{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:36:00Z","timestamp":1776465360362,"version":"3.51.2"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T00:00:00Z","timestamp":1410998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Ministry of Science and Technology of the Republic of China","award":["NSC 100-2320-B-182A-006-"],"award-info":[{"award-number":["NSC 100-2320-B-182A-006-"]}]},{"name":"Ministry of Science and Technology of the Republic of China","award":["MOST 103-2113-M-039-003-"],"award-info":[{"award-number":["MOST 103-2113-M-039-003-"]}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GVK Biosciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Four new pentacyclic benzodiazepine derivatives (PBDTs 13\u201316) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.<\/jats:p>","DOI":"10.3390\/ijms150916500","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T11:47:31Z","timestamp":1411040851000},"page":"16500-16510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Synthesis, Anticonvulsant, Sedative and Anxiolytic Activities of Novel Annulated Pyrrolo[1,4]benzodiazepines"],"prefix":"10.3390","volume":"15","author":[{"given":"Kumaraswamy","family":"Sorra","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Laboratory, Gunapati Venkata Krishnareddy Biosciences Private Limited, Plot No. 28A, Industrial Development Area Nacharam, Hyderabad 500076, India"},{"name":"Chemistry Division, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500085, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Shu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung   40402,   Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Fen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, China Medical University, Taichung   40402,   Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas","family":"Pusuluri","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Gunapati Venkata Krishnareddy Biosciences Private Limited, Plot No. 28A, Industrial Development Area Nacharam, Hyderabad 500076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khagga","family":"Mukkanti","sequence":"additional","affiliation":[{"name":"Chemistry Division, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500085, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-5035","authenticated-orcid":false,"given":"Chi-Rei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources,  China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-9366","authenticated-orcid":false,"given":"Ta-Hsien","family":"Chuang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung   40402,   Taiwan"},{"name":"Research Center for Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1126\/science.918669","article-title":"Benzodiazepine receptor: Demonstration in the central nervous system","volume":"198","author":"Mohler","year":"1977","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ejphar.2004.06.036","article-title":"Altered response to benzodiazepine anxiolytics in mice lacking GABAB(1) receptors","volume":"497","author":"Mombereau","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ejphar.2004.07.043","article-title":"Anxioselective anxiolytics: Can less be more?","volume":"500","author":"Basile","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1074\/jbc.M311371200","article-title":"On the benzodiazepine binding pocket in GABAA receptors","volume":"279","author":"Berezhnoy","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0091-3057(82)90441-5","article-title":"GABA mediation of the anti-aversive action of minor tranquilizers","volume":"16","author":"Graeff","year":"1982","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0960-894X(02)00262-7","article-title":"A concise route to triazolobenzodiazepine derivatives via a one-pot alkyne-azide cycloaddition reaction","volume":"12","author":"Thomas","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/S0040-4039(03)00078-9","article-title":"The isolation and use of a benzodiazepine iminochloride for the efficient construction of flumazenil","volume":"44","author":"Spurr","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14803","DOI":"10.1016\/S0040-4020(99)00944-8","article-title":"A facile synthesis of flumazenil analogues","volume":"55","author":"Broggini","year":"1999","journal-title":"Tetrahedron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1021\/jm00060a007","article-title":"Synthesis and evaluation of imidazo[1,5-a][1,4]benzodiazepine esters with high affinities and selectivities at \u201cdiazepam-insensitive\u201d benzodiazepine receptors","volume":"36","author":"Gu","year":"1993","journal-title":"J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/j.1528-1157.1993.tb02146.x","article-title":"Effects of a benzodiazepine, bretazenil (Ro 16-6028), on rhythmic metrazol EEG activity: Comparison with standard anticonvulsants","volume":"34","year":"1993","journal-title":"Epilepsia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Neidle, D., and Waring, M.J. (1993). Molecular Aspects of Anticancer Drug DNA Interactions, The Macmillan Press Ltd.","DOI":"10.1007\/978-1-349-12356-8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/199501a0","article-title":"\u201cRefuin\u201d: A non-cytotoxic carcinostatic compound proliferated by a thermophilic actinomycete","volume":"199","author":"Tendler","year":"1963","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/282529a0","article-title":"Proposed