高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (12): 2502.doi: 10.7503/cjcu20190544
李艳杰1,2,王恩思1,邵晓玮1,张兴民3,牛生秀1,杨丽娟1,武毅1,*()
收稿日期:
2019-10-21
出版日期:
2019-12-04
发布日期:
2019-12-04
通讯作者:
武毅
E-mail:wuyi@jlu.edu.cn
基金资助:
Yanjie LI1,2,Ensi WANG1,Xiaowei SHAO1,Xingmin ZHANG3,Shengxiu NIU1,Lijuan YANG1,Yi WU1,*()
Received:
2019-10-21
Online:
2019-12-04
Published:
2019-12-04
Contact:
Yi WU
E-mail:wuyi@jlu.edu.cn
Supported by:
摘要:
为了合成含有咪唑并喹啉结构骨架的高效PI3K/mTOR抑制剂, 以4-氯喹啉与苯胺的芳香亲核取代(SNAr)反应、 芳香二胺与三光气Traube缩合反应以及双芳基的Suzuki交叉偶联反应等为关键步骤, 合成了15个结构新颖的咪唑酮并[4,5-c]喹啉衍生物(8Aa~8Ae, 8Ba~8Be和8Ca~8Ce). 经核磁共振波谱(NMR)和高分辨质谱(HRMS)分析确证了关键中间体和目标化合物的结构. 采用ADP-Glo激酶试剂盒和TR-FRET mTOR试剂盒法检测了目标化合物对PI3K/mTOR的体外抑制活性, 发现所有化合物均表现出较强的活性.
中图分类号:
TrendMD:
李艳杰,王恩思,邵晓玮,张兴民,牛生秀,杨丽娟,武毅. 咪唑酮并[4,5-c]喹啉衍生物的合成及体外生物活性. 高等学校化学学报, 2019, 40(12): 2502.
Yanjie LI,Ensi WANG,Xiaowei SHAO,Xingmin ZHANG,Shengxiu NIU,Lijuan YANG,Yi WU. Synthesis and Biological Activity in vitro of Imidazo[4,5-c]quinoline Derivatives †. Chem. J. Chinese Universities, 2019, 40(12): 2502.
Compd. | m. p./℃ | Compd. | m. p./℃ | Compd. | m. p./℃ |
---|---|---|---|---|---|
2A | 133—134 | 4A | 214—217 | 6A | 219—221 |
2B | 140—142 | 4B | 210—213 | 6B | 213—215 |
2C | 138—141 | 4C | 192—195 | 6C | 215—217 |
3A | 166—168 | 5A | 230—232 | 7A | 196—198 |
3B | 169—170 | 5B | 225—227 | 7B | 186—188 |
3C | 174—177 | 5C | 224—226 | 7C | 227—230 |
Table 1 Melting points of compounds 2—7
Compd. | m. p./℃ | Compd. | m. p./℃ | Compd. | m. p./℃ |
---|---|---|---|---|---|
2A | 133—134 | 4A | 214—217 | 6A | 219—221 |
2B | 140—142 | 4B | 210—213 | 6B | 213—215 |
2C | 138—141 | 4C | 192—195 | 6C | 215—217 |
3A | 166—168 | 5A | 230—232 | 7A | 196—198 |
3B | 169—170 | 5B | 225—227 | 7B | 186—188 |
3C | 174—177 | 5C | 224—226 | 7C | 227—230 |
Compd. | Appearance | Yield(%) | m. p./℃ | HRMS(calcd.), m/z[M+1]+ |
---|---|---|---|---|
8Aa | White solid | 73 | 275—277 | 528.2321(528.2340) |
