsyRobust clinical efficacy of a selective GABA potentiator","volume":"92","author":"Gurrell","year":"2019","journal-title":"Neurology"},{"key":"10.1016\/j.bmcl.2022.128637_b0050","doi-asserted-by":"crossref","first-page":"10800","DOI":"10.1021\/acs.jmedchem.6b01332","article-title":"Synthesis and characterization of a novel \u03b3-aminobutyric acid type A (GABAA) receptor ligand that combines outstanding metabolic stability, pharmacokinetics, and anxiolytic efficacy","volume":"9","author":"Poe","year":"2016","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0055","doi-asserted-by":"crossref","unstructured":"Witkin JM, Cerne R, Davis PG, Freeman KB, do Carmo JM, Rowlett JK, Methuku KR, Okun A, Gleason S. Li X, Krambis MJ, Poe M, Li G, Schkeryantz JM, Jahan R, Yang L, Guo W, Golani LK, Anderson WH, Catlow JT, Jones TM, Porreca F, Smith JL, Knopp KL, Cook JM. The alpha2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats. Pharmacol Biochem Behav. 2019;180:22. 10.1016\/j.pbb.2019.02.013.","DOI":"10.1016\/j.pbb.2019.02.013"},{"key":"10.1016\/j.bmcl.2022.128637_b0060","doi-asserted-by":"crossref","DOI":"10.1146\/annurev-pharmtox-010919-023545","article-title":"Cryo-electron microscopymoving beyond x-ray crystal structures for drug receptors and drug development","volume":"60","author":"Garc\u00eda-Nafr\u00eda","year":"2020","journal-title":"Annu Rev Pharmacol."},{"key":"10.1016\/j.bmcl.2022.128637_b0065","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41586-018-0833-4","article-title":"Cryo-EM structure of the human alpha1beta3gamma2 GABAA receptor in a lipid bilayer","volume":"565","author":"Laverty","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2022.128637_b0070","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41422-018-0077-8","article-title":"Cryo-EM structure of the human alpha5beta3 GABAA receptor","volume":"28","author":"Liu","year":"2018","journal-title":"Cell Res."},{"key":"10.1016\/j.bmcl.2022.128637_b0075","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.39383","article-title":"Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA","volume":"7","author":"Phulera","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.bmcl.2022.128637_b0080","article-title":"Structure of a human synaptic GABA A receptor","volume":"55967","author":"Zhu","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2022.128637_b0085","article-title":"GABAA receptor signalling mechanisms revealed by structural pharmacology","volume":"565454","author":"Masiulis","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2022.128637_b0090","doi-asserted-by":"crossref","unstructured":"Wongsamitkul N, Maldifassi MC, Simeone X, Baur R, Ernst M, Sigel E. \u03b1 subunits in GABAA receptors are dispensable for GABA and diazepam action. Sci Rep. 2017;7 15498. 10.1038\/s41598-017-15628-7.","DOI":"10.1038\/s41598-017-15628-7"},{"key":"10.1016\/j.bmcl.2022.128637_b0095","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/00003246-199602000-00004","article-title":"Use of flumazenil in the treatment of drug overdosea double-blind and open clinical study in 110 patients","volume":"24","author":"Weinbroum","year":"1996","journal-title":"Crit Care Med."},{"key":"10.1016\/j.bmcl.2022.128637_b0100","doi-asserted-by":"crossref","unstructured":"Smith JL, Ping X, Jin X, Golani LK, Li G, Rashid F, Jahan R, Cook JM, Witkin JM. The positive allosteric modulator of alpha-2\/3-containing \u03b3-aminobutyric acid type a receptors, KRM-II-81, is active in pharmacoresistant models of epilepsy and in human epileptic tissue. Neurosurgery 2019;66 (Supplement_1). 10.1093\/neuros\/nyz310_697.","DOI":"10.1093\/neuros\/nyz310_697"},{"key":"10.1016\/j.bmcl.2022.128637_b0105","article-title":"An antidepressant-related pharmacological signature for positive allosteric modulators of alpha2\/3-containing GABAA receptors","author":"Methuku","year":"20181709","journal-title":"Pharmacol Biochem Behav."},{"key":"10.1016\/j.bmcl.2022.128637_b0110","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/acer.14000","article-title":"GABAA receptor subtypes and the abuse-related effects of ethanol in rhesus monkeysexperiments with selective positive allosteric modulators","volume":"43","author":"Berro","year":"2019","journal-title":"Alcohol Clin Exp Res."},{"key":"10.1016\/j.bmcl.2022.128637_b0115","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/FBP.0000000000000464","article-title":"Effects of the \u03b12\/\u03b13-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 on pain-depressed behavior in ratscomparison with ketorolac and diazepam","volume":"30","author":"Moerke","year":"2019","journal-title":"Behav Pharmacol."},{"key":"10.1016\/j.bmcl.2022.128637_b0120","article-title":"The positive allosteric modulator of alpha2\/3-containing GABAA receptors, KRM-II-81, is active in pharmaco-resistant models of epilepsy and reduces hyperexcitability after traumatic brain injury","author":"Witkin","year":"2019","journal-title":"J Pharmacol Exp Ther."},{"key":"10.1016\/j.bmcl.2022.128637_b0125","article-title":"Novel imidazobenzodiazepine GABAA receptor alpha 2\/alpha 3 selective PAM for the treatment of refractory\/resistance epilepsy","volume":"257","author":"Golani","year":"2019","journal-title":"In Abstrt Pap Am Chem S. American Chemical SocietyOrlando, Florida"},{"key":"10.1016\/j.bmcl.2022.128637_b0130","unstructured":"Ciardiello F, Tortora G. A novel approach in the treatment of cancertargeting the epidermal growth factor receptor. Clin Cancer Res. 2001;72958. PMID11595683."