structure of the anthramycin\u2013DNA adduct","volume":"282","author":"Hurley","year":"1979","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Neidle, S., and Waring, M.J. (1993). Molecular Aspects of Anticancer Drug-DNA Interactions, The Macmillan Press Ltd.","DOI":"10.1007\/978-1-349-12356-8"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Broggini, G., de Marchi, I., Martinelli, M., Paladino, G., Pilati, T., and Terraneo, A. (2005). Effective synthesis of enantiopure [1,2,3]triazolo[1,5-a]- and pyrazolo[1,5-a]-pyrrolo[2,1-c][1,4]benzodiazepines by diastereoselective intramolecular azide and nitrilimine cycloadditions. Synthesis, 2246\u20132252.","DOI":"10.1055\/s-2005-869991"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2533\/chimia.1993.141","article-title":"Benzodiazepines, the story of the antagonist flumazenil and of the partial agonist bretazenil","volume":"47","author":"Hunkeler","year":"1993","journal-title":"Chimia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.7164\/antibiotics.38.1633","article-title":"Asperlicin, a novel non-peptidal cholecystokinin antagonist from Aspergillus alliaceus","volume":"38","author":"Goetz","year":"1985","journal-title":"J. Antibiot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.2994227","article-title":"A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus","volume":"230","author":"Chang","year":"1985","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/np980511n","article-title":"Sclerotigenin: A New antiinsectan benzodiazepine from the sclerotia of Penicillium sclerotigenum","volume":"62","author":"Joshi","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1021\/np000381u","article-title":"Circumdatin G, a new alkaloid from the fungus Aspergillus ochraceus","volume":"64","author":"Dai","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1021\/np980495u","article-title":"Circumdatins D, E, and F: Further fungal benzodiazepine analogues from Aspergillus ochraceus","volume":"62","author":"Breinholt","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1021\/jo800348d","article-title":"Structure revision of circumdatins A and B, benzodiazepine alkaloids produced by marine fungus Aspergillus ostianus, by X-ray crystallography","volume":"73","author":"Ookura","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1021\/jo981536u","article-title":"Circumdatin A, B, and C: Three new benzodiazepine alkaloids isolated from a culture of the fungus Aspergillus ochraceus","volume":"64","author":"Breinholt","year":"1999","journal-title":"J. Org. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1021\/jm00160a024","article-title":"Cholecystokinin antagonists. Synthesis of asperlicin analogs with improved potency and water solubility","volume":"29","author":"Bock","year":"1986","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"515","DOI":"10.7164\/antibiotics.47.515","article-title":"Benzomalvins, new substance P inhibitors from a Penicillium sp.","volume":"47","author":"Sun","year":"1994","journal-title":"J. Antibiot."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/ja.2005.54","article-title":"Circumdatin H, a new inhibitor of mitochondrial NADH oxidase, from Aspergillus ochraceus","volume":"58","author":"Gonzalez","year":"2005","journal-title":"J. Antibiot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.3390\/molecules17088762","article-title":"Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives","volume":"17","author":"Kumaraswamy","year":"2012","journal-title":"Molecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.tet.2011.12.032","article-title":"Palladium catalyzed synthesis of quinazolino [1,4] benzodiazepine alkaloids and analogous","volume":"68","author":"Kumaraswamy","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jhet.5570170410","article-title":"Action des isocyanates sur les benzisothiazol-2,1 ones-3 (1H) et sur les thiadiazol-1,2,4 ones-5: Un nouveau r\u00e9arrangement avec extrusion de l\u2019atome de soufre","volume":"17","author":"Perronnet","year":"1980","journal-title":"J. Heterocycl. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1021\/jm00166a023","article-title":"Preparation of triazolo[1,5-c]pyrimidines as potential antiasthma agents","volume":"33","author":"Medwid","year":"1990","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/1521-4184(200211)335:8<389::AID-ARDP389>3.0.CO;2-X","article-title":"Synthesis and antibacterial activity of fused 1,2,4-triazolo[4,3-a]quinoxaline and oxopyrimido[2',1':5,1]-1,2,4-triazolo[4,3-a]quinoxaline derivatives","volume":"335","author":"Nasr","year":"2002","journal-title":"Arch. Pharm."},{"key":"ref_32","first-page":"6","article-title":"Experimental modeling of anxiety","volume":"1","author":"Pathak","year":"2011","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jep.2013.09.023","article-title":"Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice","volume":"150","author":"Kebebew","year":"2013","journal-title":"J. Ethnopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/9\/16500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:16:03Z","timestamp":1760217363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/9\/16500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,18]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,9]]}},"alternative-id":["ijms150916500"],"URL":"https:\/\/doi.org\/10.3390\/ijms150916500","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,18]]}}}