Chem. J. Chinese Universities ›› 2014, Vol. 35 ›› Issue (12): 2584.doi: 10.7503/cjcu20140333
• Organic Chemistry • Previous Articles Next Articles
YANG Hongliang1, XU Guoxing1, BAO Meiying2, ZHANG Dapeng1, LI Zhiwei1,*(), PEI Yazhong1,*()
Received:
2014-04-09
Online:
2014-12-10
Published:
2014-11-06
Contact:
LI Zhiwei,PEI Yazhong
E-mail:zwl.jida@gmail.com;peiyz@jlu.edu.cn
Supported by:
CLC Number:
TrendMD:
YANG Hongliang, XU Guoxing, BAO Meiying, ZHANG Dapeng, LI Zhiwei, PEI Yazhong. Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities†[J]. Chem. J. Chinese Universities, 2014, 35(12): 2584.
Fig.1 Structures of imatinib(A) and p38 inhibitor(B) and the X-ray co-crystal structures of known allosteric kinase inhibitors(C, D) (C) Imatinib binds to Abl kinase;(D) p38 inhibitor binds to p38 kinase.
Scheme 1 Synthetic routes of intermediate 8 Reagents and conditions: a. H2, Pd/C, MeOH; b. 3,5-bis(trifluoromethyl) benzoic acid, DMAP, EDCI, DCM; c. LAH, THF, 0 ℃; d. Py·SO3, TEA, DMSO, DCM; e. NH2OH·HCl, EtOH, 70 ℃; f: (i). NCS, DMF, 0—50 ℃, (ii) N-Boc-propargylamine, TEA, DCM, 0 ℃; g. TFA, DCM, 0 ℃.
Compd. | R1 | m.p./℃ | MS, m/z [M+H+] | Compd. | R2/NR3R4 | m.p./℃ | MS, m/z [M+H+] |
---|---|---|---|---|---|---|---|
2 | — | 116—118 | 167.2 | 10b | 184—185 | 598.7 | |
3 | — | 56—58 | 406.9 | 10c | 176—178 | 614.7 | |
4 | — | 191—193 | 378.8 | 10d | 199—201 | 602.7 | |
5 | — | 227—229 | 10e | 153—155 | 652.7 | ||
6 | — | 213—215 | 391.8 | 10f | 159—161 | 614.7 | |
7 | — | 107—109 | 544.8 | 10g | 199—201 | 602.6 | |
8 | — | 125—127 | 444.8 | 10h | 91—93 | 602.7 | |
9a | 195—197 | 528.9 | 10i | 98—100 | 598.7 | ||
9b | 163—165 | 542.8 | 10j | 202—204 | 550.7 | ||
9c | 161—163 | 528.8 | 11 | — | 91—93 | 556.8 | |
9d | 130—132 | 554.8 | 12a | 121—123 | 620.7 | ||
9e | 75—77 | 590.8 | 12b | 185—186 | 627.7 | ||
9f | 96—98 | 578.7 | 12c | 106—108 | 551.7 | ||
9g | 121—123 | 598.8 | 12d | 154—156 | 659.7 | ||
10a | 201—203 | 584.7 |
Table 1 Physicochemical properties of compounds 2—12
Compd. | R1 | m.p./℃ | MS, m/z [M+H+] | Compd. | R2/NR3R4 | m.p./℃ | MS, m/z [M+H+] |
---|---|---|---|---|---|---|---|
2 | — | 116—118 | 167.2 | 10b | 184—185 | 598.7 | |
3 | — | 56—58 | 406.9 | 10c | 176—178 | 614.7 | |
4 | — | 191—193 | 378.8 | 10d | 199—201 | 602.7 | |
5 | — | 227—229 | 10e | 153—155 | 652.7 | ||
6 | — | 213—215 | 391.8 | 10f | 159—161 | 614.7 | |
7 | — | 107—109 | 544.8 | 10g | 199—201 | 602.6 | |
8 | — | 125—127 | 444.8 | 10h | 91—93 | 602.7 | |
9a | 195—197 | 528.9 | 10i | 98—100 | 598.7 | ||
9b | 163—165 | 542.8 | 10j | 202—204 | 550.7 | ||
9c | 161—163 | 528.8 | 11 | — | 91—93 | 556.8 | |
9d | 130—132 | 554.8 | 12a | 121—123 | 620.7 | ||
9e | 75—77 | 590.8 | 12b | 185—186 | 627.7 | ||
9f | 96—98 | 578.7 | 12c | 106—108 | 551.7 | ||
9g | 121—123 | 598.8 | 12d | 154—156 | 659.7 | ||
10a | 201—203 | 584.7 |
Compd. | 1H NMR(300 MHz, CDCl3), δ | 13C NMR(75 MHz, DMSO-d6), δ |
---|---|---|
2a | 8.13(d, J=3.0 Hz, 1H), 7.52(d, J=2.7 Hz, 1H), 3.90(s, 3H), 3.65(s, 2H), 2.70(s, 3H) | 167.9, 148.9, 140.3, 139.2, 124.8, 123.6, 52.0, 23.4 |
3a | 8.90(d, J=2.4 Hz, 1H), 8.74(d, J=2.1 Hz, 1H), 8.39(s, 2H), 8.30(s, 1H), 8.10(s, 1H), 3.95(s, 3H), 2.86(s, 3H) | 166.3, 163.6, 156.1, 143.6, 135.8, 132.4(q, J=34.1 Hz), 132.2 , 130.6, 127.7, 125.7, 125.3, 122.7(q, J=271.4 Hz), 52.5, 23.9 |
4b | 10.75(s, 1H), 8.76(s, 1H), 8.63(s, 2H), 8.39(s, 1H), 8.12(s, 1H), 5.40(t, J=5.1 Hz, 1H), 4.53(d, J=5.1 Hz, 2H), 2.37(s, 3H) | 162.5, 150.6, 139.0, 136.6, 135.4, 133.2, 130.5(q, J=33.2 Hz), 128.5, 125.9, 125.1, 123.1(q, J=271.4 Hz), 59.8, 20.8 |
5b | 9.15(s, 1H), 8.92(s, 1H), 8.70(s, 2H), 8.45(s, 1H), 8.42(s, 1H), 2.74(s, 3H) | 163.2, 147.3, 143.2, 135.6, 133.3, 130.6(q, J=33.3 Hz), 130.5, 129.7, 128.8, 125.8, 122.9(q, J=271.3 Hz), 17.7 |
6b | 11.63(s, 1H), 10.83(s, 1H), 8.85(s, 1H), 8.64(s, 2H), 8.48(d, J=2.1 Hz, 1H), 8.41(s, 1H), 8.35(s, 1H), 2.56(s, 3H) | 162.9, 150.9, 145.2, 141.5, 136.4, 132.9, 131.0, 130.4(q, J=33.2 Hz), 128.1, 124.6, 124.5(q, J=278.1 Hz), 21.3 |
