CN1834095A - 一类非核苷类抗病毒抑制剂及其制备方法和用途 - Google Patents
一类非核苷类抗病毒抑制剂及其制备方法和用途 Download PDFInfo
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- CN1834095A CN1834095A CNA2005100244685A CN200510024468A CN1834095A CN 1834095 A CN1834095 A CN 1834095A CN A2005100244685 A CNA2005100244685 A CN A2005100244685A CN 200510024468 A CN200510024468 A CN 200510024468A CN 1834095 A CN1834095 A CN 1834095A
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- Prior art keywords
- alkyl
- benzyl
- phenyl
- substituted
- formyl radical
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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Abstract
Description
样品编号 | CytotoxicityCC50(uM) | HbsAg secretionIC50(SI)(uM) | HBeAg secretionIC50(SI)(uM) | DNA replicationIC50/ICX(SI)(uM) |
Wang338Wang278Wang282-1Wang282Wang278-1Wang405.49 | 200.3152.7>333396.990.3154.1 | 77.6(2.58)67.35(2.27)67.57(>4.93)58.8(6.75)34.1(2.6)63.5(2.43) | 22.3(9)24(6.4)21.67(>15.4)57.3(6.9)19(4.8)46(3.32) | 6.1(32.8)4.8(32.1)2.4(>138.8)19.4(20.5)IC88=1.3776(2.02) |
样品编号 | CytotoxicityCC50(uM) | HbsAg secretionIC50(SI)(uM) | HBeAg secretionIC50(SI)(uM) | DNA replicationIC50/ICX(SI)(uM) |
Wang279-1Wang265Wang240Wang260Wang268Wang268-1Wang298Wang316 | 785.7548.5611.4269.7256.7437.3568.6173.6 | 142.6(5.5)130.8(4.2)63.9(9.6)71.4(3.8)37.2(6.9)90(4.9)143.5(4)33.7(5.2) | 102.1(7.7)38.8(14.1)182.1(3.4)130(3.1)127.7(2)100.7(4.3)209.4(2.7)70.5(2.5) | IC60=37IC44=4.1IC34=31.3IC85=37IC53=125153.1(2.9)NCIC20=31.3 |
样品编号 | CytotoxicityCC50(uM) | HbsAg secretionIC50(SI)(uM) | HBeAg secretionIC50(SI)(uM) | DNA replicationIC50/ICX(SI)(uM) |
Wang261Wang264Wang302Wang294Wang417.46-JWang529.61-1Wang337.40 | 123.3124.5192.2>1000754.6472.04740.1 | 92.4(1.3)41.3(3)NC>1000143.0(5.3)214(2.21)NC | 37(3.3)95.5(1.3)83.2(2.3)1139(>0.88)NC171.1(2.76)NC | NCNC63.1(3.1)IC60=37NCNC351.1(2.11) |
编号 | TC50 | 抗泡疹病毒IHSV-I(IC50)(SI) | 抗泡疹病毒IIHSV-II(IC50)(SI) |
Wang363.43-1Wang417.46-PWang443.52Wang577.72Wang529.61-1Wang501.56-1ACV | 707.11198.43168.24176.78198.43707.11>1000 | 369.21(1.92)-106.52(1.52)---12.92(>77.39) | -106.52(1.86)78.75((1.86)97.59(1.81)106.52293.37(2.41)10.58(>94.51) |
化合物 | TC50 | 抗流感甲型病毒(IC50) | 化合物 | TC50 | 抗流感甲型病毒(IC50) |
Wang363.43-1Wang391.49-1Wang417.46-PWang399.46Wang363.43-2Wang443.52Wang529.61-1Wang551.62Wang501.56-1Wang537.59Wang403.50Yao351.42Yao405.51Wang415.46 | 500250422.43166.67500165.86191.74303.69303.69>1000333.33577.35577.35333.33 | 3.970.560.901.140.421.293.151.181.181.2964.15258.6837.0329.01 | Yao379.47Wang391.49-2Wang377.46-1Wang417.46-JWang377.46-2Wang501.56-2Wang555.65Wang417.52Wang429.49Wang529.61-2Wang489.55Wang543.64-1Wang389.47Ribavirin | 577.35>1000500>1000577.35577.35577.35231.12333.33577.35577.35144.34480.75>2000 | 97.81>192.45111.11>86.23258.6968.7144.4868.7147.72111.11160.2557.7829.013.73 |
编号 | HIV-1蛋白酶(IC50) | HIV-1整合酶(IC50) |
Wang399.46Wang577.72阳性对照 | -33.390.1(奈非那韦) | 145.8-0.48(ABPS-y) |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang279 | δ0.93(t,3H),1.39~1.46(m,5H),1.69(m,2H),2.99(t,2H),4.38(q,2H),7.42(d,1H),7.83(d,1H). |
