{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T12:02:30Z","timestamp":1778328150368,"version":"3.51.4"},"reference-count":54,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2018,6]]},"DOI":"10.1016\/j.bmcl.2018.03.020","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T21:15:44Z","timestamp":1520543744000},"page":"1972-1980","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"title":["Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability"],"prefix":"10.1016","volume":"28","author":[{"given":"Jeffery D.","family":"Zwicker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas A.","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo J.","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul D.","family":"Kirchhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duxin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vern B.","family":"Carruthers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2018.03.020_b0005","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4103\/0974-777X.83536","article-title":"Toxoplasmosis: a global threat","volume":"3","author":"Furtado","year":"2011","journal-title":"J Glob Infect Dis"},{"key":"10.1016\/j.bmcl.2018.03.020_b0010","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1086\/590149","article-title":"Management of toxoplasma gondii infection during pregnancy","volume":"47","author":"Montoya","year":"2008","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.bmcl.2018.03.020_b0015","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3201\/eid1701.P11101","article-title":"Foodborne illness acquired in the United States\u2013major pathogens","volume":"17","author":"Scallan","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"10.1016\/j.bmcl.2018.03.020_b0020","doi-asserted-by":"crossref","first-page":"794","DOI":"10.4269\/ajtmh.13-0722","article-title":"Neglected parasitic infections in the United States: toxoplasmosis","volume":"90","author":"Jones","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"10.1016\/j.bmcl.2018.03.020_b0025","doi-asserted-by":"crossref","first-page":"783","DOI":"10.4269\/ajtmh.13-0727","article-title":"Neglected parasitic infections in the United States: needs and opportunities","volume":"90","author":"Parise","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"10.1016\/j.bmcl.2018.03.020_b0030","doi-asserted-by":"crossref","first-page":"e1006351","DOI":"10.1371\/journal.ppat.1006351","article-title":"Toxoplasma gondii: entry, association, and physiological influence on the central nervous system","volume":"13","author":"Mendez","year":"2017","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.bmcl.2018.03.020_b0035","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.pt.2017.04.001","article-title":"Brains and brawn: toxoplasma infections of the central nervous system and skeletal muscle","volume":"33","author":"Wohlfert","year":"2017","journal-title":"Trends Parasitol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0040","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1586\/14787210.2015.1051033","article-title":"Schizophrenia and toxoplasma gondii: an undervalued association?","volume":"13","author":"Flegr","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"key":"10.1016\/j.bmcl.2018.03.020_b0045","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/acps.12423","article-title":"Beyond the association. toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis","volume":"132","author":"Sutterland","year":"2015","journal-title":"Acta Psychiatr Scand"},{"key":"10.1016\/j.bmcl.2018.03.020_b0050","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pt.2013.01.007","article-title":"How and why toxoplasma makes us crazy","volume":"29","author":"Flegr","year":"2013","journal-title":"Trends Parasitol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0055","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/0020-7519(95)00067-C","article-title":"A ubiquitous intracellular parasite: the cellular biology of Toxoplasma gondii","volume":"25","author":"Smith","year":"1995","journal-title":"Int J Parasitol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0060","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1007\/s00436-017-5478-y","article-title":"Toxoplasma gondii and schizophrenia: a review of published RCTs","volume":"116","author":"Chorlton","year":"2017","journal-title":"Parasitol Res"},{"key":"10.1016\/j.bmcl.2018.03.020_b0065","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3109\/00365548.2012.693197","article-title":"A review on human toxoplasmosis","volume":"44","author":"Saadatnia","year":"2012","journal-title":"Scand J Infect Dis"},{"key":"10.1016\/j.bmcl.2018.03.020_b0070","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13071-015-0902-6","article-title":"Diagnosis of toxoplasmosis and typing of toxoplasma gondii","volume":"8","author":"Liu","year":"2015","journal-title":"Parasites Vectors"},{"key":"10.1016\/j.bmcl.2018.03.020_b0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(01)00438-8","article-title":"Cysteine proteases of parasitic organisms","volume":"120","author":"Sajid","year":"2002","journal-title":"Mol Biochem Parasitol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0080","doi-asserted-by":"crossref","first-page":"e1023","DOI":"10.1371\/journal.pntd.0001023","article-title":"Mining a cathepsin inhibitor library for new antiparasitic drug