{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T15:58:18Z","timestamp":1757779098756},"reference-count":13,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2001,9,1]],"date-time":"2001-09-01T00:00:00Z","timestamp":999302400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2001,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC\n            <jats:sub>90<\/jats:sub>\n            s) for the four test compounds for strains of\n            <jats:italic>Candida<\/jats:italic>\n            spp. ranged from &lt;0.048 to 0.78 \u03bcg\/ml. All compounds were also active against FLC-resistant\n            <jats:italic>Candida albicans<\/jats:italic>\n            and other\n            <jats:italic>Candida<\/jats:italic>\n            sp. strains. Moreover, MIC\n            <jats:sub>90<\/jats:sub>\n            s for strains of\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            ,\n            <jats:italic>Aspergillus<\/jats:italic>\n            spp.,\n            <jats:italic>Trichophyton<\/jats:italic>\n            spp., and\n            <jats:italic>Microsporum<\/jats:italic>\n            spp. were also low and ranged from &lt;0.048 to 0.39 \u03bcg\/ml. The test compounds produced a fungistatic pattern during the time-kill kinetic studies. In vivo studies indicated that all four test compounds have good efficacies against\n            <jats:italic>C. albicans<\/jats:italic>\n            in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against an\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.\n          <\/jats:p>","DOI":"10.1128\/aac.45.9.2420-2426.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"2420-2426","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro and In Vivo Activities of Syn2836, Syn2869, Syn2903, and Syn2921: New Series of Triazole Antifungal Agents"],"prefix":"10.1128","volume":"45","author":[{"given":"S. M.","family":"Salama","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Atwal","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Simon","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Poglod","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Montaseri","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. K.","family":"Khan","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Furukawa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Saito","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Nishida","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Higashitani","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Uji","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Unemi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Taiho Pharmaceutical Company, 224-2, Ebisuno, Hiraishi, Kawauchi-Cho, Tokushima 771-01, Japan2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Daneshtalab","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. G.","family":"Micetich","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->NAEJA Pharmaceutical, Inc., Edmonton, Alberta, Canada T6E 5V2,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0002-9343(94)90023-X","article-title":"NIAID Mycoses Study Group multicentre trial of oral itraconazole therapy for invasive aspergillosis.","volume":"97","author":"Denning D. W.","year":"1994","unstructured":"Denning D. W. Lee J. Y. Hostetler J. S. Pappas P. Kauffman C. A. Dewsnup D. H. Glagiani J. N. Graybill J. R. Sugar A. M. Catanzaro A. Gallis H. Perfect J. R. Dockery B. Dismukes W. E. Stevens D. A. NIAID Mycoses Study Group multicentre trial of oral itraconazole therapy for invasive aspergillosis. Am. J. Med. 97 1994 135 144","journal-title":"Am. J. 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