Wang279-1 | δ0.86(d,6H),1.34(t,3H),1.94(m,1H),2.79(d,2H),4.33(q,2H),7.39(d,1H),7.78(d,1H). |
Wang278 | δ0.89(t,3H),1.28~1.45(m,5H),1.66(m,2H),2.94(t,2H),4.31(q,2H),7.01(dd,1H),7.30(d,1H),7.60(d,1H). |
Wang292 | δ0.87(t,3H),1.28~1.43(m,7H),1.67(m,2H),2.91(t,Hz,2H),4.35(q,2H),7.06(dd,1H),7.34(d,1H),7.49(d,1H). |
Wang264-1 | δ1.25~1.34(m,9H),3.69(m,1H),4.33(q,2H),7.03(dd,1H),7.30(d,1H),7.53(d,1H). |
Wang265-1 | δ1.26(d,6H),1.39(t,3H),3.87(m,1H),4.38(q,2H),7.37(d,1H),7.75(d,1H). |
Wang265 | δ0.98(t,3H),1.40(t,3H),1.75(m,2H),2.92(t,2H).4.39(q,2H),7.43(d,1H),7.84(d,1H). |
Wang223 | δ2.56(s,3H),3.88(s,3H),7.41(d,1H),7.80(d,1H). |
Wang222-1 | δ2.53(s,3H),3.80(s,3H),6.96(dd,1H),7.24(d,1H),7.58(d,1H). |
Wang278-1 | δ0.95(d,6H),1.35(t,3H),2.08(m,1H),2.83(br,2H),4.34(q,2H),7.26(d,1H),7.34(d,1H),7.57(m,1H). |
Wang404 | δ0.87(3H),1.2-1.60(22H),1.40-1.69(4H),2.87(2H),4.37(q,2H),7.09(m,1H),7.26(m,1H),7.46(m,1H). |
Wang276 | δ1.23(t,3H),2.39(dd,2H),3.02(t,2H),4.29(q,2H),4.91(d,1H),4.96(d,1H),5.74-5.85(m,1H),7.00(dd,1H),7.27(d,1H),7.57(d,1H). |
Wang350 | δ1.42(t,3H),4.22(q,2H),7.02(ddd,1H),7.10(dd,1H),7.18(dd,1H),7.40(dd,1H),7.45(dd,1H),7.64(d,1H). |
Wang264 | δ0.95(t,3H),1.71(m,2H),2.87(m,2H),4.32(q,2H),7.05(m,1H),7.30(m,1H),7.51(m,1H). |
Wang298 | δ1.19(t,3H),4.24(q,2H),7.01(m,1H),7.31(5H),7.58(d,1H),7.74(m,1H). |
Wang298-1 | δ3.81(s,3H),7.07(dd,1H),7.36(5H),7.58(d,1H),7.80(dd,1H). |
Chen262 | δ0.94~1.10(m,4H),1.38(t,3H),2.56(m,1H),4.38(q,2H),7.05(dd,1H),7.33(d,1H),7.49(d,1H). |
Chen263 | δ0.82~0.88(4H),1.43(t,3H),2.57(m,1H),4.35(q,2H),7.39(d,1H),7.84(d,1H),10.56(bs,NH). |
Chen277 | δ1.38(t,3H),2.04(m,2H),2.37(m,4H),4.09(m,1H),4.36(q,2H),7.41(d,1H),7.82(d,1H). |
Chen291 | δ1.40(t,3H),1.56~1.90(8H),3.89(m,1H),4.39(q,2H),7.36(d,1H),7.54(d,1H),11.06(bs,NH). |
Chen324 | δ1.47(t,3H),4.44(q,2H),7.13(dd,1H),7.28~7.48(m,3H),7.55~7.60(m,3H),7.66(d,1H),9.77(bs,NH). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang296 | δ0.95(t,3H),1.35~1.48(m,5H),1.78(m,2H),3.13(t,2H),4.42(q,2H),7.45(dd,1H),7.80(d,1H). |
Wang421 | δ0.87(3H),1.25-1.45(22H),1.68-1.76(4H),3.22(t,2H),4.41(q,2H),7.06(dd,1H),7.39(dd,1H),7.48(dd,1H). |
Chen321.09 | δ1.16~1.49(7H),1.72~1.83(4H),2.04(m,2H),3.74(m,1H),4.39(q,2H),7.02(dd,1H),7.35(d,1H),7.45(d,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang280.09 | δ0.94(t,3H),1.35~1.48(m,5H),1.76(m,2H),3.13(t,2H),4.42(q,2H),7.52(d,1H),7.96(d,1H). |
Wang279.09 | δ0.94(t,3H),1.33~1.44(bm,5H),1.73(m,2H),3.07(t,2H),4.40(q,2H),7.10(dd,1H),7.43(d,1H),7.72(d,1H). |
Chen263 | δ1.42(t,3H),2.00(d,3H),4.42(q,2H),6.64(m,1H),6.96(d,1H),7.11(dd,1H),7.45(d,1H),7.76(d,1H). |
Chen325 | δ1.47(t,3H),4.47(q,2H),7.15(dd,1H),734~7.43(m,3H),7.50(d,1H),7.58~7.67(m,2H),7.85(d,1H). |
Chen305 | δ1.22~1.45(m,7H),1.54~1.75(m,2H),1.82~1.93(m,4H),3.47(m,1H),4.38(q,2H),7.08(dd,1H),7.41(d,1H),7.69(d,1H). |