7 | 9.00(s, 1H), 8.80(d, J=2.7 Hz, 1H), 8.43(s, 2H), 8.24(d, J=2.4 Hz, 1H), 8.04(s, 1H), 6.39(s, 1H), 5.23(t, J=5.4 Hz, 1H), 4.47(d, J=6.0 Hz, 2H), 2.61(s, 3H), 1.45(s, 9H) | 162.8, 160.9, 155.6, 151.2, 145.4, 141.9, 136.3, 133.2, 130.5(q, J=33.2 Hz), 128.5, 125.3, 124.9, 124.3(q, J=270.5 Hz), 123.5, 102.0, 78.5, 36.1, 28.1, 23.3 |
8 | 8.73(s, 1H), 8.65(s, 1H), 8.39(s, 2H), 8.29(d, J=1.8 Hz, 1H), 8.07(s, 1H), 6.41(s, 1H), 4.07(s, 3H), 2.65(s, 3H) | 175.7, 162.8, 160.8, 151.1, 142.0, 136.4, 133.4, 130.5(q, J=32.9 Hz), 128.7, 128.2, 125.3, 123.7, 123.1(q, J=271.6 Hz), 101.2, 37.8, 23.4 |
9a | 9.78(s, 1H), 8.83(s, 1H), 8.50(s, 2H), 8.27(s, 1H), 8.03(s, 1H), 6.61(s, 1H), 6.35(s, 1H), 4.57(d, J=5.4 Hz, 2H), 2.57(s, 3H), 1.24(s, 9H) | 177.8, 171.7, 162.8, 160.9, 151.3, 141.8, 136.4, 133.3, 130.6(q, J=33.2 Hz), 128.6, 128.4, 125.4, 123.7, 123.1(q, J=268.9 Hz), 101.8, 35.1, 27.3, 23.3 |
9ba | 9.13(s, 1H), 8.83(s, 1H), 8.48(s, 2H), 8.19(s, 1H), 8.07(s, 1H), 7.37(d, J=6.0 Hz, 1H), 6.37(s, 1H), 4.62(t, J=5.4 Hz, 2H), 4.40(dd, J=6.0 Hz, 1H), 4.06—3.84(m, 2H), 2.29(m, 1H), 2.11—1.82(m, 3H) | 169.3, 164.1, 158.5, 156.2, 147.8, 137.2, 131.1, 127.7, 127.2(q, J=33.7 Hz), 124.0, 123.2, 120.6, 119.1, 118.0(q, J=266.0 Hz), 97.7, 64.7, 29.8, 25.3, 20.6, 18.5 |
9ca | 9.49(s, 1H), 8.79(d, J=2.4 Hz, 1H), 8.48(s, 2H), 8.09(d, J=2.4 Hz, 1H), 8.05(s, 1H), 6.53(t, J=6.0 Hz, 1H), 6.32(s, 1H), 4.58(d, J=5.7 Hz, 2H), 2.52(s, 3H), 2.11(s, 2H), 1.14(dd, J=6.9 Hz, 1H), 1.03—0.87(m, 6H) | 173.8, 169.8, 163.9, 161.2, 152.7, 142.3, 136.1, 133.0, 132.3(q, J=33.7 Hz), 129.2, 128.3, 125.9, 124.3, 123.1(q, J=271.4 Hz), 102.8, 45.8, 35.5, 26.4, 23.4, 22.5 |
9db | 8.79(d, J=2.4 Hz, 1H), 8.66(s, 2H), 8.44(t, J=6.0 Hz, 1H), 8.35(d, J=2.4 Hz, 1H), 8.26(s, 1H), 6.64(s, 1H), 4.47(d, J=5.7 Hz, 2H), 2.56(s, 3H), 2.18(m, 1H), 1.72(s, 4H), 1.63(s, 1H), 1.33(m, 3H), 1.20(m, 2H) | 175.4, 171.1, 163.0, 161.1, 150.4, 142.6, 137.7, 135.0, 130.3(q, J=32.9 Hz), 128.5, 124.7, 123.4, 123.1(q, J=271.4 Hz), 102.0, 43.7, 34.5, 29.0, 25.4, 25.1, 23.2 |
9e | 9.04(s, 1H), 8.81(d, J=2.4 Hz, 1H), 8.47(s, 1H), 8.12(d, J=2.1 Hz, 1H), 8.07(s, 1H), 7.24—7.23(m, 1H), 7.22(s, 1H), 7.19—7.11(m, 2H), 6.25(t, J=5.7 Hz, 1H), 6.21(s, 1H), 4.55(d, J=6.0 Hz, 2H), 2.96(t, J=7.5 Hz, 2H), 2.59(s, 3H), 2.56(d, J=7.5 Hz, 2H) | 171.7, 171.1, 162.8, 160.9, 151.3, 142.0, 141.1, 136.4, 133.2, 130.6(q, J=33.3 Hz), 128.6, 128.2, 125.8, 125.4, 123.5, 123.1(q, J=271.1 Hz), 102.2, 36.7, 34.5, 30.9, 23.3 |
9f | 9.25(s, 1H), 8.85(d, J=2.4 Hz, 1H), 8.46(s, 2H), 8.03(s, 1H), 8.00(d, J=2.4 Hz, 1H), 7.32(t, J=6.0 Hz, 2H), 7.04(d, J=6.6 Hz, 1H), 6.34(s, 1H), 4.77(d, J=6.0 Hz, 2H), 3.78(s, 3H), 2.57(s, 3H) | 176.2, 171.8, 168.0, 164.4, 156.6, 147.2, 140.2, 138.4, 137.4, 135.8(q, J=33.8 Hz), 134.8, 134.7, 133.8, 133.5, 128.7, 125.4(q, J=251.4 Hz), 124.8, 122.6, 119.1, 117.7, 107.6, 60.4, 41.5, 28.6 |
9g | 9.33(s, 1H), 8.87(d, J=2.4 Hz, 1H), 8.47(s, 2H), 8.32(s, 1H), 8.02(d, J=2.4 Hz, 1H), 8.00(s, 1H), 7.91—7.77(m, 4H), 7.61—7.50(m, 2H), 7.47(t, J=5.7 Hz, 2H), 6.35(s, 1H), 4.82(d, J=5.7 Hz, 2H), 2.54(s, 3H) | 171.0, 166.5, 162.7, 161.1, 151.4, 142.0, 136.3, 134.3, 133.2, 132.1, 131.0, 130.6(q, J=33.2 Hz), 128.9, 128.5, 128.3, 128.0, 127.8, 127.7, 127.6, 126.7, 125.3, 124.1, 123.5, 123.1(q, J=271.3 Hz), 102.5, 35.4, 23.4 |
10ab | 10.93(s, 1H), 8.92(d, J=1.8 Hz, 1H), 8.65(s, 2H), 8.57(t, J=6.0 Hz, 1H), 8.43(s, 1H), 8.30(d, J=2.1 Hz, 1H), 7.99—7.83(m, 2H), 7.63—7.55(m, 3H), 6.63(s, 1H), 4.33(d, J=6.0 Hz, 2H), 2.53(s, 3H) | 169.2, 162.8, 160.7, 151.2, 141.9, 140.3, 136.3, 133.2, 132.5, 130.5(q, J=33.3 Hz), 129.1, 128.5, 128.1, 126.4, 125.3, 123.3, 123.0(q, J=271.4 Hz), 103.2, 23.2 |
10b | 8.92(s, 1H), 8.63(s, 1H), 8.43(s, 2H), 8.17(s, 1H), 8.07(s, 1H), 7.76(d, J=8.1 Hz, 2H), 7.32(d, J=8.1 Hz, 2H), 6.37(s, 1H), 4.37(d, J=6.3 Hz, 2H), 2.61(s, 3H), 2.40(s, 3H) | 169.3, 162.8, 160.8, 151.3, 142.8, 142.1, 137.6, 136.4, 133.2, 130.8(q, J=33.2 Hz), 129.6, 128.6, 128.2, 126.5, 125.3, 124.9(q, J=271.4 Hz), 123.3, 103.2, 38.0, 23.2, 20.8 |
