JP4493337B2 - 3−β−D−リボフラノシルチアゾロ[4,5−d]ピリミジンヌクレオシド及びその使用 - Google Patents
3−β−D−リボフラノシルチアゾロ[4,5−d]ピリミジンヌクレオシド及びその使用 Download PDFInfo
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- 0 *c(nc(N)nc1N2[C@@]([C@@]3O)O[C@](CO)C3O)c1SC2=O Chemical compound *c(nc(N)nc1N2[C@@]([C@@]3O)O[C@](CO)C3O)c1SC2=O 0.000 description 3
- JZZRSSNUBIIJRU-IFXMLGAMSA-N CC(C)(C)[C@@H](C(OC[C@H]([C@H]([C@H]1O)O)O[C@H]1N(c1nc(N)nc(O)c1S1)C1=O)=O)N Chemical compound CC(C)(C)[C@@H](C(OC[C@H]([C@H]([C@H]1O)O)O[C@H]1N(c1nc(N)nc(O)c1S1)C1=O)=O)N JZZRSSNUBIIJRU-IFXMLGAMSA-N 0.000 description 1
- KYCFCJJNZAMKHW-FWROPDTPSA-N CCC(C)[C@@H](C(OC[C@H]([C@H]([C@H]1O)O)O[C@H]1N(c1nc(N)nc(O)c1S1)C1=O)=O)N Chemical compound CCC(C)[C@@H](C(OC[C@H]([C@H]([C@H]1O)O)O[C@H]1N(c1nc(N)nc(O)c1S1)C1=O)=O)N KYCFCJJNZAMKHW-FWROPDTPSA-N 0.000 description 1
- BBLQSWGGUCEGTH-ZIYNGMLESA-N Nc(nc1N2[C@@H]([C@@H]3O)O[C@H](CO)[C@H]3O)ncc1SC2=O Chemical compound Nc(nc1N2[C@@H]([C@@H]3O)O[C@H](CO)[C@H]3O)ncc1SC2=O BBLQSWGGUCEGTH-ZIYNGMLESA-N 0.000 description 1
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Description
R2はH、OR5又はN(R6)2であり、このうちR5は独立にH又はアルキル基であり、R6は独立にH、又は、置換若しくは無置換のアルキル基、シクロアルキル基若しくは窒素と共に置換又は無置換のヘテロシクロアルキル環を形成している;R2が−OHである場合、少なくとも一つのR1基はラセミ、L−又はD−体の−C(O)CHNH2R4である]。
本発明において以下の用語が使用されているところでは、その用語は以下に定義するように使用されている。
(i)疾患、異常及び/又は病的状態に対する素因があるかも知れないが、まだ疾患、異常又は病的状態であるとは診断されていない動物において、疾患、異常及び/又は病的状態にならないように防止すること
(ii)疾患、異常又は病的状態を抑制すること、すなわちその発生を阻止すること
(iii)疾患、異常又は病的状態を軽減すること、すなわち疾患、異常又は病的状態の退縮を起こさせること
をいう。
粉末又は顆粒等の流動可能な形状の活性成分と、必要に応じて結合剤、潤滑剤、不活性な希釈剤、表面活性剤又は分散剤を混合して、適当な機械で打錠することにより作ることができる。成形錠剤は、粉末の活性成分と不活性な液体希釈剤で湿らせた適当な担体の混合物を、適当な機械にて成形することにより作ることができる。
下記に述べる合成スキームにおいては、特に示していない限り全ての温度は摂氏(℃)で示し、全ての部及び百分率は重量により示してある。試薬はアルドリッチ・ケミカル・カンパニーやランカスター・シンセシス・リミテッド等の市販品提供業者から購入し、特に示していない限り更に精製することなく使用した。テトラヒドロフラン(THF)及びN,N−ジメチルホルムアミド(DMF)はアルドリッチから密封瓶(シュア・シール・ボトル)で購入し、そのまま使用した。特に示していない限り、以下の溶媒及び試薬は、乾燥窒素雰囲気下で蒸留した。THF及びEt2OはNa−ベンゾフェノン=ケチルから蒸留した。CH2Cl2、ジイソプロピルアミン、ピリジン及びEt3NはCaH2から蒸留した。MeCNはまずP2O5から蒸留し、次にCaH2から蒸留した。MeOHはMgから蒸留した。PhMe、EtOAc及びi−PrOAcはCaH2から蒸留した。TFAAは乾燥アルゴン下で単純に大気圧蒸留することにより精製した。
s(シングレット:一重項)、d(ダブレット:二重項)、t(トリプレット:三重項)、q(カルテット:四重項)、m(マルチプレット:多重項)、br(ブロードなピーク)、dd(ダブル・ダブレット)、dt(ダブル・トリプレット)。カップリング定数が示されている場合はヘルツ(Hz)で報告している。
融点280〜281℃、1H(DMSO−d6)δ1.28(s,3H),1.47(s,3H),3.43−3.55(m,2H),3.95−3.99(m, 1H),4.77−4. 80(m,1H),4.88−4.91(m,1H),5.24−5.26(m,1H),5.99(s,1H),6.97(br s,2H),11.25(s,1H).