Chen277 | δ7.14(dd,1H),7.32~7.37(m,1H),740(s,1H),7.42~7.47(m,3H),7.69~7.72(m,2H),7.73(d,1H). |
Chen321 | δ0.91~1.00(m,6H),1.37~1.45(m,5H),1.65~1.76(m,4H),2.78(t,2H),3.05(t,2H),4.40(q,2H),6.77(d,1H),7.53(d,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang282-1 | δ0.99(d,6H),1.99(m,1H),3.15(d,2H),3.96(s,3H),7.46(d,1H),7.86(d,1H). |
Wang368 | δ4.00(s,3H),4.70(s,2H),6.96(dd,1H),7.65(d,1H),7.33(dd,1H),7.46(d,1H),7.83(d,1H). |
Wang354 | δ3.83(s,3H),7.09(dd,1H),7.29(d,1H),7.41(dd,1H),7.54(d,1H),7.92(d,1H). |
Wang240 | δ1.38(t,3H),4.40(q,2H),7.48(d,1H),7.86(d,1H),8.20(s,1H). |
Wang222 | δ1.89(t,4H),2.83(m,4H),7.37(d,1H),7.83(d,1H). |
Wang284 | δ3.41(s,3H),3.55(t,2H),3.68(t,2H),3.96(s,3H),7.46(d,1H),7.88(d,1H). |
Wang316 | δ3.98(s,3H),4.60(s,2H),7.30(5H),7.43(d,1H),7.82(d,1H). |
Wang352 | δ4.00(s,3H),4.72(s,2H),6.97(ddd,1H),7.17(dd,1H),7.25(s,1H),7.34(dd,1H),7.77(s,1H) |
Wang338 | δ3.84(s,3H),7.09(ddd,1H),7.28(dd,1H),7.33(d,J=0.6Hz,1H),7.4(dd,1H),7.84(d,1H). |
Wang354 | δ3.83(s,3H),7.10(ddd,1H),7.28(dd,1H),7.41(dd,1H),7.54(d,1H),7.93(d,1H). |
Wang368 | δ4.00(s,3H),4.70(s,2H),6.96(ddd,1H),7.17(dd,1H),7.33(dd,1H),7.46(d,1H),7.84(d,1H). |
Wang282 | δ0.92(t,3H),1.45(tq,2H),1.70(tt,2H),3.25(t,2H),3.92(s,3H),7.43(dd,1H),7.84(d,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang261 | δ7.34(d,1H),7.40(m,3H),7.63(d,1H),7.69(d,2H). |
Wang260 | δ7.00(dd,1H),7.35(m,4H),7.59(dd,1H),7.72(dd,2H). |
Wang241 | δ0.77(t,3H),1.16(m,2H),1.23(m,3H),2.48(t,2H),7.36(d,1H),7.44(d,1H),12.27(bs,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang268 | δ0.76(t,3H),1.13(m,2H),1.38(m,2H),2.47(t,2H),7.36(d,1H),7.74(d,1H). |
Wang302 | δ4.89(s,2H),7.27(5H),7.38(d,1H),7.80(d,1H). |
Wang268-1 | δ0.11(d,6H),2.03(m,1H),3.33(d,2H),7.40(d,1H),7.80(d,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang363.43-1 | δ0.68-0.79(4H),0.92(3H),0.95(d,3H),1.44-1.49(1H),2.35-2.42(1H),2.70(3H),3.91(3H),5.23(1H),6.58(1H),7.95(s,1H). |
Yao393.50 | δ0.82(3H),0.89(d,3H),0.90(d,3H),1.26(m,4H),1.59(m,2H),2.22(t,2H),2.36(m,1H),2.67(s,3H),3.89(s,3H),5.20(dd,1H),6.40(d,1H),7.93(s,1H) |
Wang391.49-1 | δ0.92(d,6H),1.56(m,2H),1.69-1.87(6H),240(m,1H),2.61(m,1H),2.69(s,3H),3.90(s,3H),5.22(dd,1H),6.29(d,1H),7.95(s,1H) |
Wang377.46-1 | δ0.92(d,3H),0.93(d,3H),2.01(m,2H),2.18(m,2H),2.26(m,2H),2.40(m,1H),2.71(s,3H),3.08(m,1H),3.92(s,3H),5.22(dd,1H),6.15(d,1H),7.96(s,1H) |
Wang405.51-1 | δ0.91(d,6H),1.19-1.28(m,2H),1.43(m,2H),1.65-1.84(m,6H),2.17(m,1H),2.40(m,1H),2.69(s,3H),3.90(s,3H),5.22(dd,1H),6.32(d,1H),7.95(s,1H); |
Wang417.46-J | δ1.01(d,3H),1.06(d,3H),2.52(m,1H),2.73(s,3H),3.94(s,3H),5.42(dd,1H),7.10(d,1H),7.16(ddd,1H),7.40(ddd,1H),7.55(ddd,1H),7.58(d,1H),7.99(s,1H). |
Wang417.47-p | δ1.01(d,3H),1.06(d,3H),2.52(m,1H),2.73(s,3H),3.94(s,3H),5.42(dd,1H),7.10(d,1H),7.16(ddd,1H),7.40(ddd,1H),7.55(ddd,1H),7.58(d,1H),7.99(s,1H). |
Wang443.52 | δ0.94(d,3H),0.95(d,3H),2.50(m,1H),2.68(s,3H),3.92(s,3H),3.99,4.07(dd,2H),4.59,4.64(dd,2H),5.24(dd,1H),7.29-7.34(5H),8.00(s,1H) |
