{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:20:02Z","timestamp":1760314802065,"version":"build-2065373602"},"reference-count":53,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007065","name":"Universit\u00e0 degli Studi di Salerno","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["095751\/Z\/11\/Z"],"award-info":[{"award-number":["095751\/Z\/11\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N010051\/1"],"award-info":[{"award-number":["MR\/N010051\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000192","name":"Ontario Ministry of Economic Development and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000192","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092809\/Z\/10\/Z"],"award-info":[{"award-number":["092809\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/J001201\/2"],"award-info":[{"award-number":["BB\/J001201\/2"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2022,10,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The bromodomain and extra\u2010terminal (BET) family of proteins includes BRD2, BRD3, BRD4, and the testis\u2010specific protein, BRDT, each containing two <jats:italic>N<\/jats:italic>\u2010terminal tandem bromodomain (BRD) modules. Potent and selective inhibitors targeting the two bromodomains are required to elucidate their biological role(s), with potential clinical applications. In this study, we designed and synthesized a series of benzimidazole\u20106\u2010sulfonamides starting from the azobenzene compounds MS436 (<jats:bold>7\u2009a<\/jats:bold>) and MS611 (<jats:bold>7\u2009b<\/jats:bold>) that exhibited preference for the first (BD1) over the second (BD2) BRD of BET family members. The most\u2010promising compound (<jats:bold>9\u2009a)<\/jats:bold> showed good binding potency and improved metabolic stability and selectivity towards BD1 with respect to the parent compounds.<\/jats:p>","DOI":"10.1002\/cmdc.202200343","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T08:12:23Z","timestamp":1661847143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Discovery of Benzo[<i>d<\/i>]imidazole\u20106\u2010sulfonamides as Bromodomain and Extra\u2010Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-5914","authenticated-orcid":false,"given":"Alessandra","family":"Cipriano","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-1376","authenticated-orcid":false,"given":"Ciro","family":"Milite","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-7858","authenticated-orcid":false,"given":"Alessandra","family":"Feoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-790X","authenticated-orcid":false,"given":"Monica","family":"Viviano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-2023","authenticated-orcid":false,"given":"Giacomo","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-2181","authenticated-orcid":false,"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3136-0469","authenticated-orcid":false,"given":"Giuliana","family":"Sarno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-4455","authenticated-orcid":false,"given":"Sarah","family":"Picaud","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Oxford University  OX3 7DQ Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-4693","authenticated-orcid":false,"given":"Satomi","family":"Imaide","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery School of Life Sciences University of Dundee  Dow Street Dundee DD1 5EH, Scotland UK"},{"name":"Discovery Technology Research Laboratories Ono Pharmaceutical Co., Ltd.  618-8585 Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-0748","authenticated-orcid":false,"given":"Nikolai","family":"Makukhin","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery School of Life Sciences University of Dundee  Dow Street Dundee DD1 5EH, Scotland UK"},{"name":"Oncology R&amp;D Tumour Targeted Delivery AstraZeneca QMB Innovation Centre  42 New Road London E1 2AX UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-1317","authenticated-orcid":false,"given":"Panagis","family":"Filippakopoulos","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Oxford University  OX3 7DQ Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-1670","authenticated-orcid":false,"given":"Alessio","family":"Ciulli","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Drug Discovery School of Life Sciences University of Dundee  Dow Street Dundee DD1 5EH, Scotland UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-3704","authenticated-orcid":false,"given":"Sabrina","family":"Castellano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0748-1145","authenticated-orcid":false,"given":"Gianluca","family":"Sbardella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  via Giovanni Paolo II 132 84084 Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.143"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3256"},{"key":"e_1_2_8_3_1","unstructured":"\u00a0"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09504"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09589"},{"key":"e_1_2_8_6_1","unstructured":"\u00a0"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2020.05.006"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01761"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01487"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01321-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0030-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz8455"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01835"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2005.10.014"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.05.009"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01010"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00614"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401334s"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13571"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166022"},{"key":"e_1_2_8_22_1","unstructured":"\u00a0"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b02008"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm5019687"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12462"},{"key":"e_1_2_8_26_1","unstructured":"\u00a0"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja412434f"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01670"},{"key":"e_1_2_8_29_1","unstructured":"\u00a0"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.11.020"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113953"},{"key":"e_1_2_8_32_1","unstructured":"\u00a0"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.10.080"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC05054J"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09504"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/9781118180778.app1","volume-title":"ADME-Enabling Technologies in Drug Design and Development","author":"Zhang D.","year":"2012"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-742-6_7"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100762r"},{"key":"e_1_2_8_39_1","unstructured":"\u00a0"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm970530e"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.03.039"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250903042318"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00412"},{"key":"e_1_2_8_44_1","unstructured":"\u00a0"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00746"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01666"},{"key":"e_1_2_8_47_1","unstructured":"\u00a0"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.017"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1108190108"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2019.1666836"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm001020e"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/108705710100600309"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(89)90213-3"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202200343","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202200343","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202200343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:27:21Z","timestamp":1760257641000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202200343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":53,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2022,10,19]]}},"alternative-id":["10.1002\/cmdc.202200343"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202200343","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"type":"print","value":"1860-7179"},{"type":"electronic","value":"1860-7187"}],"subject":[],"published":{"date-parts":[[2022,9,15]]},"assertion":[{"value":"2022-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202200343"}}