{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T03:13:19Z","timestamp":1787109199270,"version":"build-2736575974"},"reference-count":84,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T00:00:00Z","timestamp":1175212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2007,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polychlorinated dibenzo\u2010p\u2010dioxins are persistent environmental pollutants. The most potent congener, 2,3,7,8\u2010tetrachlorodibenzo\u2010p\u2010dioxin (TCDD), causes a wasting syndrome and is a potent carcinogen and immunosuppressant in the rat at high doses. However, low doses cause opposite effects to some of those observed at higher doses, resulting in chemoprevention, stimulation of the immune system, and longevity in experimental animals. The new TCDD analogue, 2,3,7,8\u2010tetrachlorophenothiazine (TCPT), was developed to take advantage of the low\u2010dose effects of dioxins that have potential application as therapeutics. Its development marked a deviation from the traditional scope of phenothiazine drug design by deriving biological effects from aryl substituents. TCPT was synthesized in three steps. The key ring\u2010closing step was performed utilizing a Buchwald\u2010Hartwig amination to provide TCPT in 37\u2009% yield. Its potency to induce CYP1A1 activity over 24\u2005h was 370 times lower than that of TCDD in\u2005vitro. The elimination half\u2010life of the parent compound in serum was 5.4\u2005h in the rat and 2.7\u2005h in the guinea pig, compared to 11 and 30 days, respectively, for TCDD. These initial findings clearly differentiate TCPT from TCDD and provide the basis for further studies of its potential as a drug lead.<\/jats:p>","DOI":"10.1002\/cmdc.200700005","type":"journal-article","created":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T05:15:19Z","timestamp":1175231719000},"page":"890-897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["From Dioxin to Drug Lead\u2014The Development of 2,3,7,8\u2010Tetrachlorophenothiazine"],"prefix":"10.1002","volume":"2","author":[{"given":"Kristian\u2005W.","family":"Fried","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher\u2005M.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Werner","family":"Schramm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurba","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naima","family":"Chahbane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Corsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas\u2005R.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Lenoir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius","family":"Kettrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Terranova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunda\u2005I.","family":"Georg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2005K.","family":"Rozman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,31]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0045-6535(99)00358-6"},{"key":"e_1_2_6_2_2","unstructured":"NATO North Atlantic Treaty Organization Br\u00fcssel 1988."},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7305101"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(84)90357-0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(78)90075-3"},{"key":"e_1_2_6_6_2","first-page":"333","volume":"45","author":"Sharma R. P.","year":"1978","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408449309105013"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi106"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(83)90123-0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(84)90322-3"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1289\/ehp.7305125","volume":"5","author":"Gupta B. N.","year":"1973","journal-title":"Environ. Health Perspect."},{"key":"e_1_2_6_12_2","first-page":"145","volume":"27","author":"Poland A.","year":"1978","journal-title":"Ecol. Bull."},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0015-6264(71)90045-9"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.856141"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.22.040182.002505"},{"key":"e_1_2_6_16_2","first-page":"333","volume-title":"Biologic mechanisms of dioxin action, Vol. Banbury Report 18","author":"Thunberg T.","year":"1984"},{"key":"e_1_2_6_17_2","first-page":"81","volume":"37","author":"Rozman K.","year":"1989","journal-title":"Dermatol. Beruf Umwelt"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0940-2993(11)80160-0"},{"key":"e_1_2_6_19_2","first-page":"108","author":"Schulz H.","year":"1887","journal-title":"Arch. Pathol. Anat. Physiol. Klin. Med."},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/713611037"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2005.01.013"},{"key":"e_1_2_6_22_2","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-662-33987-9","volume-title":"Zur Geschichte des Gaskrieges. F\u00fcnf Vortr\u00e4ge aus den Jahren 1920\u20131923","author":"Haber F.","year":"1924"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(00)00230-4"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(00)00447-9"},{"key":"e_1_2_6_25_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S0022-3565(24)38800-7","volume":"296","author":"Rozman K. K.","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.06.009"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(95)03252-G"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1157"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1511\/2003.38.904"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/15401420391434298"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(87)90031-X"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0045-6535(02)00030-9"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(90)90081-Q"},{"key":"e_1_2_6_34_2","volume-title":"Goodman & Gilman's The Pharmacological Basis of Therapeutics 10th Edition","year":"2001"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1991.tb01421.x"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420100212"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(76)90601-3"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(77)90029-1"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1960.03590120014002"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570240111"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(77)90340-9"},{"key":"e_1_2_6_42_2","first-page":"255","volume":"19","author":"Lullmann\u2010Rauch R.","year":"1975","journal-title":"Virchows Arch. B"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.08.061"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(69)90178-6"},{"key":"e_1_2_6_45_2","first-page":"49","volume-title":"Biological mechanisms of dioxin action, Vol.\u200518","author":"Neal R.","year":"1984"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0567740872003644"},{"key":"e_1_2_6_47_2","first-page":"311","volume":"2","author":"Senma M.","year":"1973","journal-title":"Cryst. Struct. Commun."},{"key":"e_1_2_6_48_2","unstructured":"K.\u2005W. Fried Masters thesis Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen Germany 2000."},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.43.100901.135828"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(02)00063-7"},{"key":"e_1_2_6_51_2","first-page":"66","volume":"3","author":"Li D.\u2010X.","year":"1988","journal-title":"J. Shivaji Univ."},{"key":"e_1_2_6_52_2","first-page":"112","volume":"17","author":"Huang S.","year":"1997","journal-title":"Guangpuxue Yu Guangpu Fenxi"},{"key":"e_1_2_6_53_2","unstructured":"K.\u2005W. Fried Doctoral Dissertation thesis Technische Universit\u00e4t M\u00fcnchen Germany 2004."},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2725(08)60375-X"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.3987\/R-1987-01-0239"},{"key":"e_1_2_6_56_2","first-page":"186","volume":"3","author":"B\u00e9champ A. J.","year":"1854","journal-title":"Ann. Chim. Phys."},{"key":"e_1_2_6_57_2","first-page":"401","volume":"93","author":"B\u00e9champ A. J.","year":"1854","journal-title":"Justus Liebigs Ann. Chem."},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570040425"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(03)00898-0"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2004.09.071"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo991699y"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3757(19980803)110:15<2154::AID-ANGE2154>3.0.CO;2-C"},{"key":"e_1_2_6_62_3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19980817)37:15<2046::AID-ANIE2046>3.0.CO;2-L"},{"key":"e_1_2_6_63_2","first-page":"1822","volume":"12","author":"Maes B. U. W.","year":"2003","journal-title":"Synth. Lett."},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja992130h"},{"key":"e_1_2_6_65_2","first-page":"1","volume-title":"General Principles of Toxicology","author":"Rozman K. K.","year":"1998"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20365"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2004.tb03162.x"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400004200"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(96)00522-9"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91130-I"},{"key":"e_1_2_6_71_2","first-page":"385","volume":"14","author":"Kerecsen L.","year":"1994","journal-title":"Toxicologist"},{"key":"e_1_2_6_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1972.tb08889.x"},{"key":"e_1_2_6_73_2","unstructured":"K.\u2005K.Rozman K.\u2005W.Fried P.\u2005F.Terranova G.\u2005I.Georg A.Dutta United States Patent Application 10\/875 864 2005; PCT Patent Application PCT\/US05\/0251312005."},{"key":"e_1_2_6_74_2","first-page":"229","volume":"13","author":"Pitot H. C.","year":"1964","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"e_1_2_6_75_2","first-page":"891","volume":"26","author":"Reuber M. D.","year":"1961","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_2_6_76_2","volume-title":"Arbeitsanweisung\/SOP Micro\u2010EROD\u2010Assay (in\u2005vitro)","author":"Doods K.","year":"2003"},{"key":"e_1_2_6_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01409106"},{"key":"e_1_2_6_78_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1381"},{"key":"e_1_2_6_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-9936(98)00102-2"},{"key":"e_1_2_6_80_2","first-page":"554","volume":"14","author":"Majors R. E.","year":"1996","journal-title":"LC\u2010GC"},{"key":"e_1_2_6_81_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00323048"},{"key":"e_1_2_6_82_2","first-page":"602","volume":"15","author":"Boos K.\u2010S.","year":"1997","journal-title":"LC\u2010GC"},{"key":"e_1_2_6_83_2","first-page":"814","volume":"15","author":"Rudolphi A.","year":"1997","journal-title":"LC\u2010GC"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.200700005","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.200700005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T15:30:58Z","timestamp":1760283058000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.200700005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,31]]},"references-count":84,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,6,11]]}},"alternative-id":["10.1002\/cmdc.200700005"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.200700005","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,31]]},"assertion":[{"value":"2007-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}