10c | 8.93(d, J=2.1 Hz, 1H), 8.69(s, 1H), 8.41(s, 2H), 8.06(d, J=2.1 Hz, 1H), 8.04(s, 1H), 7.78(d, J=9.0 Hz, 2H), 6.95(d, J=9.0 Hz, 2H), 6.32(s, 1H), 4.32(d, J=6.3 Hz, 2H), 3.80(s, 3H), 2.57(s, 3H) | 162.8, 162.2, 160.7, 151.2, 142.0, 136.4, 133.1, 132.0, 131.4, 130.6(q, J=33.3 Hz), 128.7, 128.6, 128.2, 125.3, 123.3, 123.1(q, J=271.4 Hz), 114.2, 103.1, 55.5, 38.0, 23.2 |
10db | 10.93(s, 1H), 8.92(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.30(d, J=2.7 Hz, 1H), 7.96—7.78(m, 2H), 7.41(t, J=9.0 Hz, 2H), 6.65(s, 1H), 4.35(d, J= 3.3 Hz, 2H), 2.54(s, 3H) | 169.2, 165.8, 162.9, 162.5, 160.8, 151.3, 142.0, 136.9, 134.8(d, J=235.1 Hz), 130.6(q, J=33.2 Hz), 129.6(d, J=7.4 Hz), 128.6, 128.2, 125.5, 123.3, 123.1(q, J=271.1 Hz), 116.3(d, J=22.6 Hz), 103.3, 37.9, 23.3 |
10eb | 10.93(s, 1H), 8.91(d, J=2.4 Hz, 1H), 8.85(s, 1H), 8.65(s, 2H), 8.44(s, 1H), 8.28(d, J=2.4 Hz, 1H), 8.18—8.04(m, 2H), 8.01(d, J=8.1 Hz, 1H), 7.83(t, J=7.8 Hz, 1H), 6.66(s, 1H), 4.43(s, 2H), 2.51(s, 3H) | 168.8, 162.9, 160.8, 151.2, 142.1, 141.7, 136.4, 133.2, 130.6(q, J=30.3 Hz), 130.6(q, J=33.8 Hz), 129.3, 128.6, 128.1, 125.6, 125.5(q, J=181.2 Hz), 123.6(q, J=271.6 Hz), 123.2, 103.4, 37.8, 23.3 |
10fb | 10.92(s, 1H), 8.92(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.55(t, J=6.0 Hz, 1H), 8.42(s, 1H), 8.31(d, J=2.4 Hz, 1H), 7.49(t, J=7.8 Hz, 1H), 7.41—7.35(m, 1H), 7.33—7.28(m, 1H), 7.17(m, 1H), 6.64(s, 1H), 4.33(d, J=6.0 Hz, 2H), 3.79(s, 3H), 2.53(s, 3H) | 174.4, 168.0, 165.9, 164.5, 156.4, 147.2, 146.7, 141.5, 138.3, 135.9(q, J=33.0 Hz), 135.5, 133.7, 133.3, 130.5, 128.4, 128.2(q, J=271.6 Hz), 123.7, 123.6, 116.6, 108.4, 60.6, 43.1, 28.4 |
10gb | 10.93(s, 1H), 8.92(d, J=2.7 Hz, 1H), 8.73(t, J=6.3 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.30(d, J=2.4 Hz, 1H), 7.67—7.57(m, 3H), 7.55—7.45(m, 1H), 6.68(s, 1H), 4.38(d, J=6.0 Hz, 2H), 2.53(s, 3H) | 174.2, 168.0, 166.8(d, J=247.1 Hz), 166.0, 156.4, 147.7(d, J=6.45 Hz), 147.2, 141.6, 138.4, 136.8(d, J=7.95 Hz), 135.7(q, J=33.1 Hz), 133.8, 133.3, 130.6, 128.5, 128.2(q, J=268.9 Hz), 127.9(d, J=2.9 Hz), 125.1(d, J=20.9 Hz), 118.7(d, J=24.3 Hz), 108.6, 43.1, 28.4 |
10hb | 10.91(s, 1H), 8.91(d, J=2.4 Hz, 1H), 8.86(t, J=6.0 Hz, 1H), 8.65(s, 2H), 8.41(s, 1H), 8.28(d, J=2.4 Hz, 1H), 7.78(td, J=7.5, 1.8 Hz, 1H), 7.72—7.60(m, 1H), 7.46—7.28(m, 2H), 6.63(s, 1H), 4.43(d, J=6.3 Hz, 2H), 2.52(s, 3H) | 169.3, 163.2, 160.9, 158.4(d, J=252.2 Hz), 151.5, 142.2, 136.5, 135.8, 135.7(d, J=8.5 Hz), 133.4, 130.8(q, J=33.4 Hz), 129.8, 128.7(d, J=19.5 Hz), 128.4(d, J=9.9 Hz), 125.6, 125.2(q, J=271.0 Hz), 123.5, 123.0(d, J=3.7 Hz), 117.3(d, J=20.7 Hz), 103.5, 37.9, 23.4 |
10ib | 10.93(s, 1H), 8.92(d, J=2.1 Hz, 1H), 8.66(s, 2H), 8.42(s, 1H), 8.29(d, J=2.1 Hz, 1H), 7.83(d, J=7.2 Hz, 1H), 7.51—7.46(m, 1H), 7.41—7.27(m, 2H), 6.54(s, 1H), 4.34(d, J=6.3 Hz, 2H), 3.36(s, 3H), 2.59(s, 3H) | 169.3, 162.8, 160.7, 151.2, 142.0, 138.4, 136.6, 136.4, 134.8, 133.2, 132.9, 132.6, 132.4, 130.1(q, J=33.4 Hz), 128.5, 128.1, 126.1, 123.3, 123.1(q, J=271.3 Hz), 103.1, 37.6, 23.2, 19.7 |
10jb | 10.94(s, 1H), 8.96(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.38(d, J=2.7 Hz, 1H), 7.93(t, J=5.7 Hz, 1H), 6.85(s, 1H), 4.45(d, J=4.8 Hz, 2H), 3.22(m, 1H), 2.62(s, 3H), 1.25(s, 3H), 1.23(s, 3H) | 170.7, 162.8, 161.0, 151.3, 142.0, 136.3, 133.2, 130.6(q, J=33.3 Hz), 128.5, 128.2, 125.6, 123.4, 123.0(q, J=274.7 Hz), 103.0, 52.1, 38.0, 23.3, 16.2 |
11b | 10.90(s, 1H), 8.94(d, J=2.4 Hz, 1H), 8.64(s, 2H), 8.41(s, 1H), 8.39—8.33(m, 3H), 6.81(d, J=5.4 Hz, 1H), 6.76(s, 1H), 4.73(d, J=5.7 Hz, 2H), 2.60(s, 3H) | 162.8, 161.9, 161.0, 160.9, 154.8, 151.3, 142.0, 136.3, 133.1, 130.5(q, J=33.2 Hz), 128.5, 128.2, 125.4, 123.5, 123.0(q, J=275.6 Hz), 110.4, 102.7, 102.6, 23.3, 13.2 |
