CD4陽性T細胞に発現するA20(tnfaip3) はTh2型アレルギー性気道炎症を抑制する

研究科: 千葉大学大学院医学薬学府（先端医学薬学専攻）学位記番号: 千大院医薬博甲第医1412号博士（医学）千葉大学 = Chiba Universit

SAR Studies of 5‑Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of <i>Toxoplasma gondii</i> CDPK1

We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from <i>T. gondii</i>. The current work, through structure–activity relationship studies, led to the discovery of compounds (<b>34</b> and <b>35</b>) with improved characteristics over the starting inhibitor <b>1</b> in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds <b>34</b> and <b>35</b> were further demonstrated to be more effective than <b>1</b> in a mouse infection model and markedly reduced the amount of <i>T. gondii</i> in the brain, spleen, and peritoneal fluid, and <b>35</b> given at 20 mg/kg eliminated <i>T. gondii</i> from the peritoneal fluid