Yao351.42 | δ0.88(d,3H),0.90(d,3H),1.24(t,3H),2.26(q,3H),2.38(m,1H),2.66(s,3H),3.88(s,3H),5.19(dd,1H),6.44(d,1H),7.92(s,1H) |
Wang413.49 | δ0.75(d,3H),0.86(d,3H),2.38(m,1H),2.70(s,3H),3.64(s,2H),3.91(s,3H),5.19(dd,1H),6.24(d,1H),7.27-7.38(5H),7.95(s,1H) |
Yao379.47 | δ0.88(d,3H),0.94(d,3H),1.94(s,9H),2.47(m,1H),2.66(s,3H),3.88(s,3H),5.18(m,1H),6.32(d,1H),7.94(s,1H) |
Yao337.40 | δ0.88(d,3H),0.91(d,3H),2.03(s,3H),2.33(m,1H),2.67(s,3H),3.88(s,3H),5.18(dd,1H),6.60(d,1H),7.92(s,1H) |
Wang489.16 | δ1.01(d,3H),1.07(d,3H),2.57(m,1H),2.72(s,3H),3.87(s,3H),3.92(s,9H),5.40(dd,1H),6.99(d,1H),7.13(s,2H),8.01(s,1H). |
Wang399.46 | δ1.02(d,3H),1.06(d,3H),2.55(m,1H),2.73(s,3H),3.94(s,3H),5.46(dd,1H),6.95(d,1H),7.44-7.54(m,3H),7.84(d,2H),8.01(s,1H) |
Wang465.12 | δ2.72(s,3H),3.46(d,2H),3.91(s,1H),5.85(d,1H),7.07~7.14(m,2H),7.18~7.26(2H),7.44(m,2H),7.95(s,1H),8.01(dd,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang363.43-2 | δ0.90(d,3H),0.91(d,3H),2.45(m,1H),2.69(s,3H),3.05-3.08(m,2H),3.90(s,3H),5.16-5.26(m,3H),5.87-6.00(m,1H),6.47(d,1H),7.96(s,1H). |
Wang403.50 | δ0.89(d,3H),0.92(d,3H),1.89(m,2H),2.27-2.37(m,4H),2.44(m,1H),2.69(s,3H),3.10(s,2H),3.91(s,3H),5.20(dd,6.3Hz,1H),5.63(m,1H),6.51(d,1H),7.91(s,1H) |
Wang417.52 | δ0.89(d,3H),0.93(d,3H),1.55-1.64(m,4H),1.97(m,2H),2.07(m,2H),2.46(m,1H),2.70(s,3H),2.94(s,2H),3.92(s,3H),5.21(dd,6.0Hz,1H),5.69(brs,1H),6.59(d,1H),7.99(s,1H) |
Wang377.46-2 | δ0.88(d,3H),0.89(d,3H),2.30-2.35(5H),2.67(s,3H),3.88(s,3H),4.94(dd,1H),5.01(dd,1H),5.19(dd,1H),5.76(m,1H),6.50(d,1H),7.92(s,1H) |
Wang391.49-2 | δ0.87(d,3H),0.92(d,3H),1.66(s,3H),1.79(s,3H),2.44(m,1H),2.69(s,3H),3.01(d,2H),3.91(s,3H),5.19(dd,1H),5.33(t,1H),6.51(d,1H),7.97(s,1H) |
Yao405.51 | δ0.89(d,3H),0.90(d,3H),1.56(s,3H),1.61(s,3H),2.23-2.67(m,5H),2.74(s,3H),3.89(s,3H),5.05(m,1H),5.20(dd,1H),6.45(d,1H),7.94(s,1H) |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang405.49 | δ0.97(d,3H),1.03(d,3H),2.51(m,1H),2.71(s,3H),3.92(s,3H),5.35(dd,1H),6.87(d,1H),7.07(dd,1H),7.49(d,1H),7.60(d,1H),7.98(s,1H). |
Wang515.18 | δ1.01(d,6H),1.46(s,9H),2.67(m,1H),2.69(s,3H),3.90(s,3H),5.33(dd,6Hz,1H),7.38(dd,1H),8.15(dd,1H),8.82(dd,1H),9.05(d,1H),11.01(s,1H) |
Wang429.49 | δ0.97(d,3H),1.02(d,3H),2.62(m,1H),2.69(s,3H),3.89(s,3H),4.03(s,3H),5.49(dd,1H),6.99(d,1H),7.05(t,1H),7.44(dd,1H),7.96(s,1H),8.16(d,1H),8.70(d,1H) |
Yao414 | δ1.03(d,3H),1.04(d,3H),2.55(m,1H),2.73(s,3H),3.94(s,3H),5.42(dd,1H),6.69(d,1H),6.71(d,1H),6.83(d,1H),7.23(d,1H),7.45(d,1H),8.01(s,1H) |
Yao415 | δ1.00(d,3H),1.07(d,3H),2.52(m,1H),2.73(s,3H),3.94(s,3H),5.40(dd,1H),6.90(t,1H),6.99(d,1H),7.22(d,1H),7.42(t,1H),7.53(d,1H),8.02(s,1H). |
Wang577.72 | δ0.94(d,3H),1.01~1.06(9H),1.45(s,9H),2.39(m,1H),2.66(m,1H),2.73(s,3H),3.94(s,3H),4.90(m,1H),5.15(m,1H),5.36(dd,1H),7.93(d,1H),8.01(s,1H),8.04(s,1H). |
Yao453 | δ2.71(s,3H),3.43(m,2H),3.91(s,1H),5.75(d,1H),7.04(dd,1H),7.1~7.26(m,5H),7.45(d,1H),7.57(d,1H),7.92(s,1H). |
Yao363 | δ2.72(s,3H),3.92(s,3H),4.97(d,1H),6.81(m,1H),7.04(dd,1H)7.52(s,1H),7.57(d,1H),8.05(s,1H). |