融点158℃(分解(dec));1H(CDC13)δ0.86(d,J=7.0,3H), 0.95(d,J=7.0,3H),1.35(s,3H),1.44(s,9H),1.56(s,3H),1.75(br s,1H),2.08−2.19(m,1H),4.20−4.24(m,2H),4.30−4.37(m,1H),4.56(dd,J=11.0,5.9,1H),4.96(dd,J=6.2,3.7,1H),5.11(br d,J=8.8,1H),5.29(br d,J=6.6,1H),5.88(br s,2H),6.23(s, 1H).
融点166−68℃(分解(dec));1H(DMSO−d6)δ0.90(d,J=7.0,3H),0.94(d,J=7.0,3H),2.14−2.18(m,1H),3.83−3.85(m,1H),3.96−4.00(m,1H),4.23−4.28(m,2H),4.42(dd,J=11.7,3.4,1H),4.75(dd,J=10.3,5.5,1H),5.81(br d,J=4.4,1H),6.46(br s,3H),7.23(br s,2H),8.47(s, 3H),11.5(br s,1H).
C15H21N5O7S・2HClに対する元素分析:計算値:C,36.89;H,4.75;Cl,14.52;N,14.34;S,6.57;実測値:C,37.03;H,4.74;Cl,14.26;N,14.24;S,6.42.
1H NMR(400MHz,d6−DMSO)δ11.29(s,1H),7.09(d, J=8.0,1H),7.02(br s,1H),6.02(s,1H),5.28(d, J=6.2,1H),5.06(br s,1H),4.16−4.22(m,2H),3.85(dd,J=8.0,6.6,1H),1.68(br s,1H),1.47(s,3H),1.34(s,9H),1.29(s,3H),0.71−0.89(m,5H).
融点173−174℃(分解(dec));1H NMR(400MHz,d6−DMSO) δ11.41(br s,1H),8.41(br s,3H),7.15(br s,2H), 5.82(d,J=4.8,1H),4.50−5.00(m,2H),4.40(dd, J=11.7,3.3,1H),4.21−4.30(m,2H),3.91−4.0(m, 2H),1.84−1.91(m,1H),1.37−1.44(m,1H),1.19−1.27(m,1H),0.80−0.87(m,6H).
C16H23N5O7S・3/2HClに対する元素分析:計算値:C,39.69;H,5.10;N,14.47;Cl,10.98;S,6.62;実測値:C,39.05;H,5.13;N,13.73;Cl,11.08;S,6.02.
1H NMR(400MHz,d6−DMSO)δ11.28(br s,1H),6.70−7.40(m,3H),6.02(s,1H),5.30(d,J=6.2,1H),5.05(br s,1H),4.17−4.24(m,3H),3.77(d,J=8.4,1H),1.47(s,3H),1.33(s,9H),1.29(s,3H),0.85(s,9H).
融点202−203℃(分解(dec));1H NMR(400MHz,d6−DMSO) δ11.35(br s,1H),8.31(br s,3H),7.08(br s,2H),5.83(d,J=4.0,1H),5.45(br s,1H),5.21(br s,1H),4.77−4.82(m,1H),4.42(dd,J=11.4,2.6,1H),4.23−4.28(m,1H),3.96−4.04(m,1H),3.74(s,1H),0.97(s,9H).
C16H23N5O7S・HClに対する元素分析:計算値:C,41.25;H,5.19;N,15.03;Cl,7.61;S,6.88; 実測値:C,40.41;H,5.41;N,14.16;Cl,7.01;S,6.23.