},{"key":"10.1016\/j.bmcl.2022.128637_b0135","article-title":"Structures of lung cancer-derived EGFR mutants and inhibitor complexesmechanism of activation and insights into differential inhibitor sensitivity","volume":"11217","author":"Yun","year":"2007","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bmcl.2022.128637_b0140","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1042\/BJ20121513","article-title":"Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain","volume":"448","author":"Park","year":"2012","journal-title":"Biochem J."},{"key":"10.1016\/j.bmcl.2022.128637_b0145","article-title":"Lu T.1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2-p53 interactiondiscovery and SAR","author":"Parks","year":"200515765","journal-title":"Bioorg Med Chem Lett."},{"key":"10.1016\/j.bmcl.2022.128637_b0150","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1021\/acschembio.5b00515","article-title":"experimental and theoretical evaluation of the ethynyl moiety as a halogen bioisostere","volume":"10","author":"Wilcken","year":"2015","journal-title":"ACS Chem Biol."},{"key":"10.1016\/j.bmcl.2022.128637_b0155","first-page":"A1","article-title":"Preparation of substituted benzo[f]\u200bimidazo[1,\u200b5-\u200ba]\u200b[1,\u200b4]\u200bdiazepine-\u200b3-\u200bcarboxamides as \u03b15-\u200bcontaining GABAA receptor agonists for treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders","volume":"2017161370","author":"Cook","year":"2017","journal-title":"WO"},{"key":"10.1016\/j.bmcl.2022.128637_b0160","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2014.01.036","article-title":"Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptorsthe approximated activation of receptor subtypes may explain behavioral effects","volume":"1554","author":"Obradovic","year":"2014","journal-title":"Brain Res."},{"key":"10.1016\/j.bmcl.2022.128637_b0165","first-page":"B2","article-title":"Anxiolytic agents with reduced sedative and ataxic effects","volume":"7119196","author":"Cook","year":"2006","journal-title":"US"},{"key":"10.1016\/j.bmcl.2022.128637_b0170","unstructured":"Cook JM, Huang S, Edwankar R, Namjoshi OA, Wang ZJ. Selective agents for pain suppression. US8835424 B2, 2014."},{"key":"10.1016\/j.bmcl.2022.128637_b0175","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1055\/s-0037-1610211","article-title":"Improved synthesis of anxiolytic, anticonvulsant, and antinociceptive \u03b12\/\u03b13-gaba(a)-ergic receptor subtype selective ligands as promising agents to treat anxiety, epilepsy, and neuropathic pain","volume":"50","author":"Li","year":"2018","journal-title":"Synthesis"},{"key":"10.1016\/j.bmcl.2022.128637_b0180","article-title":"A review of the updated pharmacophore for the alpha 5 gaba(a) benzodiazepine receptor model. Int","volume":"430248","author":"Clayton","year":"2015","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0185","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ejphar.2016.09.016","article-title":"Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the alpha5 subunit","volume":"791","author":"Stamenic","year":"2016","journal-title":"Eur J Pharmacol."},{"key":"10.1016\/j.bmcl.2022.128637_b0190","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1021\/jm950887n","article-title":"Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepineshigh-affinity, selective probes for alpha 5-containing GABAA receptors","volume":"39","author":"Liu","year":"1996","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmcl.2022.128637_b0195","article-title":"Modulating native GABAA receptors in medulloblastoma with positive allosteric benzodiazepine-derivatives induces cell death","author":"Kallay","year":"2019142411","journal-title":"J Neurooncol."},{"key":"10.1016\/j.bmcl.2022.128637_b0200","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1166\/jbn.2016.2262","article-title":"First in vivo testing of compounds targeting Group 3 medulloblastomas using an implantable microdevice as a new paradigm for drug development","volume":"12","author":"Jonas","year":"2016","journal-title":"J Biomed Nanotechnol."},{"key":"10.1016\/j.bmcl.2022.128637_b0205","first-page":"A1","article-title":"Preparation of benzodiazepines, in particular 1,4-benzodiazepines, as anxiolytic and anticonvulsant agents with reduced sedative and ataxic effects","volume":"20060003995","author":"Cook","year":"2006","journal-title":"US"},{"key":"10.1016\/j.bmcl.2022.128637_b0210","article-title":"Pharmacology of recombinant \u03b3-aminobutyric acidA receptors rendered diazepam-insensitive by point-mutated \u03b1-subunits","volume":"431","author":"Benson","year":"1989","journal-title":"FEBS Lett."}],"container-title":["Bioorganic & Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X22001135?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X22001135?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:44:36Z","timestamp":1760773476000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X22001135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":42,"alternative-id":["S0960894X22001135"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2022.128637","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rationalizing the binding and \u03b1 subtype selectivity of synthesized imidazodiazepines and benzodiazepines at GABAA receptors by using molecular docking studies","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2022.128637","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"128637"}}