12ab | 10.94(s, 1H), 8.93(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.41(s, 1H), 8.36(d, J=2.4 Hz, 1H), 7.78(d, J=5.7 Hz, 1H), 7.72(s, 1H), 6.73(s, 1H), 5.88(d, J=5.7 Hz, 1H), 4.69(d, J=5.4 Hz, 2H), 3.62(t, J=4.5 Hz, 4H), 2.60(s, 3H), 2.32(t, J=4.8 Hz, 4H), 2.15(s, 3H) | 171.8, 162.8, 162.0, 161.0, 160.9, 155.4, 151.3, 141.9, 136.3, 133.2, 130.6(q, J=33.3 Hz), 128.6, 128.2, 125.5, 123.5, 123.1(q, J=271.8 Hz), 102.1, 54.4, 45.6, 43.1, 35.9, 23.4 |
12bb | 10.91(s, 1H), 8.95(s, 1H), 8.65(s, 2H), 8.42(s, 1H), 8.32(s, 1H), 7.71(d, J=5.7 Hz, 1H), 7.64(s, 1H), 7.28—7.20(m, 4H), 7.11(s, 1H), 6.62(s, 1H), 5.85(d, J=5.7 Hz, 1H), 4.68(d, J=4.8 Hz, 2H), 4.42(d, J=5.4 Hz, 2H), 2.58(s, 3H) | 162.7, 162.3, 161.4, 157.3, 156.0, 154.5, 151.7, 141.2, 136.3, 133.0, 130.6(q, J=32.9 Hz), 128.5, 128.0, 125.4, 123.9, 123.0(q, J=271.2 Hz), 113.1, 98.0, 43.4, 25.0, 13.0 |
12cb | 10.91(s, 1H), 8.95(d, J=2.7 Hz, 1H), 8.64(s, 2H), 8.41(s, 1H), 8.34(d, J=2.4 Hz, 1H), 7.72(d, J=5.7 Hz, 1H), 7.58(s, 1H), 6.73(s, 1H), 6.45(d, J=4.5 Hz, 1H), 5.83(d, J=5.7 Hz, 1H), 4.70(d, J=6.0 Hz, 2H), 2.72(d, J=4.8 Hz, 3H), 2.61(s, 3H) | 171.9, 162.8, 162.4, 162.2, 160.9, 155.3, 151.3, 141.9, 136.4, 133.2, 130.6(q, J=33.2 Hz), 128.6, 128.2, 125.4, 124.9(q, J=271.4 Hz), 123.6, 102.2, 35.1, 27.7, 23.4 |
12db | 11.77(s, 1H), 10.89(s, 1H), 8.94(d, J=2.7 Hz, 1H), 8.63(s, 2H), 8.40(s, 1H), 8.31(d, J=2.4 Hz, 1H), 7.86(d, J=5.4 Hz, 2H), 6.74(s, 1H), 6.19(s, 1H), 6.02(d, J=5.7 Hz, 1H), 4.77(d, J=5.4 Hz, 2H), 2.57(s, 3H), 1.21(s, 9H) | 171.7, 162.8, 162.2, 160.9, 159.0, 151.3, 142.0, 136.4, 133.2, 130.6(q, J=33.1 Hz), 128.6, 128.2, 125.4, 123.5, 123.1(q, J=267.8 Hz), 102.3, 36.0, 30.8, 30.0, 23.4 |
Table 2 Spectral data of compounds 2—12
Compd. | 1H NMR(300 MHz, CDCl3), δ | 13C NMR(75 MHz, DMSO-d6), δ |
---|---|---|
2a | 8.13(d, J=3.0 Hz, 1H), 7.52(d, J=2.7 Hz, 1H), 3.90(s, 3H), 3.65(s, 2H), 2.70(s, 3H) | 167.9, 148.9, 140.3, 139.2, 124.8, 123.6, 52.0, 23.4 |
3a | 8.90(d, J=2.4 Hz, 1H), 8.74(d, J=2.1 Hz, 1H), 8.39(s, 2H), 8.30(s, 1H), 8.10(s, 1H), 3.95(s, 3H), 2.86(s, 3H) | 166.3, 163.6, 156.1, 143.6, 135.8, 132.4(q, J=34.1 Hz), 132.2 , 130.6, 127.7, 125.7, 125.3, 122.7(q, J=271.4 Hz), 52.5, 23.9 |
4b | 10.75(s, 1H), 8.76(s, 1H), 8.63(s, 2H), 8.39(s, 1H), 8.12(s, 1H), 5.40(t, J=5.1 Hz, 1H), 4.53(d, J=5.1 Hz, 2H), 2.37(s, 3H) | 162.5, 150.6, 139.0, 136.6, 135.4, 133.2, 130.5(q, J=33.2 Hz), 128.5, 125.9, 125.1, 123.1(q, J=271.4 Hz), 59.8, 20.8 |
5b | 9.15(s, 1H), 8.92(s, 1H), 8.70(s, 2H), 8.45(s, 1H), 8.42(s, 1H), 2.74(s, 3H) | 163.2, 147.3, 143.2, 135.6, 133.3, 130.6(q, J=33.3 Hz), 130.5, 129.7, 128.8, 125.8, 122.9(q, J=271.3 Hz), 17.7 |
6b | 11.63(s, 1H), 10.83(s, 1H), 8.85(s, 1H), 8.64(s, 2H), 8.48(d, J=2.1 Hz, 1H), 8.41(s, 1H), 8.35(s, 1H), 2.56(s, 3H) | 162.9, 150.9, 145.2, 141.5, 136.4, 132.9, 131.0, 130.4(q, J=33.2 Hz), 128.1, 124.6, 124.5(q, J=278.1 Hz), 21.3 |
7 | 9.00(s, 1H), 8.80(d, J=2.7 Hz, 1H), 8.43(s, 2H), 8.24(d, J=2.4 Hz, 1H), 8.04(s, 1H), 6.39(s, 1H), 5.23(t, J=5.4 Hz, 1H), 4.47(d, J=6.0 Hz, 2H), 2.61(s, 3H), 1.45(s, 9H) | 162.8, 160.9, 155.6, 151.2, 145.4, 141.9, 136.3, 133.2, 130.5(q, J=33.2 Hz), 128.5, 125.3, 124.9, 124.3(q, J=270.5 Hz), 123.5, 102.0, 78.5, 36.1, 28.1, 23.3 |
8 | 8.73(s, 1H), 8.65(s, 1H), 8.39(s, 2H), 8.29(d, J=1.8 Hz, 1H), 8.07(s, 1H), 6.41(s, 1H), 4.07(s, 3H), 2.65(s, 3H) | 175.7, 162.8, 160.8, 151.1, 142.0, 136.4, 133.4, 130.5(q, J=32.9 Hz), 128.7, 128.2, 125.3, 123.7, 123.1(q, J=271.6 Hz), 101.2, 37.8, 23.4 |
9a | 9.78(s, 1H), 8.83(s, 1H), 8.50(s, 2H), 8.27(s, 1H), 8.03(s, 1H), 6.61(s, 1H), 6.35(s, 1H), 4.57(d, J=5.4 Hz, 2H), 2.57(s, 3H), 1.24(s, 9H) | 177.8, 171.7, 162.8, 160.9, 151.3, 141.8, 136.4, 133.3, 130.6(q, J=33.2 Hz), 128.6, 128.4, 125.4, 123.7, 123.1(q, J=268.9 Hz), 101.8, 35.1, 27.3, 23.3 |
9ba | 9.13(s, 1H), 8.83(s, 1H), 8.48(s, 2H), 8.19(s, 1H), 8.07(s, 1H), 7.37(d, J=6.0 Hz, 1H), 6.37(s, 1H), 4.62(t, J=5.4 Hz, 2H), 4.40(dd, J=6.0 Hz, 1H), 4.06—3.84(m, 2H), 2.29(m, 1H), 2.11—1.82(m, 3H) | 169.3, 164.1, 158.5, 156.2, 147.8, 137.2, 131.1, 127.7, 127.2(q, J=33.7 Hz), 124.0, 123.2, 120.6, 119.1, 118.0(q, J=266.0 Hz), 97.7, 64.7, 29.8, 25.3, 20.6, 18.5 |
