{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:20:07Z","timestamp":1774441207974,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["19ZR1454600"],"award-info":[{"award-number":["19ZR1454600"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Selective histone deacetylase 6 (HDAC6) inhibitors are safe and well\u2010tolerated with less off\u2010target effect. However, most available HDAC6 inhibitors contain hydroxamate as a zinc\u2010binding group (ZBG), and their unfavorable pharmacokinetic properties along with potential genotoxicity limited wide application in diverse diseases. Therefore, we designed and synthesized a series of selective HDAC6 inhibitors utilizing thiol as the ZBG and discussed their structure\u2010activity relationship based on molecular docking. In particular, compound <jats:bold>21<\/jats:bold>, obtained by constantly step\u2010by\u2010step simplification and evolution based on Ricolinostat, a specific HDAC6 inhibitor in Phase II, unexpectedly showed high selectivity (29\u2010fold) and moderate potency (73\u00a0nM). Utilizing pyrimidine as a linker in thiol\u2010based HDAC6 inhibitors produces an utterly novel structure, which might display different pharmacokinetic properties and genotoxicity.<\/jats:p>","DOI":"10.1111\/cbdd.14055","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T14:11:35Z","timestamp":1649686295000},"page":"90-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis and structure\u2010activity relationship of thiol\u2010based histone deacetylase 6 inhibitors"],"prefix":"10.1111","volume":"100","author":[{"given":"Zheng","family":"Guo","sequence":"first","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"Shanghai Engineering Research Center of Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"Shanghai Engineering Research Center of Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Bao","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"School of Chemistry &amp; Chemical Engineering Shanghai University of Engineering Science  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"School of Pharmacy Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu","family":"Gu","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"School of Chemistry &amp; Chemical Engineering Shanghai University of Engineering Science  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan","family":"Wang","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"Shanghai Engineering Research Center of Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianqi","family":"Li","sequence":"additional","affiliation":[{"name":"Novel Technology Center of Pharmaceutical Chemistry Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry  Shanghai China"},{"name":"Shanghai Engineering Research Center of Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021321"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4360"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5008209"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113383"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2134"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13738"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000934"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2140"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010020\u201002258\u20100"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718823114"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.8b00487"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.5b00303"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201500486"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112887"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.08.016"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(16)30375\u20108"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01782"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.14055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T12:20:03Z","timestamp":1692879603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/cbdd.14055"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14055","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"assertion":[{"value":"2021-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}