8Ab | White solid | 78 | 289—292 | 564.1991(564.1984) |
8Ac | White solid | 56 | 284—286 | 581.2335(581.2349) |
8Ad | White solid | 92 | 263—267 | 544.2270(544.2280) |
8Ae | White solid | 92 | 235—239 | 558.2427(558.2435) |
8Ba | White solid | 73 | 277—279 | 526.2165(526.2181) |
8Bb | White solid | 77 | 279—282 | 562.1835(562.1862) |
8Bc | White solid | 56 | 278—280 | 579.2179(579.2197) |
8Bd | White solid | 87 | 268—270 | 542.2114(542.2137) |
8Be | White solid | 65 | 235—238 | 556.2270(556.2288) |
8Ca | White solid | 65 | 281—283 | 552.2321(552.2345) |
8Cb | White solid | 61 | 286—288 | 588.1991(588.2014) |
8Cc | White solid | 60 | 283—285 | 605.2335(605.2361) |
8Cd | White solid | 89 | 279—281 | 568.2270(568.2294) |
8Ce | White solid | 47 | 279—281 | 582.2427(582.2451) |
Table 2 Appearance, yields, melting points and HRMS data of compounds 8
Compd. | Appearance | Yield(%) | m. p./℃ | HRMS(calcd.), m/z[M+1]+ |
---|---|---|---|---|
8Aa | White solid | 73 | 275—277 | 528.2321(528.2340) |
8Ab | White solid | 78 | 289—292 | 564.1991(564.1984) |
8Ac | White solid | 56 | 284—286 | 581.2335(581.2349) |
8Ad | White solid | 92 | 263—267 | 544.2270(544.2280) |
8Ae | White solid | 92 | 235—239 | 558.2427(558.2435) |
8Ba | White solid | 73 | 277—279 | 526.2165(526.2181) |
8Bb | White solid | 77 | 279—282 | 562.1835(562.1862) |
8Bc | White solid | 56 | 278—280 | 579.2179(579.2197) |
8Bd | White solid | 87 | 268—270 | 542.2114(542.2137) |
8Be | White solid | 65 | 235—238 | 556.2270(556.2288) |
8Ca | White solid | 65 | 281—283 | 552.2321(552.2345) |
8Cb | White solid | 61 | 286—288 | 588.1991(588.2014) |
8Cc | White solid | 60 | 283—285 | 605.2335(605.2361) |
8Cd | White solid | 89 | 279—281 | 568.2270(568.2294) |
8Ce | White solid | 47 | 279—281 | 582.2427(582.2451) |
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
---|---|