Yao420 | δ0.97(d,3H),1.03(d,3H),2.51(m,1H),2.73(d,6H),3.94(s,3H),5.37(dd,1H),7.97(s,1H),8.00(s,1H). |
Yao485 | δ1.02(d,3H),1.03(d,3H),2.56(m,1H),2.72(s,3H),3.92(s,3H),5.35(dd,1H),7.84(dd,1H),8.00(s,1H),8.07(s,1H). |
Yao561 | δ1.02(d,3H),1.03(d,3H),2.60(m,1H),2.73(s,3H),3.93(s,3H),5.35(dd,1H),7.87(dd,1H),8.01(s,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang415.46 | δ1.02(d,3H),1.07(d,3H),2.67(m,1H),2.75(s,3H),4.07(s,3H),5.54(dd,1H),7.04(d,1H),7.11(dt,1H),7.48(td,1H),7.99(s,1H),8.22(dd,1H),8.75(d,1H). |
Wang377.46-OH | δ0.97(d,6H),1.60~1.89(8H),2.44(m,1H),2.62(m,1H),2.75(s,3H),5.26(dd,1H),6.26(d,1H),7.97(s,1H). |
Wang389.47 | δ0.94(d,3H),0.97(d,3H),1.88-1.99(m,2H),2.31-2.33(m,2H),2.37-2.44(m,2H),2.46-2.53(m,1H),2.75(s,3H),3.14(s,2H),5.24(dd,1H),5.67(m,1H),7.98(s,1H). |
Yao439 | δ2.72(s,3H),3.41(m,2H),5.86(d,1H),7.04(dd,1H),7.1~7.26(m,5H),7.45(d,1H),7.57(d,1H),7.92(s,1H). |
Yao451 | δ2.76(s,3H),3.50(d,2H),5.88(d,1H),7.09~7.13(m,3H),7.23~7.28(m,3H),7.48(m,2H),7.97(s,1H),8.04(dd,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang537.59 | δ1.01(d,3H),1.05(d,3H),1.68(d,3H),2.59(m,1H),2.7(s,3H),3.88(s,3H),5.46(m,1H),5.49(m,1H),6.97(d,1H),7.41-7.54(m,4H),7.81-7.83(m,1H),7.82(d,1H),7.87(s,1H),8.17(s,1H). |
Wang531.63 | δ0.86(m,3H),0.96(d,6H),1.31(m,4H),1.63(m,2H),1.67(d,3H),2.26(t,2H),2.46(m,1H),2.71(s,3H),3.90(s,3H),5.25(dd,1H),5.50(m,1H),6.26(d,1H),7.52(d,1H),7.86(s,1H),8.18(s,1H) |
wang517.60 | δ0.94(d,3H),0.97(d,3H)1.25(s,9H),1.69(d,3H),2.56(m,1H),2.71(s,3H),3.89(s,3H),5.24(dd,6.0Hz,1H),5.49(m,1H),6.30(d,1H),7.52(d,1H),7.85(s,1H),8.17(s,1H) |
Wang475.52 | δ0.95(d,3H),0.97(d,3H)1.69(d,3H),2.08(s,3H),2.42(m,1H),2.71(s,3H),3.90(s,3H),5.23(dd,1H),5.50(m,1H),6.39(d,1H),7.54(d,1H),7.86(s,1H),8.18(s,1H) |
Wang489.55 | δ0.94(d,3H),0.95(d,3H),1.70(t,3H),2.30(q,2H),2.43(m,1H),2.70(s,3H),3.89(s,3H),5.24(dd,1H),5.49(m,1H),6.32(d,1H),7.53(d,1H),7.85(s,1H),8.17(s,1H) |
Wang515.58-3 | δ0.95(d,3H),0.96(d,3H)1.67(d,3H),1.75(d,3H),1.86(d,3H),2.51(m,1H),2.69(s,3H),3.87(s,3H),5.27(dd,1H),5.48(m,1H),6.42(d,1H),7.51(d,1H),7.84(s,1H),8.16(s,1H) |
Wang581.64 | δ0.94(d,3H),0.97(d,3H)1.66(d,3H),2.55(m,1H),2.70(s,3H),3.87(s,3H),4.00,4.07(dd,2H),4.59,4.64(dd,2H),5.26(dd,1H),5.47(m,1H),7.28-7.34(6H),7.51(d,1H),7.87(s,1H),8.15(s,1H). |
Wang555.58-J | δ1.00(d,3H),1.04(d,3H),1.67(d,3H),2.56(m,1H),2.70(s,3H),3.88(s,3H),5.40 |
(dd,1H),5.47(m,1H),7.07(d,1H),7.20(dd,1H),7.40(dd,1H),7.53~7.60(3H),7.88(s,1H),8.71(s,1H) | |
Wang551.62 | δ0.73(d,3H),0.86(d,3H),1.66(d,3H),2.41(m,1H),2.68(s,3H),3.63(s,2H),3.86(s,3H),5.19(dd,1H),5.47(m,1H),6.25(d,1H),7.25-7.36(5H),7.52(d,H),7.81(s,1H),8.15(s,1H) |
Wang501.56-1 | δ0.72-0.81(m,4H),0.94(d,3H),0.96(d,3H),1.48(m,1H),1.67(d,3H),2.45(m,1H),2.69(s,3H),3.87(s,3H),5.24(dd,1H),5.48(m,1H),6.60(d,1H),7.54(d,1H),7.84(s,1H),8.16(s,1H) |
Wang515.58-1 | δ0.93(d,6H),1.67(d,3H),1.96(m,2H),2.16-2.32(4H),2.44(1H),2.69(s,3H),3.09(m,1H),3.88(s,3H),5.22(dd,1H),5.52(m,1H),6.16(d,1H),7.52(d,1H),7.84(s,1H),8.16(s,1H) |