leads","volume":"5","author":"Ang","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"10.1016\/j.bmcl.2018.03.020_b0085","doi-asserted-by":"crossref","first-page":"7444","DOI":"10.1016\/j.bmcl.2010.10.015","article-title":"Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease","volume":"20","author":"Beaulieu","year":"2010","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0090","doi-asserted-by":"crossref","first-page":"26839","DOI":"10.1074\/jbc.M109.003780","article-title":"Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl","volume":"284","author":"Larson","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0095","doi-asserted-by":"crossref","first-page":"17096","DOI":"10.1038\/nmicrobiol.2017.96","article-title":"Toxoplasma depends on lysosomal consumption of autophagosomes for persistent infection","volume":"2","author":"Di Cristina","year":"2017","journal-title":"Nat Microbiol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0100","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.pain.2006.11.017","article-title":"Role of the cysteine protease cathepsin S in neuropathic hyperalgesia","volume":"130","author":"Barclay","year":"2007","journal-title":"Pain"},{"key":"10.1016\/j.bmcl.2018.03.020_b0105","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2174\/1389557033488079","article-title":"Non-peptidic inhibitors of cysteine proteases","volume":"3","author":"Schirmeister","year":"2003","journal-title":"Mini Rev Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0110","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine cathepsins: from structure, function and regulation to new frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.bmcl.2018.03.020_b0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18388\/abp.2001_5108","article-title":"Structural studies of cysteine proteases and their inhibitors","volume":"48","author":"Grzonka","year":"2001","journal-title":"Acta Biochim Pol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0120","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/15216540500154920","article-title":"Lysosomal cysteine proteases: structural features and their role in apoptosis","volume":"57","author":"Stoka","year":"2005","journal-title":"IUBMB Life"},{"key":"10.1016\/j.bmcl.2018.03.020_b0125","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.lfs.2009.11.016","article-title":"Cathepsin L, target in cancer treatment?","volume":"86","author":"Lankelma","year":"2010","journal-title":"Life Sci"},{"key":"10.1016\/j.bmcl.2018.03.020_b0130","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biophys.28.1.181","article-title":"The lysosomal cysteine proteases","volume":"28","author":"McGrath","year":"1999","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"10.1016\/j.bmcl.2018.03.020_b0135","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1006\/bbrc.1999.1830","article-title":"Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain-CLIK148 complex","volume":"266","author":"Tsuge","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.bmcl.2018.03.020_b0140","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.apsb.2015.08.001","article-title":"Cysteine proteases as therapeutic targets: does selectivity matter? a systematic review of calpain and cathepsin inhibitors","volume":"5","author":"Siklos","year":"2015","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.bmcl.2018.03.020_b0145","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijpddr.2014.02.002","article-title":"Drug repurposing and human parasitic protozoan diseases","volume":"4","author":"Andrews","year":"2014","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"10.1016\/j.bmcl.2018.03.020_b0150","unstructured":"Inc. CCG. Molecular Operating Environment (MOE), 2013.08 2015."},{"key":"10.1016\/j.bmcl.2018.03.020_b0155","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1016\/j.bmcl.2009.05.071","article-title":"Dipeptidyl nitrile inhibitors of Cathepsin L","volume":"19","author":"Asaad","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0160","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2174\/156802610790725452","article-title":"Development of nitrile-based peptidic inhibitors of cysteine cathepsins","volume":"10","author":"Frizler","year":"2010","journal-title":"Curr Top Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0165","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/cmdc.201500151","article-title":"Active site mapping of human cathepsin f with dipeptide nitrile inhibitors","volume":"10","author":"Schmitz","year":"2015","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0170","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/jm101272p","article-title":"Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors","volume":"54","author":"Frizler","year":"2011","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0175","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1021\/cr010182v","article-title":"Irreversible inhibitors of serine, cysteine, and threonine proteases","volume":"102","author":"Powers","year":"2002","journal-title":"Chem Rev"},{"key":"10.1016\/j.bmcl.2018.03.020_b0180","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2174\/156802606776287081","article-title":"Inhibitors of cysteine proteases","volume":"6","author":"Vicik","year":"2006","journal-title":"Curr