9ca | 9.49(s, 1H), 8.79(d, J=2.4 Hz, 1H), 8.48(s, 2H), 8.09(d, J=2.4 Hz, 1H), 8.05(s, 1H), 6.53(t, J=6.0 Hz, 1H), 6.32(s, 1H), 4.58(d, J=5.7 Hz, 2H), 2.52(s, 3H), 2.11(s, 2H), 1.14(dd, J=6.9 Hz, 1H), 1.03—0.87(m, 6H) | 173.8, 169.8, 163.9, 161.2, 152.7, 142.3, 136.1, 133.0, 132.3(q, J=33.7 Hz), 129.2, 128.3, 125.9, 124.3, 123.1(q, J=271.4 Hz), 102.8, 45.8, 35.5, 26.4, 23.4, 22.5 |
9db | 8.79(d, J=2.4 Hz, 1H), 8.66(s, 2H), 8.44(t, J=6.0 Hz, 1H), 8.35(d, J=2.4 Hz, 1H), 8.26(s, 1H), 6.64(s, 1H), 4.47(d, J=5.7 Hz, 2H), 2.56(s, 3H), 2.18(m, 1H), 1.72(s, 4H), 1.63(s, 1H), 1.33(m, 3H), 1.20(m, 2H) | 175.4, 171.1, 163.0, 161.1, 150.4, 142.6, 137.7, 135.0, 130.3(q, J=32.9 Hz), 128.5, 124.7, 123.4, 123.1(q, J=271.4 Hz), 102.0, 43.7, 34.5, 29.0, 25.4, 25.1, 23.2 |
9e | 9.04(s, 1H), 8.81(d, J=2.4 Hz, 1H), 8.47(s, 1H), 8.12(d, J=2.1 Hz, 1H), 8.07(s, 1H), 7.24—7.23(m, 1H), 7.22(s, 1H), 7.19—7.11(m, 2H), 6.25(t, J=5.7 Hz, 1H), 6.21(s, 1H), 4.55(d, J=6.0 Hz, 2H), 2.96(t, J=7.5 Hz, 2H), 2.59(s, 3H), 2.56(d, J=7.5 Hz, 2H) | 171.7, 171.1, 162.8, 160.9, 151.3, 142.0, 141.1, 136.4, 133.2, 130.6(q, J=33.3 Hz), 128.6, 128.2, 125.8, 125.4, 123.5, 123.1(q, J=271.1 Hz), 102.2, 36.7, 34.5, 30.9, 23.3 |
9f | 9.25(s, 1H), 8.85(d, J=2.4 Hz, 1H), 8.46(s, 2H), 8.03(s, 1H), 8.00(d, J=2.4 Hz, 1H), 7.32(t, J=6.0 Hz, 2H), 7.04(d, J=6.6 Hz, 1H), 6.34(s, 1H), 4.77(d, J=6.0 Hz, 2H), 3.78(s, 3H), 2.57(s, 3H) | 176.2, 171.8, 168.0, 164.4, 156.6, 147.2, 140.2, 138.4, 137.4, 135.8(q, J=33.8 Hz), 134.8, 134.7, 133.8, 133.5, 128.7, 125.4(q, J=251.4 Hz), 124.8, 122.6, 119.1, 117.7, 107.6, 60.4, 41.5, 28.6 |
9g | 9.33(s, 1H), 8.87(d, J=2.4 Hz, 1H), 8.47(s, 2H), 8.32(s, 1H), 8.02(d, J=2.4 Hz, 1H), 8.00(s, 1H), 7.91—7.77(m, 4H), 7.61—7.50(m, 2H), 7.47(t, J=5.7 Hz, 2H), 6.35(s, 1H), 4.82(d, J=5.7 Hz, 2H), 2.54(s, 3H) | 171.0, 166.5, 162.7, 161.1, 151.4, 142.0, 136.3, 134.3, 133.2, 132.1, 131.0, 130.6(q, J=33.2 Hz), 128.9, 128.5, 128.3, 128.0, 127.8, 127.7, 127.6, 126.7, 125.3, 124.1, 123.5, 123.1(q, J=271.3 Hz), 102.5, 35.4, 23.4 |
10ab | 10.93(s, 1H), 8.92(d, J=1.8 Hz, 1H), 8.65(s, 2H), 8.57(t, J=6.0 Hz, 1H), 8.43(s, 1H), 8.30(d, J=2.1 Hz, 1H), 7.99—7.83(m, 2H), 7.63—7.55(m, 3H), 6.63(s, 1H), 4.33(d, J=6.0 Hz, 2H), 2.53(s, 3H) | 169.2, 162.8, 160.7, 151.2, 141.9, 140.3, 136.3, 133.2, 132.5, 130.5(q, J=33.3 Hz), 129.1, 128.5, 128.1, 126.4, 125.3, 123.3, 123.0(q, J=271.4 Hz), 103.2, 23.2 |
10b | 8.92(s, 1H), 8.63(s, 1H), 8.43(s, 2H), 8.17(s, 1H), 8.07(s, 1H), 7.76(d, J=8.1 Hz, 2H), 7.32(d, J=8.1 Hz, 2H), 6.37(s, 1H), 4.37(d, J=6.3 Hz, 2H), 2.61(s, 3H), 2.40(s, 3H) | 169.3, 162.8, 160.8, 151.3, 142.8, 142.1, 137.6, 136.4, 133.2, 130.8(q, J=33.2 Hz), 129.6, 128.6, 128.2, 126.5, 125.3, 124.9(q, J=271.4 Hz), 123.3, 103.2, 38.0, 23.2, 20.8 |
10c | 8.93(d, J=2.1 Hz, 1H), 8.69(s, 1H), 8.41(s, 2H), 8.06(d, J=2.1 Hz, 1H), 8.04(s, 1H), 7.78(d, J=9.0 Hz, 2H), 6.95(d, J=9.0 Hz, 2H), 6.32(s, 1H), 4.32(d, J=6.3 Hz, 2H), 3.80(s, 3H), 2.57(s, 3H) | 162.8, 162.2, 160.7, 151.2, 142.0, 136.4, 133.1, 132.0, 131.4, 130.6(q, J=33.3 Hz), 128.7, 128.6, 128.2, 125.3, 123.3, 123.1(q, J=271.4 Hz), 114.2, 103.1, 55.5, 38.0, 23.2 |
10db | 10.93(s, 1H), 8.92(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.30(d, J=2.7 Hz, 1H), 7.96—7.78(m, 2H), 7.41(t, J=9.0 Hz, 2H), 6.65(s, 1H), 4.35(d, J= 3.3 Hz, 2H), 2.54(s, 3H) | 169.2, 165.8, 162.9, 162.5, 160.8, 151.3, 142.0, 136.9, 134.8(d, J=235.1 Hz), 130.6(q, J=33.2 Hz), 129.6(d, J=7.4 Hz), 128.6, 128.2, 125.5, 123.3, 123.1(q, J=271.1 Hz), 116.3(d, J=22.6 Hz), 103.3, 37.9, 23.3 |
10eb | 10.93(s, 1H), 8.91(d, J=2.4 Hz, 1H), 8.85(s, 1H), 8.65(s, 2H), 8.44(s, 1H), 8.28(d, J=2.4 Hz, 1H), 8.18—8.04(m, 2H), 8.01(d, J=8.1 Hz, 1H), 7.83(t, J=7.8 Hz, 1H), 6.66(s, 1H), 4.43(s, 2H), 2.51(s, 3H) | 168.8, 162.9, 160.8, 151.2, 142.1, 141.7, 136.4, 133.2, 130.6(q, J=30.3 Hz), 130.6(q, J=33.8 Hz), 129.3, 128.6, 128.1, 125.6, 125.5(q, J=181.2 Hz), 123.6(q, J=271.6 Hz), 123.2, 103.4, 37.8, 23.3 |