Wang555.58-J | δ1.02(d,3H),1.04(d,3H),1.68(d,3H),2.64(m,1H),2.70(s,3H),3.88(s,3H),5.46-5.54(m,2H),7.15(ddd,1H),7.26(td,1H),7.38(dd,1H),7.45-7.51(m,1H),7.52(d,1H),7.87(s,1H),8.06(td,1H),8.17(s,1H) |
Wang529.61-1 | δ0.94(d,3H),0.95(d,3H),1.55(m,3H),1.68(d,3H),1.72-1.92(m,5H),2.47(m,1H),2.61(m,1H),2.70(s,3H),3.89(s,3H),5.24(dd,1H),549(m,1H),6.26(d,1H),7.53(d,1H),7.84(s,1H),8.17(s,1H) |
Wang543.64-1 | δ0.93(d,3H),0.95(d,3H),1.26(m,4H),1.50(m,2H),1.68(d,3H),1.77(m,2H),1.88(m,2H),2.20(m,1H),2.47(m,1H),2.70(s,3H),3.88(s,3H),5.24(dd,1H),5.49(m,1H),6.25(d,1H),7.53(d,1H),7.84(s,1H),8.17(s,1H) |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang529.61-2 | δ0.92(d,3H),0.96(d,3H),1.68(s,3H),1.69(d,3H),1.80(s,3H),2.50(m,1H),2.71(s,3H),3.03(d,2H),3.90(s,3H),5.22(dd,1H),5.35(m,1H),5.50(m,1H),6.47(d,1H),7.51(d,1H),7.86(s,1H),8.17(s,1H). |
Wang501.56-2 | δ0.94(d,3H),0.95(d,3H)1.68(d,3H),2.47(m,1H),2.70(s,3H),3.08(ddd,2H),3.89(s,3H),5.20-5.28(3H),5.49(m,1H),5.96(m,1H),6.42(d,1H),7.52(d,1H),7.88(s,1H),8.17(s,1H). |
Wang515.58-2 | δ0.84(d,3H),0.95(d,3H),1.68(d,3H),2.39-2.47(5H),2.70(s,3H),3.89(s,3H),4.99(d,1H),5.06(d,1H),5.24(dd,1H),5.49(m,1H),5.81(m,1H),6.35(d,1H),7.52(d,1H),7.85(s,1H),8.16(s,1H) |
Wang543.64-2 | δ0.94(d,6H),1.60(s,3H),1.64(s,3H),1.68(d,3H)2.28-2.38(4H),2.44(m,1H),2.70(s,3H),3.89(s,3H),5.09(m,1H),5.24(dd,1H),5.49(m,1H),6.31(d,1H),7.51(d,1H),7.85(s,1H),8.16(s,1H). |
Wang541.62 | δ0.92(d,3H),0.96(d,3H),1.69(d,3H),1.92(m,2H),2.29~2.39(4H),2.49(m,1H),2.71(s,3H),3.12(s,2H),3.89(s,3H),5.23(dd,1H),5.56(m,1H),5.65(m,1H),6.46(d,1H),7.50(d,1H),7.86(s,1H),8.17(s,1H) |
Wang555.65 | δ0.91(d,3H),0.96(d,3H),1.57-1.65(m,4H),1.69(d,3H),1.99(m,2H),2.07(m,2H),2.51(m,1H),2.71(s,3H),2.95(s,2H),3.89(s,3H),5.22(dd,1H),5.51(dt,1H),5.70(m,1H),6.52(d,1H),7.50(d,1H),7.86(s,1H),8.17(s,1H) |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang715.84 | δ0.93(d,3H),1.00(d,3H),1.03(d,3H),1.04(d,3H),1.44(s,9H),1.70(d,3H),2.38(m,1H),2.72(s,3H),3.90(s,3H),4.90(m,1H),5.14(d,1H),5.37(dd,1H),5.50(m,1H),7.52(d,1H),7.88(s,1H),7.90(d,1H),8.03(s,1H),8.18(s,1H) |
Wang653.71 | δ1.04(d,3H),1.06(d,3H),1.50(s,9H),1.70(d,3H),2.67-2.72(m,1H),2.72(s,3H),3.90(s,3H),5.39(dd,1H),5.51(m,1H),7.42(dd,1H),7.53(d,1H),7.81(s,1H),8.18(dd,1H),8.86(dd,1H),9.08(d,1H),11.01(s,1H). |
Wang538.58 | δ1.04(d,3H),1.05(d,3H),1.70(d,3H),2.71(s,3H),2.68-2.74(m,1H),3.89(s,3H),5.45(dd,1H),5.50(m,1H),7.47(ddd,1H),7.55(d,1H),7.86(s,1H),7.87(td,1H),8.17(s,1H),8.20(dd,1H),8.60(ddd,1H),8.76(d,1H) |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang590.22 | δ0.90(d,3H),1.00(d,3H),1.44(s,9H),1.66(d,3H),2.49(m,1H),2.71(s,3H),3.76(s,3h),4.18(d,2H),4.49(m,1H),5.26(m,1H),5.45(m,1H),7.45(br,1H),7.57(d,1H),7.87(s,1H),8.14(s,1H). |
Wang604.23 | δ0.87(d,3H),0.96(d,3H),1.39(s,9H),1.60(d,3H),2.46(m,1H),2.58(t,2H),2.66(s,3H),3.61(t,3H),3.64(s,3H),4.90(m,1H),5.34(m,1H),5.41(m,1H),7.41(m,1H),7.56(d,1H),7.84(s,1H),8.08(s,1H) |