Top Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0185","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.apsb.2015.08.001","article-title":"Cysteine proteases as therapeutic targets: does selectivity matter? a systematic review of calpain and cathepsin inhibitors","volume":"5","author":"Siklos","year":"2015","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.bmcl.2018.03.020_b0190","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.1021\/acs.jmedchem.5b00746","article-title":"Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as potent cathepsin K inhibitors","volume":"58","author":"Borisek","year":"2015","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0195","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/anie.201006781","article-title":"Systematic investigation of halogen bonding in protein-ligand interactions","volume":"50","author":"Hardegger","year":"2011","journal-title":"Angew Chem Int Ed Engl"},{"key":"10.1016\/j.bmcl.2018.03.020_b0200","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nsb0297-105","article-title":"Crystal structure of human cathepsin K complexed with a potent inhibitor","volume":"4","author":"McGrath","year":"1997","journal-title":"Nat Struct Biol"},{"key":"10.1016\/j.bmcl.2018.03.020_b0205","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1021\/jm010206q","article-title":"Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design","volume":"44","author":"Greenspan","year":"2001","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0210","article-title":"Engineering the S2 Subsite Specificity of Human Cathepsin-S to a Cathepsin-L-Like and Cathepsin-B-Like Specificity","volume":"152\u2013152","author":"Bromme","year":"1994","journal-title":"J Cell Biochem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0215","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1016\/j.bmcl.2005.07.071","article-title":"Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K","volume":"15","author":"Black","year":"2005","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0220","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bmcl.2007.12.047","article-title":"The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K","volume":"18","author":"Gauthier","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0225","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1021\/jo8020314","article-title":"A practical enantioselective synthesis of odanacatib, a potent cathepsin k inhibitor, via triflate displacement of an alpha-trifluoromethylbenzyl triflate","volume":"74","author":"O'Shea","year":"2009","journal-title":"J Org Chem"},{"key":"10.1016\/j.bmcl.2018.03.020_b0230","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1055\/s-2005-868494","article-title":"Practical and efficient route to (S)-gamma-fluoroleucine","volume":"8","author":"Truong","year":"2005","journal-title":"Synlett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0235","unstructured":"Humphrey G, Chung CK, Rivera NR, Belyk KM. Asymmetric synthesis for preparing fluoroleucine alkyl esters. Google Patents; 2013."},{"key":"10.1016\/j.bmcl.2018.03.020_b0240","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1055\/s-0035-1561568","article-title":"Expedient Synthesis of Fmoc-(S)\u2013Fluoroleucine and Late-Stage Fluorination of Peptides","volume":"27","author":"Fanelli","year":"2016","journal-title":"Synlett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0245","doi-asserted-by":"crossref","unstructured":"Smith HJ, Simons C. Proteinase and peptidase inhibition: recent potential targets for drug development. London; New York: Taylor & Francis; 2002.","DOI":"10.1201\/b12653"},{"key":"10.1016\/j.bmcl.2018.03.020_b0250","unstructured":"Bryant CM, Bunin BA, Kraynack EA, Patterson JW. N-cyanomethyl amides as protease inhibitors; 2001."},{"key":"10.1016\/j.bmcl.2018.03.020_b0255","first-page":"42","article-title":"The trifluoroethylamine function as peptide bond replacement","volume":"24","author":"Sani","year":"2006","journal-title":"Chim Oggi"},{"key":"10.1016\/j.bmcl.2018.03.020_b0260","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1016\/j.bmcl.2007.06.023","article-title":"The identification of potent, selective, and bioavailable cathepsin S inhibitors","volume":"17","author":"Gauthier","year":"2007","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0265","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1021\/ml100016x","article-title":"SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism","volume":"1","author":"Rydberg","year":"2010","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2018.03.020_b0270","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.1021\/acs.orglett.7b01880","article-title":"Introduction of Trifluoroethylamine as Amide Isostere by C-H Functionalization of Heteroarenes","volume":"19","author":"Braun","year":"2017","journal-title":"Org Lett"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X18301999?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X18301999?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:26:10Z","timestamp":1760772370000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X18301999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":54,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["S0960894X18301999"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2018.03.020","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2018.03.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}