10fb | 10.92(s, 1H), 8.92(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.55(t, J=6.0 Hz, 1H), 8.42(s, 1H), 8.31(d, J=2.4 Hz, 1H), 7.49(t, J=7.8 Hz, 1H), 7.41—7.35(m, 1H), 7.33—7.28(m, 1H), 7.17(m, 1H), 6.64(s, 1H), 4.33(d, J=6.0 Hz, 2H), 3.79(s, 3H), 2.53(s, 3H) | 174.4, 168.0, 165.9, 164.5, 156.4, 147.2, 146.7, 141.5, 138.3, 135.9(q, J=33.0 Hz), 135.5, 133.7, 133.3, 130.5, 128.4, 128.2(q, J=271.6 Hz), 123.7, 123.6, 116.6, 108.4, 60.6, 43.1, 28.4 |
10gb | 10.93(s, 1H), 8.92(d, J=2.7 Hz, 1H), 8.73(t, J=6.3 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.30(d, J=2.4 Hz, 1H), 7.67—7.57(m, 3H), 7.55—7.45(m, 1H), 6.68(s, 1H), 4.38(d, J=6.0 Hz, 2H), 2.53(s, 3H) | 174.2, 168.0, 166.8(d, J=247.1 Hz), 166.0, 156.4, 147.7(d, J=6.45 Hz), 147.2, 141.6, 138.4, 136.8(d, J=7.95 Hz), 135.7(q, J=33.1 Hz), 133.8, 133.3, 130.6, 128.5, 128.2(q, J=268.9 Hz), 127.9(d, J=2.9 Hz), 125.1(d, J=20.9 Hz), 118.7(d, J=24.3 Hz), 108.6, 43.1, 28.4 |
10hb | 10.91(s, 1H), 8.91(d, J=2.4 Hz, 1H), 8.86(t, J=6.0 Hz, 1H), 8.65(s, 2H), 8.41(s, 1H), 8.28(d, J=2.4 Hz, 1H), 7.78(td, J=7.5, 1.8 Hz, 1H), 7.72—7.60(m, 1H), 7.46—7.28(m, 2H), 6.63(s, 1H), 4.43(d, J=6.3 Hz, 2H), 2.52(s, 3H) | 169.3, 163.2, 160.9, 158.4(d, J=252.2 Hz), 151.5, 142.2, 136.5, 135.8, 135.7(d, J=8.5 Hz), 133.4, 130.8(q, J=33.4 Hz), 129.8, 128.7(d, J=19.5 Hz), 128.4(d, J=9.9 Hz), 125.6, 125.2(q, J=271.0 Hz), 123.5, 123.0(d, J=3.7 Hz), 117.3(d, J=20.7 Hz), 103.5, 37.9, 23.4 |
10ib | 10.93(s, 1H), 8.92(d, J=2.1 Hz, 1H), 8.66(s, 2H), 8.42(s, 1H), 8.29(d, J=2.1 Hz, 1H), 7.83(d, J=7.2 Hz, 1H), 7.51—7.46(m, 1H), 7.41—7.27(m, 2H), 6.54(s, 1H), 4.34(d, J=6.3 Hz, 2H), 3.36(s, 3H), 2.59(s, 3H) | 169.3, 162.8, 160.7, 151.2, 142.0, 138.4, 136.6, 136.4, 134.8, 133.2, 132.9, 132.6, 132.4, 130.1(q, J=33.4 Hz), 128.5, 128.1, 126.1, 123.3, 123.1(q, J=271.3 Hz), 103.1, 37.6, 23.2, 19.7 |
10jb | 10.94(s, 1H), 8.96(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.43(s, 1H), 8.38(d, J=2.7 Hz, 1H), 7.93(t, J=5.7 Hz, 1H), 6.85(s, 1H), 4.45(d, J=4.8 Hz, 2H), 3.22(m, 1H), 2.62(s, 3H), 1.25(s, 3H), 1.23(s, 3H) | 170.7, 162.8, 161.0, 151.3, 142.0, 136.3, 133.2, 130.6(q, J=33.3 Hz), 128.5, 128.2, 125.6, 123.4, 123.0(q, J=274.7 Hz), 103.0, 52.1, 38.0, 23.3, 16.2 |
11b | 10.90(s, 1H), 8.94(d, J=2.4 Hz, 1H), 8.64(s, 2H), 8.41(s, 1H), 8.39—8.33(m, 3H), 6.81(d, J=5.4 Hz, 1H), 6.76(s, 1H), 4.73(d, J=5.7 Hz, 2H), 2.60(s, 3H) | 162.8, 161.9, 161.0, 160.9, 154.8, 151.3, 142.0, 136.3, 133.1, 130.5(q, J=33.2 Hz), 128.5, 128.2, 125.4, 123.5, 123.0(q, J=275.6 Hz), 110.4, 102.7, 102.6, 23.3, 13.2 |
12ab | 10.94(s, 1H), 8.93(d, J=2.4 Hz, 1H), 8.65(s, 2H), 8.41(s, 1H), 8.36(d, J=2.4 Hz, 1H), 7.78(d, J=5.7 Hz, 1H), 7.72(s, 1H), 6.73(s, 1H), 5.88(d, J=5.7 Hz, 1H), 4.69(d, J=5.4 Hz, 2H), 3.62(t, J=4.5 Hz, 4H), 2.60(s, 3H), 2.32(t, J=4.8 Hz, 4H), 2.15(s, 3H) | 171.8, 162.8, 162.0, 161.0, 160.9, 155.4, 151.3, 141.9, 136.3, 133.2, 130.6(q, J=33.3 Hz), 128.6, 128.2, 125.5, 123.5, 123.1(q, J=271.8 Hz), 102.1, 54.4, 45.6, 43.1, 35.9, 23.4 |
12bb | 10.91(s, 1H), 8.95(s, 1H), 8.65(s, 2H), 8.42(s, 1H), 8.32(s, 1H), 7.71(d, J=5.7 Hz, 1H), 7.64(s, 1H), 7.28—7.20(m, 4H), 7.11(s, 1H), 6.62(s, 1H), 5.85(d, J=5.7 Hz, 1H), 4.68(d, J=4.8 Hz, 2H), 4.42(d, J=5.4 Hz, 2H), 2.58(s, 3H) | 162.7, 162.3, 161.4, 157.3, 156.0, 154.5, 151.7, 141.2, 136.3, 133.0, 130.6(q, J=32.9 Hz), 128.5, 128.0, 125.4, 123.9, 123.0(q, J=271.2 Hz), 113.1, 98.0, 43.4, 25.0, 13.0 |
12cb | 10.91(s, 1H), 8.95(d, J=2.7 Hz, 1H), 8.64(s, 2H), 8.41(s, 1H), 8.34(d, J=2.4 Hz, 1H), 7.72(d, J=5.7 Hz, 1H), 7.58(s, 1H), 6.73(s, 1H), 6.45(d, J=4.5 Hz, 1H), 5.83(d, J=5.7 Hz, 1H), 4.70(d, J=6.0 Hz, 2H), 2.72(d, J=4.8 Hz, 3H), 2.61(s, 3H) | 171.9, 162.8, 162.4, 162.2, 160.9, 155.3, 151.3, 141.9, 136.4, 133.2, 130.6(q, J=33.2 Hz), 128.6, 128.2, 125.4, 124.9(q, J=271.4 Hz), 123.6, 102.2, 35.1, 27.7, 23.4 |
