{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:09:51Z","timestamp":1781932191841,"version":"3.54.5"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1016\/j.ejmech.2019.03.005","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T21:17:10Z","timestamp":1552079830000},"page":"112-125","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"special_numbering":"C","title":["Design, synthesis and biological evaluation of novel benzothiadiazine derivatives as potent PI3K\u03b4-selective inhibitors for treating B-cell-mediated malignancies"],"prefix":"10.1016","volume":"170","author":[{"given":"Xiaodong","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhou","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-431X","authenticated-orcid":false,"given":"Rong","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7606","key":"10.1016\/j.ejmech.2019.03.005_bib1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature17963","article-title":"Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor","volume":"534","author":"Rodrik-Outmezguine","year":"2016","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.ejmech.2019.03.005_bib2","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1021\/acs.jmedchem.5b01483","volume":"59","author":"Heffron","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"issue":"17","key":"10.1016\/j.ejmech.2019.03.005_bib3","doi-asserted-by":"crossref","first-page":"7667","DOI":"10.1021\/jm300679u","article-title":"Discovery and in\u00a0vivo evaluation of dual PI3Kbeta\/delta inhibitors","volume":"55","author":"Gonzalez-Lopez de Turiso","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2019.03.005_bib4","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1021\/acsmedchemlett.6b00438","article-title":"Discovery of a potent, selective, and orally available PI3Kdelta inhibitor for the treatment of inflammatory diseases","volume":"8","author":"Erra","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"issue":"15","key":"10.1016\/j.ejmech.2019.03.005_bib5","doi-asserted-by":"crossref","first-page":"7239","DOI":"10.1021\/acs.jmedchem.6b00799","article-title":"Evolution of a novel, orally bioavailable series of PI3Kdelta inhibitors from an inhaled lead for the treatment of respiratory disease","volume":"59","author":"Amour","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2019.03.005_bib6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrd4204","article-title":"PI3K and cancer: lessons, challenges and opportunities","volume":"13","author":"Fruman","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"issue":"Pt 6","key":"10.1016\/j.ejmech.2019.03.005_bib7","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1042\/BST0320893","article-title":"The ubiquitous phosphoinositides","volume":"32","author":"Parker","year":"2004","journal-title":"Biochem. Soc. Trans."},{"issue":"196","key":"10.1016\/j.ejmech.2019.03.005_bib8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005747","article-title":"mTORC1 inhibition is required for sensitivity to PI3K p110alpha inhibitors in PIK3CA-mutant breast cancer","volume":"5","author":"Elkabets","year":"2013","journal-title":"Sci. Transl. Med."},{"issue":"24","key":"10.1016\/j.ejmech.2019.03.005_bib9","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.2174\/09298673113209990124","article-title":"Targeting PI3K\/Akt\/mTOR cascade: the medicinal potential, updated research highlights and challenges ahead","volume":"20","author":"Ma","year":"2013","journal-title":"Curr. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2019.03.005_bib10","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1182\/blood-2011-10-386763","article-title":"PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma","volume":"119","author":"Meadows","year":"2012","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.ejmech.2019.03.005_bib11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2010-03-275305","article-title":"CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability","volume":"117","author":"Lannutti","year":"2011","journal-title":"Blood"},{"issue":"20","key":"10.1016\/j.ejmech.2019.03.005_bib12","doi-asserted-by":"crossref","first-page":"8559","DOI":"10.1021\/jm300847w","article-title":"PI3Kdelta and PI3Kgamma as targets for autoimmune and inflammatory diseases","volume":"55","author":"Cushing","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2019.03.005_bib13","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1021\/acs.jmedchem.5b01651","article-title":"Discovery, optimization, and in\u00a0vivo evaluation of benzimidazole derivatives AM-8508 and AM-9635 as potent and selective PI3Kdelta inhibitors","volume":"59","author":"Shin","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2019.03.005_bib14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.coph.2008.02.004","article-title":"Inhibition of PI-3 kinase for treating respiratory disease: good idea or bad idea?","volume":"8","author":"Thomas","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejmech.2019.03.005_bib15","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1021\/jm501629p","article-title":"Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chrom ene-6-carboxamide (AZD8186): a potent and selective inhibitor of PI3Kbeta and PI3Kdelta for the treatment of PTEN-deficient cancers","volume":"58","author":"Barlaam","year":"2015","journal-title":"J.\u00a0Med. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2019.03.005_bib16","doi-asserted-by":"crossref","first-page":"5887","DOI":"10.1021\/jm3003747","article-title":"Discovery of novel PI3-kinase delta specific inhibitors for the treatment of rheumatoid arthritis: taming CYP3A4 time-dependent inhibition","volume":"55","author":"Safina","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"issue":"17","key":"10.1016\/j.ejmech.2019.03.005_bib17","doi-asserted-by":"crossref","first-page":"7686","DOI":"10.1021\/jm300717c","article-title":"Potent and highly selective benzimidazole inhibitors of PI3-kinase delta","volume":"55","author":"Murray","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2019.03.005_bib18","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1021\/acs.jmedchem.6b01821","article-title":"Discovery of a phosphoinositide 3-kinase (PI3K) beta\/delta inhibitor for the treatment of phosphatase and tensin homolog (PTEN) deficient tumors: Building PI3Kbeta potency in a PI3Kdelta-selective template by targeting nonconserved Asp856","volume":"60","author":"Perreault","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"issue":"7","key":"10.1016\/j.ejmech.2019.03.005_bib19","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/cas.13263","article-title":"Puquitinib, a novel orally available PI3Kdelta inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia","volume":"108","author":"Xie","year":"2017","journal-title":"Cancer Sci."