Wang646.28 | δ0.90(d,3H),0.99(d,3H),1.43(s,9H),1.59~1.69(m,6H),1.63(d,3H),2.29(t,2H),2.48(m,1H),2.70(s,3H),3.37(m,2H),3.63(s,3H),4.95(m,1H),5.27(m,1H),5.44(m,1H),7.01(m,1H),7.53(d,1H),7.84(s,1H),8.10(s,1H) |
Wang632.26 | δ0.86(d,3H),0.95(d,3H),1.39(s,9H),1.59(d,3H),1.55-1.65(m,4H),2.29(t,2H),2.43(m,1H),2.65(s,3H),3.51(m,2H),3.59(s,3H),4.90(m,1H),5.33(d,1H),5.39(m,1H),7.09(br,1H),7.57(d,1H),7.81(s,1H),8.08(s,1H). |
Wang618.25 | δ0.87(d,3H),0.96(d,3H),1.40(s,9H),1.60(d,3H),1.87(m,2H),2.32(t,2H),2.44(m,1H),2.66(s,3H),3.41(m,2H),3.61(s,3H),4.91(m,1H),5.30(m,1H),5.40(m,1H),7.11(br,m),7.54(d,1H),7.82(s,1H),8.08(s,1H). |
化合物 | 1H NMR(CDCl3,300MHz)数据 |
Wang240 | δ1.41(t,3H),4.43(q,2H),8.18(s,1H),8.23(s,1H),8.85(s,1H). |
Wang254 | δ1.3(t,3H),2.78(s,3H),4.34(q,2H),8.20(s,1H),8.85(s,1H). |
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PCT/CN2006/000124 WO2006097030A1 (fr) | 2005-03-18 | 2006-01-24 | Composes tandem a bis-heterocycle utiles en tant qu’agents antiviraux, leurs utilisations et compositions les comprenant |
SG2011044229A SG172716A1 (en) | 2005-03-18 | 2006-01-24 | 2-thiophen-2-yl-oxazole, 2-thiophen-2-yl-thiazole and 2-thiophen-2-yl-1h-imidazole derivatives as antiviral agents and the use thereof |
EP10003376A EP2223921B8 (en) | 2005-03-18 | 2006-01-24 | 2-Thiophen-2-yl-oxazole, 2-Thiophen-2-yl-thiazole and 2-Thiophen-2-yl-1H-imidazole derivatives as antiviral agents |
US11/886,593 US7741348B2 (en) | 2005-03-18 | 2006-01-24 | Bisheterocycle tandem compounds useful as antiviral agents, the uses thereof and the compositions comprising such compounds |
KR1020077024016A KR20070121778A (ko) | 2005-03-18 | 2006-01-24 | 항바이러스제로 유용한 텐덤 비스헤테로사이클 화합물,이의 용도 및 상기 화합물을 포함하는 조성물 |
EP06705545A EP1889843A4 (en) | 2005-03-18 | 2006-01-24 | BISHETEROCYCLUS TANDEM COMPOUNDS SUITED AS ANTIVIRAL AGENTS, APPLICATIONS THEREOF AND COMPOSITIONS CONTAINING SUCH COMPOUNDS |
KR1020117008738A KR101177692B1 (ko) | 2005-03-18 | 2006-01-24 | 항바이러스제로 유용한 텐덤 비스헤테로사이클 화합물, 이의 용도 및 상기 화합물을 포함하는 조성물 |
EP10000847A EP2218720B1 (en) | 2005-03-18 | 2006-01-24 | 2-2'-Bis-thiazole derivatives as antiviral agents |
JP2008501138A JP4939527B2 (ja) | 2005-03-18 | 2006-01-24 | 抗ウィルス剤の機能を有する両複素環連結化合物、その応用および当該化合物を含有する組成物 |
SG2011044146A SG172715A1 (en) | 2005-03-18 | 2006-01-24 | 2-2'-bis-thiazole derivatives as antiviral agents |
HK10109615.4A HK1143152A1 (en) | 2005-03-18 | 2008-07-04 | 2-thiophen-2-yl-oxazole, 2-thiophen-2-yl-thiazole and 2-thiophen-2-yl-1h- imidazole derivatives as antiviral agents |
HK10109614.5A HK1143151A1 (en) | 2005-03-18 | 2008-07-04 | 2-2'-bis-thiazole derivatives as antiviral agents |
JP2011103198A JP5314730B2 (ja) | 2005-03-18 | 2011-05-02 | 抗ウィルス剤の機能を有する両複素環連結化合物および当該化合物を含有する組成物の、ウィルス性疾患の治療における応用 |
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WO2007147336A1 (en) * | 2006-06-13 | 2007-12-27 | Shanghai Institue Of Materia Medica, Chinese Academy Of Sciences | Heterocyclic non-nucleoside compounds, their peparation, pharmaceutical composition and their use as antiviral agents |
