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Specific Quantitative Structure Activity Relationship (QSAR) models were developed in Forge\u2122 for the prediction of biological activity (IC<jats:sub>50<\/jats:sub>) on the \u03b3\u2010aminobutyric acid A receptor (GABA\u2010AR) of previously identified classified and unclassified DBDZs. A set of new potential ligands resulting from scaffold hopping studies conducted with MOE<jats:sup>\u00ae<\/jats:sup> was also evaluated. Two generated QSAR models (i.e. 3D\u2010field QSAR and RVM) returned very good performance statistics (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.98 [both] and <jats:italic>q<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.75 and 0.72, respectively). The DBZDs predicted to be the most active were flubrotizolam, clonazolam, pynazolam and flucotizolam, consistently with what\u00a0reported in literature and\/or drug discussion fora. The scaffold hopping studies strongly suggest that replacement of the pendant phenyl moiety with a five\u2010membered ring could increase biological activity and highlight the existence of a still unexplored chemical space for DBZDs. QSAR could be of use as a preliminary risk assessment model for (newly) identified DBZDs, as well as scaffold hopping for the creation of computational libraries that could be used by regulatory bodies as support tools for scheduling procedures.<\/jats:p>","DOI":"10.1111\/cbdd.14119","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T11:41:16Z","timestamp":1657885276000},"page":"40-51","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>In silico<\/i> studies on recreational drugs: 3D quantitative structure activity relationship prediction of classified and <i>de novo<\/i> designer benzodiazepines"],"prefix":"10.1111","volume":"101","author":[{"given":"Valeria","family":"Catalani","sequence":"first","affiliation":[{"name":"Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences University of Hertfordshire  Hatfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Floresta","sequence":"additional","affiliation":[{"name":"Department of Analytical, Environmental and Forensic Sciences King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Botha","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences University of Hertfordshire  Hatfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Martin","family":"Corkery","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences University of Hertfordshire  Hatfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira","family":"Guirguis","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences University of Hertfordshire  Hatfield UK"},{"name":"Swansea University Medical School, The Grove Swansea University  Swansea UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Vento","sequence":"additional","affiliation":[{"name":"Department of Psychology Guglielmo Marconi University  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Abbate","sequence":"additional","affiliation":[{"name":"Department of Analytical, Environmental and Forensic Sciences King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Schifano","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences University of Hertfordshire  Hatfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"ACMD. 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