2A | 10.68(s, 1H), 9.44(s, 1H), 7.84(d, J=8.8 Hz, 1H), 7.73—7.71(m, 1H), 7.60(s, 1H), 7.38—7.33(m, 5H), 7.25(d, J=8.4 Hz, 2H), 7.11(d, J=8.4 Hz, 2H), 5.29(s, 1H), 5.16(s, 2H), 4.36(s, 2H), 2.91(s, 2H), 2.78—2.71(m, 1H), 1.88(d, J=12.0 Hz, 2H), 1.66(d, J=10.8 Hz, 2H) |
2B | 10.45(s, 1H), 9.31(s, 1H), 7.76(d, J=8.0 Hz, 1H), 7.69(s, 1H), 7.63(d, J=8.4 Hz, 1H), 7.32—7.25(m, 7H), 7.04(d, J=7.4 Hz, 2H), 6.02(s, 1H), 5.12(s, 2H), 4.12(s, 2H), 3.68(s, 2H), 2.49(s, 2H) |
2C | 10.52(s, 1H), 9.44(s, 1H), 7.86(d, J=8.8 Hz, 1H), 7.78—7.74(m, 2H), 7.37(s, 5H), 7.34(s, 2H), 7.07(d, J=8.0 Hz, 2H), 6.47(s, 1H), 5.19—5.12(m, 2H), 4.63(s, 2H), 3.17—3.05(m, 1H), 2.26(d, J=16.8 Hz, 2H), 2.04(s, 2H), 1.78—1.68(m, 1H) |
3A | 8.56(s, 1H), 7.95(s, 1H), 7.85(d, J=8.2 Hz, 1H), 7.48(d, J=8.4 Hz, 1H), 7.37—7.26(m, 5H), 7.03(d, J=8.2 Hz, 2H), 6.60(d, J=8.2 Hz, 2H), 6.08(s, 1H), 5.16(s, 2H), 4.30(s, 2H), 4.13(s, 2H), 2.84(s, 2H), 2.56(t, J=11.9 Hz, 1H), 1.78(d, J=12.4 Hz, 2H), 1.61—1.51(m, 2H) |
3B | 8.55(s, 1H), 7.92(d, J=2.0 Hz, 1H), 7.82(d, J=8.8 Hz, 1H), 7.47(dd, J=2.0, 8.8 Hz, 1H), 7.36—7.29(m, 5H), 7.20(d, J=8.8 Hz, 2H), 6.58(d, J=8.8 Hz, 2H), 6.01(s, 1H), 5.87(s, 1H), 5.16(s, 2H), 4.11(s, 4H), 3.67(t, J=5.6 Hz, 2H), 2.46(s, 2H) |
3C | 8.55(s, 1H), 7.94(s, 1H), 7.82(d, J=8.9 Hz, 1H), 7.48—7.46(m, 1H), 7.32—7.26(m, 5H), 7.17(d, J=7.6 Hz, 2H), 6.56(d, J=8.3 Hz, 2H), 6.29—6.21(m, 2H), 5.13(d, J=12.9 Hz, 2H), 4.58(s, 2H), 4.16(s, 2H), 3.11—2.96(m, 1H), 2.16(d, J=9.4 Hz, 2H), 1.94(d, J=8.0 Hz, 2H), 1.68(s, 1H) |
4A | 11.87(s, 1H), 9.03(s, 1H), 8.15(d, J=9.2 Hz, 1H), 7.85—7.80(m, 5H), 7.64—7.59(m, 4H), 7.28(s, 1H), 5.85(s, 2H), 5.37(s, 2H), 4.49(d, J=13.2 Hz, 2H), 3.18—3.12(m, 3H), 2.14(d, J=12.3 Hz, 2H), 1.92(s, 1H) |
4B | 9.09(s, 1H), 8.55(s, 1H), 7.92(d, J=2.4 Hz, 1H), 7.82(d, J=9.2 Hz, 1H), 7.47(dd, J=2.4, 9.2 Hz, 1H), 7.36—7.29(m, 5H), 7.25(d, J=8.4 Hz, 2H), 6.64(d, J=8.4 Hz, 2H), 6.04(s, 1H), 5.38(s, 2H), 3.93(s, 2H), 3.64(t, J=5.6 Hz, 2H), 2.90(s, 2H) |
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