CN102199133A (zh) * | 2010-03-24 | 2011-09-28 | 中国科学院上海药物研究所 | 2’,2-双噻唑非核苷类化合物及其制备方法、药物组合物和作为肝炎病毒抑制剂的用途 |
CN102775368A (zh) * | 2011-05-10 | 2012-11-14 | 中国科学院上海药物研究所 | 一类噻唑类化合物及其制备方法和用途 |
CN107286147A (zh) * | 2017-05-10 | 2017-10-24 | 南华大学 | N‑[5‑(1,2,4‑三唑‑1‑基)噻唑‑2‑基]吗啉基酰胺及其医药用途 |
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JP2010501567A (ja) * | 2006-08-24 | 2010-01-21 | ノバルティス アクチエンゲゼルシャフト | 代謝系、心血管系および他の障害の処置のためのステアロイル−CoA不飽和化酵素(SCD)阻害剤としての2−(ピラジン−2−イル)−チアゾールおよび2−(1H−ピラゾール−3−イル)チアゾール誘導体ならびに関連化合物 |
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-
2005
- 2005-03-18 CN CN2005100244685A patent/CN1834095B/zh active Active
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- 2006-01-24 WO PCT/CN2006/000124 patent/WO2006097030A1/zh active Application Filing
- 2006-01-24 SG SG2011044146A patent/SG172715A1/en unknown
- 2006-01-24 KR KR1020077024016A patent/KR20070121778A/ko not_active Application Discontinuation
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- 2006-01-24 JP JP2008501138A patent/JP4939527B2/ja not_active Expired - Fee Related
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Cited By (9)
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WO2007147336A1 (en) * | 2006-06-13 | 2007-12-27 | Shanghai Institue Of Materia Medica, Chinese Academy Of Sciences | Heterocyclic non-nucleoside compounds, their peparation, pharmaceutical composition and their use as antiviral agents |
CN101443330B (zh) * | 2006-06-13 | 2012-12-19 | 上海海和药物研究开发有限公司 | 杂环非核苷类化合物及其制备方法、药物组合物和作为抗病毒抑制剂的用途 |
CN102199133A (zh) * | 2010-03-24 | 2011-09-28 | 中国科学院上海药物研究所 | 2’,2-双噻唑非核苷类化合物及其制备方法、药物组合物和作为肝炎病毒抑制剂的用途 |
CN102199133B (zh) * | 2010-03-24 | 2015-08-19 | 中国科学院上海药物研究所 | 2’,2-双噻唑非核苷类化合物及其制备方法、药物组合物和作为肝炎病毒抑制剂的用途 |
CN102775368A (zh) * | 2011-05-10 | 2012-11-14 | 中国科学院上海药物研究所 | 一类噻唑类化合物及其制备方法和用途 |
CN102775368B (zh) * | 2011-05-10 | 2016-08-17 | 上海驺虞医药科技有限公司 | 一类噻唑类化合物及其制备方法和用途 |
CN107286147A (zh) * | 2017-05-10 | 2017-10-24 | 南华大学 | N‑[5‑(1,2,4‑三唑‑1‑基)噻唑‑2‑基]吗啉基酰胺及其医药用途 |
CN107286147B (zh) * | 2017-05-10 | 2021-02-12 | 南华大学 | N-[5-(1,2,4-三唑-1-基)噻唑-2-基]吗啉基酰胺及其医药用途 |
CN111848601A (zh) * | 2019-04-30 | 2020-10-30 | 南京海璞医药科技有限公司 | 一种含稠环的化合物、其应用及含其的药物组合物 |
Also Published As
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EP2223921A1 (en) | 2010-09-01 |
JP2011148833A (ja) | 2011-08-04 |
EP2218720A1 (en) | 2010-08-18 |
KR20110048592A (ko) | 2011-05-11 |
EP1889843A4 (en) | 2009-09-02 |
EP1889843A1 (en) | 2008-02-20 |
EP2223921B1 (en) | 2013-01-09 |
JP5314730B2 (ja) | 2013-10-16 |
WO2006097030A1 (fr) | 2006-09-21 |
JP4939527B2 (ja) | 2012-05-30 |
SG172716A1 (en) | 2011-07-28 |
KR20070121778A (ko) | 2007-12-27 |
KR101177692B1 (ko) | 2012-08-29 |
SG172715A1 (en) | 2011-07-28 |
JP2008533057A (ja) | 2008-08-21 |
US7741348B2 (en) | 2010-06-22 |
CN1834095B (zh) | 2011-04-20 |
EP2223921B8 (en) | 2013-02-20 |
EP2218720B1 (en) | 2013-01-09 |
US20080306121A1 (en) | 2008-12-11 |
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