1H NMR(400MHz,d6−DMSO) 回転異性体のカルバメート δ11.28(br s,1H),7.00(br s,2H),6.02(s,1H),5.27(d, J=6.6,1H),5.04(br s,1H),4.14−4.28(m,3H),3.91(d,J=9.5,1H),2.79(br s,3H),2.09(br s,1H),1.46(s,3H),1.36(s,4.5H),1.32(s,4.5H),1.28(s,3H),0.78−0.89(m,6H).
融点>180℃(分解(dec);1H NMR(400MHz,d6−DMSO)δ11.31(br s,1H),9.05(br s,2H),7.05(br s,2H),5.83(d,J=4.4,1H),5.46(br s,1H),5.21(br s,1H), 4.76−4.82(m,1H),4.42−4.48(m,1H),4.28−4.38(m,1H),4.22−4.28(m,1H),3.94−4.04(m,2H),2.54(br s,3H),2.23(br s,1H),0.98(d,J=7.0,3H), 0.88(d,J=7.0,3H).
C16H23N5O7S・HClに対する元素分析:計算値:C,41.25;H,5.02;N,15.03;S,6.88;Cl,7.61;実測値:C,40.57;H,5.37;N,13.57;S,6.16;Cl,7.29.
スキーム2は5−アミノ−7−メトキシ−3−β−D−リボフラノシルチアゾロ[4,5−d]ピリミジン−2−オン及び5,7−ジアミノ−3−β−D−リボフラノシルチアゾロ[4,5−d]ピリミジン−2−オンを調製するための一般的な手順を示している。
融点>160℃(分解(dec));[M+H]+ 330.9,[2M+H]+ 661.1,[3M+H]+ 991.0;Rf=0.6(20%MeOH−CHCl3);融点200.4℃−200.9℃;1H NMR(400MHz,d6−DMSO)δ6.92(s, 2H),5.86(d,J=5.2,1H),5.28(d,J=5.6,1H),4.96 (d,J=5.2,1H),4.78(dd,J=10.8,5.6,1H),4.67(t,J=6.0,1H),4.07−4.10(m,1H),3.91(s,3H),3.70−3.80(m,1H),3.55−3.60(m,1H),3.40−3.45(m,1H).
C11H14N4O6Sに対する元素分析:計算値:C,40.00;H,4.27;N,16.96;S,9.71;実測値:C,40.07;H,4.43;N,16.71;S,9.53.
融点>155℃(分解(dec));[M+H]+ 316.0;Rf=0.25(SiO2、 20%MeOH−CHCl3);1H NMR(400MHz,d6−DMSO)δ6.76 (s,2H),6.14(s,2H),5.85(d,J=5.2,1H),5.22(d, J=4.8,1H),4.92(d,J=2.8,1H),4.70−4.83(m,2H), 4.05−4.10(m,1H),3.65−3.80(m,1H),3.52−3.62 (m,1H),3.40−3.50(m,1H).
C10H13N5O5S・1/2H2Oに対する元素分析:計算値:C,37.03;H,4.35;N,21.59;S,9.89;実測値:C,37.27;H,4.32;N,20.43;S, 10.11.
融点246.7−248.1℃; Rf=0.20(SiO2,50%EtOAc−CHCl3);1H NMR(400MHz,d6−DMSO)δ12.23(s,1H),11.85(s,1H),5.97(m,2H),5.48(t,J=6,1H),4.35−4.40(m,1H),4.25−4.31(m,1H),4.08−4.18(m,1H),2.49(s,3H),2.07(s,3H),2.01(s,3H),2.00(s,3H).
74.5−76.3℃;Rf=0.7(SiO2,20% EtOAc−CHCl3);1H(400MHz,d6−DMSO)δ10.83(s,1H),7.39(s,2H),6.03(d,J=4.0,1H),5.91−5.96(m,1H),5.69(t,J=6.4,1H),4.30−4.70(m,1H),4.22−4.26(m,1H),4.16−4.20(m,1H),3.90−4.00(m,2H),2.97−3.01(m,1H),2.07(s,3H),2.06(s,3H),2.04(s,3H),1.88(s,3H),1.17−1.25(m,18H).