4C | 8.14(t, J=7.5 Hz, 2H), 7.93(s, 2H), 7.83(d, J=8.8 Hz, 3H), 7.58(s, 2H), 7.52(t, J=7.3 Hz, 2H), 7.49(s, 2H), 6.97(d, J=5.1 Hz, 1H), 4.81—4.74(m, 2H), 3.70(s, 1H), 3.31(s, 1H), 3.07(s, 1H), 2.90(s, 1H), 2.63(d, J=13.2 Hz, 1H), 2.41(s, 1H), 2.21(s, 2H), 2.01(s, 1H) |
5A | 8.88(s, 1H), 8.08(d, J=9.0 Hz, 1H), 7.70(d, J=17.8 Hz, 1H), 7.61(d, J=8.2 Hz, 4H), 7.56—7.45(m, 6H), 5.31(s, 2H), 4.53(s, 2H), 3.78(s, 3H), 3.08(s, 2H), 3.01(t, J=12.2 Hz, 1H), 2.11(d, J=11.4 Hz, 2H), 1.89(d, J=10.8 Hz, 2H) |
5B | 7.94(d, J=9.2 Hz, 1H), 7.59(d, J=8.4 Hz, 2H), 7.54(dd, J=2.4, 9.2 Hz, 1H), 7.43(d, J=8.4 Hz, 2H), 7.35(dd, J=7.6, 15.6 Hz, 5H), 7.32—7.26(m, 2H), 6.16(s, 1H), 5.18(s, 2H), 4.21(s, 2H), 3.77(t, J=5.6 Hz, 2H), 3.62(s, 3H), 2.62(s, 2H) |
5C | 8.71(s, 1H), 7.90(d, J=9.0 Hz, 1H), 7.53(d, J=9.0 Hz, 3H), 7.40(d, J=8.4 Hz, 2H), 7.31(d, J=9.6 Hz, 5H), 7.27(d, J=7.0 Hz, 2H), 6.56(s, 1H), 5.12(t, J=12.4 Hz, 2H), 4.65(s, 2H), 3.61(s, 3H), 3.11(s, 1H), 2.28(d, J=17.1 Hz, 2H), 2.04(s, 2H), 1.78(s, 1H) |
6A | 8.80(s, 2H), 8.23(d, J=8.8 Hz, 1H), 8.07—8.04(m, 2H), 7.89(d, J=8.6 Hz, 1H), 7.76(d, J=8.1 Hz, 1H), 7.67(t, J=7.6 Hz, 1H), 7.41—7.35(m, 5H), 7.34(s, 1H), 7.31(s, 1H), 5.17(s, 2H), 4.36(s, 2H), 3.68(s, 3H), 2.91(s, 2H), 2.86—2.79(m, 1H), 1.89(s, 2H), 1.71(d, J=9.5 Hz, 2H) |
6B | 8.86(s, 1H), 8.75(s, 1H), 8.17(d, J=8.8 Hz, 1H), 8.03(d, J=8.4 Hz, 1H), 7.91(s, 1H), 7.84(d, J=8.8 Hz, 1H), 7.65—7.58(m, 4H), 7.48(d, J=8.4 Hz, 3H), 7.41—7.31(m, 6H), 6.11(d, J=22.4 Hz, 1H), 5.20(d, J=13.6 Hz, 2H), 4.20(s,2H), 3.76(s, 2H), 3.63(s, 3H), 2.60(s, 2H) |
6C | 9.01(s, 1H), 8.89(s, 1H), 8.34—8.18(m, 2H), 8.06(s, 1H), 8.00(s, 1H), 7.79(s, 2H), 7.73—7.65(m, 3H), 7.64(s, 2H), 7.56(s, 1H), 7.47—7.44(m, 5H), 6.72(s, 1H), 5.31(s, 2H), 4.82(s, 2H), 3.77(s, 3H), 2.48—2.44(m, 2H), 2.21(s, 2H), 1.96(s, 1H), 1.38(s, 1H) |
7A | 8.90(s, 1H), 8.84(s, 1H), 8.25(d, J=8.9 Hz, 1H), 8.20(s, 1H), 8.09(d, J=8.4 Hz, 1H), 7.99(d, J=1.7 Hz, 1H), 7.90(d, J=8.0 Hz, 1H), 7.81(s, 1H), 7.69—7.66(m, 1H), 7.64—7.60(m, 4H), 7.39(s, 1H), 3.78(s, 3H), 3.25(d, J=12.2 Hz, 2H), 2.95—2.91(m, 1H), 2.87(t, 2H), 1.96(d, J=12.5 Hz, 2H), 1.78(t, J=15.4 Hz, 2H) |