12db | 11.77(s, 1H), 10.89(s, 1H), 8.94(d, J=2.7 Hz, 1H), 8.63(s, 2H), 8.40(s, 1H), 8.31(d, J=2.4 Hz, 1H), 7.86(d, J=5.4 Hz, 2H), 6.74(s, 1H), 6.19(s, 1H), 6.02(d, J=5.7 Hz, 1H), 4.77(d, J=5.4 Hz, 2H), 2.57(s, 3H), 1.21(s, 9H) | 171.7, 162.8, 162.2, 160.9, 159.0, 151.3, 142.0, 136.4, 133.2, 130.6(q, J=33.1 Hz), 128.6, 128.2, 125.4, 123.5, 123.1(q, J=267.8 Hz), 102.3, 36.0, 30.8, 30.0, 23.4 |
Compd. | Inhibition*(%) | IC50/(μmol·L-1) | Compd. | Inhibition*(%) | IC50/(μmol·L-1) |
---|---|---|---|---|---|
9a | 15.5 | 10e | 17.3 | ||
9b | 9.7 | 10f | 10.0 | ||
9c | 22.5 | 10g | 51.8 | 8.5 | |
9d | 24.1 | 10h | 56.7 | 13.4 | |
9e | 16.1 | 10i | 72.2 | 6.7 | |
9f | 20.6 | 10j | 12.8 | ||
9g | 28.3 | 12a | 65.0 | 15.6 | |
10a | 59.8 | 9.4 | 12b | 100.0 | 7.3 |
10b | 20.4 | 12c | 63.0 | 15.2 | |
10c | 21.9 | 12d | 82.0 | 11.3 | |
10d | 47.2 | INK128 | 0.36 |
Table 3 Anti-tumor activities against human breast cancer cell line(MCF-7)
Compd. | Inhibition*(%) | IC50/(μmol·L-1) | Compd. | Inhibition*(%) | IC50/(μmol·L-1) |
---|---|---|---|---|---|
9a | 15.5 | 10e | 17.3 | ||
9b | 9.7 | 10f | 10.0 | ||
9c | 22.5 | 10g | 51.8 | 8.5 | |
9d | 24.1 | 10h | 56.7 | 13.4 | |
9e | 16.1 | 10i | 72.2 | 6.7 | |
9f | 20.6 | 10j | 12.8 | ||
9g | 28.3 | 12a | 65.0 | 15.6 | |
10a | 59.8 | 9.4 | 12b | 100.0 | 7.3 |
10b | 20.4 | 12c | 63.0 | 15.2 | |
10c | 21.9 | 12d | 82.0 | 11.3 | |
10d | 47.2 | INK128 | 0.36 |
[1] | Zhang J. M., Yang P. L., Gray N. S., Nat. Rev. Cancer, 2009, 9, 28—39 |
[2] | Philip C., Nat. Rev. Drug Discov., 2002, 1, 309—315 |
[3] | Liu D., Zhu X. J., Jiang M., Chen H., Lan S. P., Chem. J. Chinese Universities, 2012, 33(10), 2249—2255 |
(刘丹, 朱秀杰, 姜梦, 陈虹, 兰帅鹏. 高等学校化学学报, 2012, 33(10), 2249—2255) | |
[4] | Lu H. B., Wang S. H., Li Q. M., Wang Y. S., Chem. Res. Chinese Universities, 2013, 29(1), 67—70 |
[5] | Sun X. X., Sun T., Wang T. Y., Zhang Y., Liu H. J., Wang Q., Niu G. J., Liu W., Zhou H. G., Yang C., Chem. Res. Chinese Universities, 2013, 29(6), 1098—1103 |
[6] | Zhang C., Bollag G., Curr. Opin. Genet. Dev., 2010, 20, 79—86 |
[7] | Pargellis C., Tong L., Churchill L., Cirillo P. F., Gilmore T., Graham A. G., Grob P. M., Hickey E. R., Moss N., Pav S., Regan J., Nat. Struct. Biol., 2002, 9, 268—272 |
[8] | Yang H. L., Chen T., Bai X., Pei Y. Z., J. Chin. Pharma. Sci., 2012, 21, 531—543 |
[9] | Liu Y., Gray N. S., Nat. Chem. Biol., 2006, 2, 358—364 |
[10] | Fang Z.Z., Grütter G., Rauh D., ACS Chem. Biol., 2012, 8(1), 58—70 |
[11] | Vandana L., Indraneel G., Current Pharm. Design, 2012, 18, 2936—2945 |
[12] | Dietrich J., Hulme C., Hurley L. H., Bioorg. Med. Chem., 2010, 18, 5738—5748 |
[13] | Nagar B., Bornmann W. G., Pellicena P., Schindler T., Veach D. R., Miller W. T., Clarkson B., Kuriyan J., Cancer Res., 2002, 62, 4236—4243 |
[14] | Liu C. J., Lin J., Wrobleski S. T., Lin S. Q., Hynes J. J., Wu H., Dyckman A. J., Li T. L., Wityak J., Gillooly K. M., Pitt S., Shen D. R., Zhang R. F., McIntyre K. W., Salter-Cid L., Shuster D. J., Zhang H. J., Marathe P. H., Doweyko A. M., Sack J. S., Kiefer S. E., Kish K. F., Newitt J. A., McKinnon M., Dodd J. H., Barrish J. C., Schieven G. L., Leftheris K., J. Med. Chem., 2010, 53, 6629—6639 |
[15] | Stockmann V., Bakke J. M., Bruheim P., Fiksdahl A., Tetrahedron,2009, 65, 3668—3672 |
[16] | Yapi A. D., Desbois N., Chezal J. M., Chavignon O., Teulade J. C., Valentin A., Blache Y., Eur. J. Med. Chem., 2010, 45, 2854—2859 |
[17] | Tanis S. P., Parker T. T., Colca J. R., Fisher R. M., Kletzein R. F., J. Med. Chem., 1996, 39, 5053—5063 |
[18] | Parikh J. R., Doering W. V. E., J. Am. Chem. Soc., 1967, 89, 5505—5507 |
[19] | Yano J. K., Denton T. T., Cerny M. A., Zhang X. D., Johnson E. F., Cashman J. R., J. Med. Chem., 2006, 49, 6987—7001 |
[20] | Kamal A., Dastagiri D., Ramaiah M. J., Reddy J. S., Bharathi E. V., Reddy M. K., Sagar M. V. P., Reddy T. L., Pushpavalli S. N. C. V. L., Pal-Bhadra M., Eur. J. Med. Chem., 2011, 46, 5817—5824 |