[M+H]+498.2,[2M+H]+995.4;Rf=0.55(10%CH3OH−CHCl3);1H NMR(400MHz,d6−DMSO)δ10.13(s,1H), 7.70(d,J=4.41,1H),5.95−6.02(m,2H),5.69(s, 1H),4.35−4.39(m,1H),4.16−4.23(m,2H),2.90(d,J=4.8,3H),2.20(s,3H),2.07(s,3H),2.02(s,3H),2.00(s,3H).
[M+H]+ 330.0;Rf=0.20(5%MeOH−EtOAc);融点>108℃; 1H NMR(400MHz,d6−DMSO)δ7.06(d,J=3.6,1H),6.24(s,2H),5.85(d,J=5.2,1H),5.22(d,J=4.8,1H),4.93(d,J=5.2,1H),4.70−4.80(m,2H),4.07(d,J=4.8,1H),3.75(d,J=4.4,1H),3.5−3.6(m,1H),3.40−3.50(m,1H),2.82(d,J=4.4,3H).
M+ 511.14;Rf=0.70(SiO2,10%MeOH−CHCl3);1H NMR(400MHz,d6−DMSO)δ10.15(s,1H),6.10−6.15(m, 1H),5.98−6.09(m,1H),5.5.66−5.70(m,1H),4.35−4.40(m,1H),4.22−4.27(m,1H),4.14−4.08(m,1H),3.18(s,6H),2.19(s,3H),2.08(s,3H),2.06(s,3H),1.99(s,3H).
[M+H]+ 344.0;[2M+H]+ 687.4;融点>112℃;Rf=0.20 (5%MeOH−EtOAc);1H NMR(400MHz,d6−DMSO)δ6.27(s,2H),5.91(d,J=4.8,1H),5.22(d,J=6.0,1H), 4.93(d,J=5.2,1H),4.71−4.76(m,2H),4.07−4.09(m,1H),3.7−3.8(m,1H),3.5−3.6(m,1H),3.5−3.6(m,1H),3.09(s,6H).
C12H17N5O5Sに対する元素分析:計算値:C,41.98;H,4.99;N,20.40;測定値:C,41.32;H,5.14;N,18.59.
Rf=0.45(SiO2,75%EtOAc−CHCl3);1H NMR(400MHz, d6−DMSO)δ10.11(s,1H),7.87(d,J=2.8,1H),5.98−6.01(m,1H),5.70−5.76(s,1H),4.32−4.39(m, 1H),4.16−4.30(m,2H),3.85(s,1H),2.87(s,1H),2.25(s,3H),2.07(s,3H),2.06(s,3H),1.98(s,3H),0.73−0.76(m,2H),0.57−0.60(m,2H).
Rf=0.20(5%MeOH−EtOAc);融点>100℃;[M+H]+ 356.0;1H(400MHz,d6−DMSO)δ7.24(s,1H),6.28(s,2H),5.86(d,J=5.6,1H),5.22(d,J=6,・1H),4.92(d,J=5.2,1H),4.70−4.80(m,2H),4.05−4.10(m,1H),3.7−3.8(m,1H),3.5−3.6(m,1H),3.45−3.50(m,1H),2.8(s,1H),0.68−0.70(m,2H),0.54−0.57(m,2H).
激しく攪拌している4M HCl/ジオキサン溶液に上記工程2で調製した固体物質を添加することにより表題の化合物を白色固体として得た。
融点>99℃;1H NMR(400 MHz,d6−DMSO)δ7.25(d,1H, J=2.8,1H),6.23(s,2H),5.87(d,J=5.2,1H),5.21(bs,1H),4.98(bs,1H),4.73−4.79(m,2H),4.09(t, J=5.6,1H),3.72−3.79(m,1H),3.55−3.60(m,1H), 3.45−3.37(m,1H), 2.75−2.82(m,1H),0.72−0.79(m,2H),0.55−0.63(m,2H).
C13H17N5O5S.HClに対する元素分析:計算値:C,39.85;H,4.63; N,17.87;Cl,9.05;測定値:C,39.66;H,4.85;N,16.57;Cl,8.13.
融点>108℃(分解(dec));Rf=0.80(10%水及び20%メタノール in 酢酸エチル);[M+H]+384.0;1H NMR(400MHz,d6−DMSO)δ7.00(d,J=7.2,1H),6.17(s,2H),5.18(d,J=5.2,1H),5.21(d,J=5.6,1H),4.92(d,J=5.6,1H),4.74−4.80(m,2H),4.30−4.35(m,1H),4.05−4.10(m,1H),3.70−3.80(m,1H),3.55−3.60(m,1H),3.30−3.45(m,1H),1.40−2.0(m,8H).