7B | 8.54(s, 2H), 7.90(d, J=8.9 Hz, 1H), 7.79—7.75(m, 2H), 7.66(d, J=8.8 Hz, 1H), 7.47(t, J=8.0 Hz, 2H), 7.43(d, J=8.4 Hz, 2H), 7.33(d, J=7.4 Hz, 1H), 7.31—7.26(m, 2H), 7.13(s, 1H), 6.03(s, 1H), 4.33(s, 1H), 3.43(s, 3H), 3.32(s, 2H), 2.89(d, J=5.6 Hz, 2H), 2.32(s, 2H) |
7C | 8.61(s, 2H), 8.00(d, J=8.9 Hz, 1H), 7.86(d, J=8.4 Hz, 2H), 7.73(d, J=8.9 Hz, 1H), 7.60—7.54(m, 2H), 7.47(d, J=8.7 Hz, 2H), 7.38(t, J=7.5 Hz, 1H), 7.33(d, J=8.7 Hz, 2H), 7.21(s, 1H), 6.42(d, J=5.2 Hz, 1H), 4.21(s, 1H), 3.76—3.70(m, 2H), 3.51(s, 3H), 2.83—2.78(m, 1H), 2.15(d, J=17.2 Hz, 1H), 2.00(d, J=9.0 Hz, 1H), 1.91—1.83(m, 2H), 1.57(m, 1H) |
8Aa | 8.71(d, J=20.0 Hz, 2H), 8.16(d, J=8.4 Hz, 1H), 8.07(s, 1H), 8.04(d, J=8.4 Hz, 1H), 7.88(d, J=8.4 Hz, 1H), 7.78(d, J=12.2 Hz, 1H), 7.73(t, J=7.4 Hz, 1H), 7.58(t, J=7.0 Hz, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.27(s, 1H), 3.94(d, J=12.8 Hz, 1H), 3.66(s, 3H), 3.23(t, J=12.6 Hz, 1H), 2.91(t, J=12.4 Hz, 1H), 2.69(t, J=12.4 Hz, 1H), 2.11(s, 3H), 1.96(t, J=12.8 Hz, 2H), 1.65(t, J=12.2 Hz, 2H) |
8Ab | 8.76(s, 1H) , 8.70(s, 1H), 8.16(d, J=8.6 Hz, 1H), 8.07(s, 1H), 8.01(d, J=8.6 Hz, 1H,), 7.89(d, J=8.3 Hz, 1H), 7.78(d, J=7.6 Hz, 1H), 7.71(t, J=6.8 Hz, 1H), 7.58(t, J=6.9 Hz, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.13(s, 2H), 3.87(d, J=10.5 Hz, 2H), 3.65(s, 3H), 2.82—2.76(m, 4H), 1.96(d, J=11.7 Hz, 2H), 1.83(t, J=10.9 Hz, 2H) |
8Ac | 8.76—8.72(m, 1H), 8.71(s, 1H), 8.54(s, 1H), 8.16(d,J=8.4 Hz, 1H), 8.07(s, 1H), 8.04(d, J=8.4 Hz, 1H), 7.88(d, J=8.4 Hz, 1H), 7.78(d, J=12.2 Hz, 1H), 7.73(s, 1H), 7.58(s, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.27(s, 1H), 3.94(d, J=12.8 Hz, 1H), 3.66(s, 3H), 3.23(t, J=12.6 Hz, 1H), 2.91(t, J=11.4 Hz, 1H), 2.69(t, J=12.4 Hz, 1H), 1.96(t, J=16.8 Hz, 2H), 1.65(t, J=12.2 Hz, 2H) |