},{"issue":"7","key":"10.1016\/j.ejmech.2019.03.005_bib20","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1021\/acs.jmedchem.6b00213","article-title":"2,4,6-Triaminopyrimidine as a novel hinge binder in a series of PI3Kdelta selective inhibitors","volume":"59","author":"Patel","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"issue":"15","key":"10.1016\/j.ejmech.2019.03.005_bib21","doi-asserted-by":"crossref","first-page":"7252","DOI":"10.1021\/acs.jmedchem.6b00827","volume":"59","author":"Gonzalez-Lopez de Turiso","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"issue":"18","key":"10.1016\/j.ejmech.2019.03.005_bib22","doi-asserted-by":"crossref","first-page":"7381","DOI":"10.1021\/acs.jmedchem.5b00767","article-title":"Optimization of novel indazoles as highly potent and selective inhibitors of phosphoinositide 3-kinase delta for the treatment of respiratory disease","volume":"58","author":"Down","year":"2015","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.03.005_bib23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejmech.2018.03.068","article-title":"Discovery of novel quinazolinone derivatives as high potent and selective PI3Kdelta and PI3Kdelta\/gamma inhibitors","volume":"151","author":"Ma","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.03.005_bib24","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.ejmech.2016.11.014","article-title":"SAR study of 5-alkynyl substituted quinazolin-4(3H)-ones as phosphoinositide 3-kinase delta (PI3Kdelta) inhibitors","volume":"125","author":"Wei","year":"2017","journal-title":"Eur. J. Med. Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2019.03.005_bib25","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1158\/1535-7163.MCT-13-0639","article-title":"Picking the point of inhibition: a comparative review of PI3K\/AKT\/mTOR pathway inhibitors","volume":"13","author":"Dienstmann","year":"2014","journal-title":"Mol. Cancer Ther."},{"issue":"7","key":"10.1016\/j.ejmech.2019.03.005_bib26","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1158\/1078-0432.CCR-14-2034","article-title":"Idelalisib: first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma","volume":"21","author":"Yang","year":"2015","journal-title":"Clin. Cancer Res."},{"issue":"11","key":"10.1016\/j.ejmech.2019.03.005_bib27","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.chembiol.2013.09.017","article-title":"PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models","volume":"20","author":"Winkler","year":"2013","journal-title":"Chem. Biol."},{"issue":"2","key":"10.1016\/j.ejmech.2019.03.005_bib28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nchembio.293","article-title":"The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors","volume":"6","author":"Berndt","year":"2010","journal-title":"Nat. Chem. Biol."},{"issue":"13","key":"10.1016\/j.ejmech.2019.03.005_bib29","doi-asserted-by":"crossref","first-page":"8439","DOI":"10.1074\/jbc.M114.634683","article-title":"Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase delta","volume":"290","author":"Somoza","year":"2015","journal-title":"J.\u00a0Biol. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2019.03.005_bib30","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1517\/13543776.2011.629606","article-title":"Selective PI3Kdelta inhibitors, a review of the patent literature","volume":"21","author":"Norman","year":"2011","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.ejmech.2019.03.005_bib31","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jmedchem.8b01298","article-title":"Evolution of PI3K\u03b3 and \u03b4 inhibitors for inflammatory and autoimmune diseases","author":"Perry","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.03.005_bib32","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1016\/j.tet.2010.06.036","article-title":"Synthesis of isomeric fluoronitrobenzene-sulfonyl chlorides","volume":"66","author":"Zhersh","year":"2010","journal-title":"Tetrahedron"},{"issue":"11","key":"10.1016\/j.ejmech.2019.03.005_bib33","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1021\/jo00361a005","article-title":"Photoinduced ring enlargement reactions of 2H- l,2,4-benzothiadiazine 1,l-dioxides. Steady-state and laser flash photolysis studies","volume":"51","author":"Kumar","year":"1986","journal-title":"J.\u00a0Org. Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2019.03.005_bib34","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1021\/jm070694n","article-title":"Potent inhibitors of the hedgehog signaling pathway","volume":"51","author":"Brunton","year":"2008","journal-title":"J.\u00a0Med. Chem."},{"issue":"10","key":"10.1016\/j.ejmech.2019.03.005_bib35","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1021\/cb4003893","article-title":"Rutaecarpine analogues reduce lipid accumulation in adipocytes via inhibiting adipogenesis\/lipogenesis with AMPK activation and UPR suppression","volume":"8","author":"Chen","year":"2013","journal-title":"ACS Chem. Biol."},{"issue":"1","key":"10.1016\/j.ejmech.2019.03.005_bib36","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1021\/jm501624r","article-title":"Discovery and in\u00a0vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kdelta inhibitors for inflammation and autoimmune disease","volume":"58","author":"Cushing","year":"2015","journal-title":"J.\u00a0Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419302168?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419302168?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T17:49:16Z","timestamp":1559756956000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523419302168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":36,"alternative-id":["S0223523419302168"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.03.005","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and biological evaluation of novel benzothiadiazine derivatives as potent PI3K\u03b4-selective inhibitors for treating B-cell-mediated malignancies","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.03.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}