融点>108℃(分解(dec); Rf=0.80(10%水及び20%メタノール in 酢酸エチル);[M+H]+ 384.0;1H NMR(400MHz, d6−DMSO)δ7.00(d,J=7.2,1H),6.17(s,2H),5.18(d,J=5.2,1H),5.21(d,J=5.6,1H),4.92(d,J=5.6,1H),4.74−4.80(m,2H),4.30−4.35(m,1H),4.05−4.10(m,1H),3.70−3.80(m,1H),3.55−3.60(m,1H),3.30−3.45(m,1H),1.40−2.0(m,8H).
[M+H]+ 538.1;Rf=0.80(SiO2,水−MeOH−EtOAc,10:20:70);1H(400MHz,d6−DMSO)δ10.04(s,1H),5.97−6.02(m,2H),5.68(s,1H),4.38(dd,J=11.6,3.6, 1H),4.15−4.23 (m,2H),3.58(s,4H),2.23(s,3H),2.08(s,3H),2.05(s,3H),1.98(s,3H),1.89(s,4H).
融点>112.4℃(分解(dec));[M+H]+ 370.3;1H NMR(400MHz,d6−DMSO)δ6.22(s,2H),5.90(d,J=4.8,1H), 5.23(d,J=5.2,1H),4.94(d,J=4.4,1H),4.68−4.75(m,2H),4.08(d,J=4.8,1H),3.71−3.76(m,1H), 3.55(bs,5H),3.38−3.54(m,1H),1.87(s,4H).
5−アミノ−7−シクロペンチルアミノ−3−(2’,3’−O−イゾプロピリデン−β−D−リボフラノシル)チアゾロ[4,5−d]ピリミジン−2−オン(A)
化合物AはKiniらの方法に従い、5−アミノ−7−シクロペンチルアミノ−3−β−D−リボフラノシルチアゾロ[4,5−d]ピリミジン−2−オン22とアセトン、DMSO、メタンスルホン酸及び過剰量のジメトキシプロパンの混合物を出発原料が消費されるまで0℃で攪拌することにより調製する。反応混合物を氷水に加え、飽和NaCO3でpH7にまで中和し、EtOAcで抽出する。有機層を濃縮し、シリカでカラムクロマトグラフィーを行なって、2’,3’−保護ジオール生成物を得る。
1.0当量の(N−tert−ブトキシカルボニル)−L−バリンのTHF溶液に0℃で1.1当量のEDCを加える。30分の攪拌後、1.0当量の5−アミノ−7−シクロペンチルアミノ−3−(2’,3’−O−イゾプロピリデン−β−D−リボフラノシル)チアゾロ[4,5−d]ピリミジン−2−オン、A、と1.5当量のDMAPを加える。反応混合物を室温にまて昇温し、5時間攪拌して濃縮する。残渣をEtOAc中に溶解させ、1N HClで分液し、飽和NaHCO3水溶液(10mL)で中和する。水相を更にEtOAcで抽出する。集めた有機層をNa2SO4で乾燥し、濾過し、減圧下で溶媒を蒸発させて、シリカでのカラムクロマトグラフィーにより精製して中間体Bを得る。
化学式Iの化合物の、有利な経口送達特性を発揮する能力及び選択した経路で投与した場合の免疫反応を誘導する能力は、マウスおよびビーグル犬での実験で容易に実証できた。化学式Iの化合物に対する測定結果は、薬物動態学的性質及び薬力学的性質に関しての化学式Iの化合物の有利な点を明らかにするために、本明細書の開示の中で参照している文献(例えば米国特許第5041426号明細書及び米国特許第4880784号明細書等)に記載の化合物を用いた同様の実験の結果と比較することができる。
標準マウスは、本明細書に述べられている発明が1(イサトリビン(isatoribine))の経口送達においてどの程度の物質改善をもたらすかを評価するのに有用な系を提供するものである。上記プロドラッグを経口投与することで生じるイサトリビンの血漿濃度を測定することができるばかりでなく、マウスにおいて行なわれる広範囲にわたる免疫学的調査によってイサトリビンの所望の生物活性の一つを反映する、関心の高いインターフェロンα、サイトカインの量を測定するのに好適な試薬が提供されてきた。