8Ad | 8.54(s, 1H), 8.47(d, J=1.6 Hz, 1H), 7.93(d, J=8.8 Hz, 1H), 7.87(s, 1H), 7.79(d, J=8.4 Hz, 1H), 7.64(d, J=9.2 Hz, 1H), 7.56(d, J=8.0 Hz, 1H), 7.51(t, J=7.7 Hz, 1H), 7.36—7.32(m, 1H), 7.26(s, 4H), 7.04(s, 1H), 4.46(d, J=13.2 Hz, 1H), 3.97(d, J=16.4 Hz, 4H), 3.40(s, 4H), 2.89(t, J=12.2 Hz, 2H), 2.70(t, J=12.2 Hz,1H), 2.55(t, J=12.4 Hz, 1H), 1.72(d, J=12.8 Hz, 2H) |
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
8Ae | 8.63(d, J=12.4 Hz, 1H), 8.53(s, 1H), 8.01(d, J=8.8 Hz, 1H), 7.95(d, J=7.6 Hz, 1H), 7.87(d, J=9.2 Hz, 1H), 7.66—7.56(m, 3H), 7.41—7.31(m, 5H), 7.09(d, J=15.6 Hz, 1H), 4.63(s, 1H), 3.78(s, 1H), 3.69(s, 2H), 3.50(s, 3H), 3.09(t, J=11.8 Hz, 1H), 2.71—2.62(m, 2H), 1.91—1.82(m, 2H), 1.56(t, J=10.8 Hz, 2H), 1.26(d, J=6.4 Hz, 3H) |
8Ba | 8.72(m, 2H), 8.11(d, J=8.8 Hz, 1H), 7.98—7.94(m, 2H), 7.86—7.84(m, 1H), 7.67—7.62(m, 2H), 7.57(d, J=8.4 Hz, 2H), 7.50—7.45(m, 3H), 7.31(d, J=7.2 Hz, 1H), 6.14(d, 1H), 4.18(s, 1H), 3.88—3.74(m, 3H), 3.65—3.62(m, 1H), 3.60(s, 3H), 2.57(s, 1H), 2.50(s, 1H), 2.10—2.07(m, 2H) |
8Bb | 9.52(s, 2H), 8.90(d, J=8.8 Hz, 1H), 8.73(s, 2H), 8.64(d, J=8.7 Hz, 1H), 8.40(t, J=8.0 Hz, 2H), 8.36(d, J=8.0 Hz, 2H), 8.28(t, J=7.4 Hz, 1H), 8.24(d, J=8.0 Hz, 2H), 8.09(s, 1H), 6.91(s, 1H), 4.69(s, 2H), 4.39(s, 3H), 4.24(t, J=5.2 Hz, 2H), 3.58(s, 3H), 3.42(s, 2H) |
8Bc | 8.00(d, J=7.6 Hz, 1H), 7.94(s, 1H), 7.36(t, J=8.8 Hz, 2H), 7.18(s, 2H), 7.07(d, J=7.7 Hz, 1H), 6.94(d, J=8.1 Hz, 1H), 6.88—6.82(m, 4H), 6.70(d, J=3.0 Hz, 2H), 6.56(s, 2H), 6.45(s, 1H), 3.58(s, 1H), 3.52(s, 1H), 3.18(s, 1H), 3.11(s, 1H), 2.84(s, 3H), 1.86(d, J=22.3 Hz, 2H) |
8Bd | 7.98(s, 2H), 7.36(d, J=8.9 Hz, 1H), 7.26—7.19(m, 2H), 7.11(d, J=8.8 Hz, 1H), 6.94—6.89(m, 2H), 6.84(d, J=8.0 Hz, 2H), 6.76—6.72(m, 3H), 6.58—6.56(m, 1H), 5.42—5.34(m, 1H), 3.42(d, J=21.2 Hz, 2H), 3.22(s, 2H), 3.05(t, J=5.2 Hz, 1H), 2.87(s, 3H), 2.75(t, J=5.2 Hz, 1H), 2.49(s, 1H), 1.83(s, 2H) |