[21] | Altmann E., Aichholz R., Betschart C., Buhl T., Green J., Irie O., Teno N., Lattmann R., Tintelnot-Blomley M., Missbach M., J. Med. Chem., 2002, 50, 591—594 |
[22] | Zhang X. Q., Hufnagel H., Hou C. F., Opas E., McKenney S., Crysler C., O’Neill J., Johnson D., Sui Z. H., Bioorg. Med. Chem. Lett., 2011, 21, 6042—6048 |
[23] | Choi H. G., Ren P. D., Adrian F., Sun F. X., Lee H. S., Wang X., Ding Q., Zhang G. B., Xie Y. P., Zhang J. M., Liu Y., Tuntland T., Warmuth M., Manley P. W., Mestan J., Gray N. S., Sim T., J. Med. Chem., 2010, 53, 5439—5448 |
[24] | Bogoyevitch M. A., Fairlie D. P., Drug Discov. Today, 2007, 12, 622—633 |
[25] | Badrinarayan P., Sastry G. N., J. Mol. Graphics Modell., 2012, 34, 89—100 |
[1] | XIAO Yanhua, ZHANG Guangjie, ZONG Liang, LIU Guohong, REN Lijun, DONG Junxing. Chemical Constituents and Antitumor Activity of Tupistra chinensis † [J]. Chem. J. Chinese Universities, 2019, 40(9): 1897. |
[2] | LÜ Mingjun,LI Wen,YANG Xinying,FANG Hao. Synthesis and Antitumor Activity of N9 Position Aromatic Substituted Purine-8-one Derivatives† [J]. Chem. J. Chinese Universities, 2019, 40(2): 254. |
[3] | FANG Fang,XUE Liangmin,CONG Jing,TIAN Chao,WANG Xiaowei,LIU Junyi,ZHANG Zhili. Synthesis and Anti-tumor Activity Evaluation of a Series of 2- or 4-Substituted Pyrido[3,2-d]pyrimidines as Nonclassical Antifolates [J]. Chem. J. Chinese Universities, 2019, 40(10): 2111. |
[4] | ZHANG Peiquan,YANG Qianqian,LONG Huidan,CHEN Xin. Synthesis and Antitumor Activity of Auranofin Derivatives [J]. Chem. J. Chinese Universities, 2019, 40(10): 2097. |
[5] | BAI Xinfa, MA Xuan, XIE Xiaoxia, SHAO Mingsha, GUO Ningning, YAN Ning, YAO Lei. Synthesis and Anti-tumor Activity of Tubulysins Analogues† [J]. Chem. J. Chinese Universities, 2017, 38(1): 47. |
[6] | GUO Liang, CAO Rihui, FAN Wenxi, GAN Ziyun, MA Qin. Design, Synthesis and in vitro Antitumor Activities of Novel Bivalent β-Carbolines† [J]. Chem. J. Chinese Universities, 2016, 37(6): 1093. |
[7] | ZHANG Jie, ZHOU Changjian, XIE Jianwei, DAI Bin. Synthesis and Antitumor Activities of Rhein-Valine Adducts† [J]. Chem. J. Chinese Universities, 2016, 37(12): 2159. |
[8] | ZHOU Hao, DUAN Zhigang, ZHAO Shuang, BAO Meiying, LI Zhiwei, PEI Yazhong. Design and Synthesis of Phenylpyrimidine and Their Anticancer Activity† [J]. Chem. J. Chinese Universities, 2015, 36(9): 1694. |
[9] | WANG Gang, HAN Leiqiang, FANG Hao. Syntheses and Antitumor Activities of Phenylpiperazine Derivatives† [J]. Chem. J. Chinese Universities, 2015, 36(12): 2435. |
[10] | GUO Hua, YANG Chengling, WANG Wei, LAI Quanyong, YUAN Zhi. Preparation of Liver-targeted Nano-prodrug Based on Sodium Alginate Derivative and the Study on Antitumor Activity† [J]. Chem. J. Chinese Universities, 2014, 35(8): 1835. |
[11] | SONG Xiudao, HE Jun, MA Jin, LIU Yunmei, ZHENG Xing, LEI Xiaoyong, GUO Yu. Syntheses and Anticancer Activities of Glycine Derivatives of Chrysin† [J]. Chem. J. Chinese Universities, 2014, 35(7): 1465. |
[12] | WANG Junhua, WANG Quande, DUN Yanyan, FANG Hao. Syntheses and Antitumor Activities of Purine-sulfonamides Derivatives† [J]. Chem. J. Chinese Universities, 2014, 35(6): 1189. |
[13] | YANG Haikui, XU Wanfu, DUAN Anna, YOU Wenwei, ZHAO Peiliang. Syntheses and Biological Activities of Novel Imine and Imide Derivatives Bearing 1,2,4-Triazole Moiety† [J]. Chem. J. Chinese Universities, 2014, 35(3): 555. |
[14] | GUO Liang, CAO Rihui, FAN Wenxi, MA Qin. Synthesis and Biological Evaluation of 1,2,7,9-Tetrasubstituted Harmine Derivatives as Potential Antitumor Agents† [J]. Chem. J. Chinese Universities, 2014, 35(3): 518. |
[15] | DING Guobin, LI Binchun, GUO Yi, XU Li. Spectral Properties and Antitumor Activity of 10-Hydroxycamptothecin and Its Application in Cell Labeling† [J]. Chem. J. Chinese Universities, 2014, 35(11): 2324. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||