プロドラッグ(val−イサトリビン、3)をビーグル犬への経口投与した後の、イサトリビン(1)への全身曝露に関する効果を調べた。イサトリビンを炭酸水素ナトリウム溶液中で調製した。Val−イサトリビン及びイサトリビンは、溶解性を確保するために選択された次の処方によって調製した。
処方1:イサトリビンの炭酸水素ナトリウム溶液、1mg/mL及び4mg/mL。
処方2:リン酸緩衝生理食塩水中のval−イサトリビン、1.62mg/mL及び6.48mg/mL(それぞれ1mg/mL及び4mg/mLのイサトリビンとモル基準で等量)。
注射により投与するのに好適な非経口投与用医薬組成物を調製するために、化学式Iの化合物の水溶性の塩100mgをDMSO中に溶解させ、その後10mLの0.9%滅菌生理食塩水と共に混合する。その混合物を注射での投与に好適な単位剤形に入れる。
経口送達用の医薬組成物を調製するのに、化学式Iの化合物100mgを750mgのラクトースと混合する。その混合物を、例えば硬質ゼラチンカプセル等の経口投与に適した単位剤形に入れる。
Claims (18)
- R1基のうち少なくとも一つはラセミ、L−又はD−体のアミノ酸基−C(O)CH(R 4 )NH 2 であり、そのうちR4は置換又は無置換のアルキル基であり、残りのR1基はHである;R2はOR 5 である請求項1に記載の化合物又は薬学的に許容される塩。
- R 5 はアルキル基である請求項2に記載の化合物又は薬学的に許容される塩。
- R 4は−CH(CH3)2基であり、R 2はOHである請求項2に記載の化合物又は薬学的に許容される塩。
- R 2 はHである請求項1に記載の化合物又は薬学的に許容される塩。
- R 1 はHであり、R 2 はHである請求項1に記載の化合物又は薬学的に許容される塩。
- R1基のうち少なくとも一つはラセミ、L−又はD−体のアミノ酸基−C(O)CH(R 4 )NH 2 であり、このうちR4は置換又は無置換のアルキル基であり、残りのR1基はHである;R2はOR 5 である請求項8に記載の医薬組成物。
- R 5 はアルキル基である請求項9に記載の医薬組成物。
- R 4は−CH(CH3)2基であり、R 2はOHである請求項9に記載の医薬組成物。
- R 2 はHである請求項8に記載の医薬組成物。
- R 1 はHであり、R 2 はHである請求項8に記載の医薬組成物。
- 請求項1〜7のいずれか1項に記載の化合物を含有することを特徴とする、インターフェロン反応誘発剤。
- 請求項1〜7のいずれか1項に記載の化合物を含有することを特徴とする、抗ウィルス剤又は抗腫瘍剤。
- 治療する疾患が、アデノウィルス、サイトメガロウィルス、A型肝炎ウィルス(HAV)、B型肝炎ウィルス(HBV)、黄熱ウィルス、C型肝炎ウィルス(HCV)、単純ヘルペスウィルス1型若しくは2型、帯状疱疹、ヒトヘルペスウィルス6、ヒト免疫不全ウィルス(HIV)、ヒト乳頭腫ウィルス(HPV)、A型インフルエンザウィルス、B型インフルエンザウィルス、はしか、パラインフルエンザウィルス、ポリオウィルス、痘ウィルス、天然痘ウィルス、サル痘ウィルス、ライノウィルス、呼吸器多核体ウィルス(RSV)、出血熱の原因となるウィルス、アレナウィルス、ブニヤウィルス、フィロウィルス、脳炎ウィルス、西ナイルウィルス、ラクロスウィルス、カリフォルニア脳炎ウィルス、ベネズエラウマ脳炎ウィルス、東部ウマ脳炎ウィルス、西部ウマ脳炎ウィルス、日本脳炎ウィルス、キャサヌール森林ウィルス、又は、ダニ媒介ウィルスが原因となる感染症であることを特徴とする請求項16に記載の抗ウィルス剤又は抗腫瘍剤。
- 治療する疾患が、C型肝炎ウィルス(HCV)が原因となる感染症であることを特徴とする請求項17に記載の抗ウィルス剤又は抗腫瘍剤。
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