8Be | 8.62(s, 2H), 8.00(d, J=8.8 Hz, 1H), 7.89—7.82(m, 2H), 7.74(d, J=8.6 Hz, 1H), 7.56—7.49(m, 5H), 7.40—7.36(m, 3H), 7.19(d, J=6.2 Hz, 1H), 6.01(d, J=18.6 Hz, 1H), 4.43—4.41(m, 1H), 4.10(s, 2H), 3.57(s, 2H), 3.50(s, 3H), 2.44(d, J=21.8 Hz, 2H), 1.22—1.17(m, 3H) |
8Ca | 8.50—8.48(d, 2H), 7.83(d, J=8.4 Hz, 2H), 7.69(t, J=8.9 Hz, 2H), 7.61(d, J=8.2 Hz, 2H), 7.44—7.32(m, 4H), 7.22(s, 2H), 6.26(dd, J=4.6, 16.5 Hz, 1H), 4.68—4.58(m, 1H), 4.34(s, 3H), 3.36(s, 3H), 2.91—2.76(m, 1H), 2.03(d, J=16.6 Hz, 1H), 1.83—1.79(m, 5H) |
8Cb | 8.55(s, 2H), 7.94(d, J=8.8 Hz, 1H), 7.78(d, J=8.1 Hz, 2H), 7.68(d, J=8.6 Hz, 1H), 7.52—7.46(m, 2H), 7.39(d, J=8.0 Hz, 2H), 7.33(t, J=7.4 Hz, 1H), 7.28(d, J=8.0 Hz, 2H), 7.16(s, 1H), 6.32(d, J=5.0 Hz, 1H), 4.26(d, J=5.1 Hz, 2H), 3.70(s, 1H), 3.43(s, 3H), 2.91(d, J=15.8 Hz, 1H), 2.69(s, 3H), 2.19(d, J=17.2 Hz, 1H), 2.08(d, J=9.5 Hz, 1H), 1.92—1.84(m, 2H) |
8Cc | 8.66—8.63(d, 2H), 8.15—8.02(m, 1H), 7.99(d, J=8.8 Hz, 1H), 7.83—7.75(m, 3H), 7.53—7.50(m, 4H), 7.33(d, J=7.7 Hz, 3H), 7.25(s, 1H), 6.42(d, J=4.3 Hz, 1H), 4.24(s, 2H), 3.49(s, 3H), 3.13(m, 2H), 2.28(t, J=16.8 Hz, 1H), 2.17—2.10(m, 1H), 1.99—1.88(m, 2H) |
8Cd | 8.59(s, 2H), 8.00(d, J=8.8 Hz, 1H), 7.84(d, J=5.6 Hz, 2H), 7.70(d, J=8.7 Hz, 1H), 7.52(d, J=4.1 Hz, 2H), 7.43—7.36(m, 3H), 7.31(d, J=7.9 Hz, 2H), 7.20(d, J=4.4 Hz, 1H), 6.37—6.33(m, 1H), 4.18(d, J=5.1 Hz, 1H), 4.10—4.02(m, 1H), 3.47(s, 3H), 3.44(s, 2H), 3.06—2.90(m, 2H), 2.32—2.11(m, 2H), 1.94—1.78(m, 3H) |
8Ce | 8.62(d, 2H), 8.01—7.93(d, J=8.4 Hz, 4H), 7.41(d, J=7.6 Hz, 5H), 7.36—7.23(m, 3H), 6.39(s, 1H), 4.72(m, 1H), 4.57—4.49(m, 1H), 4.35—4.26(m, 1H), 4.20(s, 2H), 3.50(s, 3H), 3.16—2.93(m, 1H), 2.16—1.84(m, 4H), 1.23(d, J=5.8 Hz, 3H) |
Table 3 1H NMR data of compounds 2—8
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
---|---|
2A | 10.68(s, 1H), 9.44(s, 1H), 7.84(d, J=8.8 Hz, 1H), 7.73—7.71(m, 1H), 7.60(s, 1H), 7.38—7.33(m, 5H), 7.25(d, J=8.4 Hz, 2H), 7.11(d, J=8.4 Hz, 2H), 5.29(s, 1H), 5.16(s, 2H), 4.36(s, 2H), 2.91(s, 2H), 2.78—2.71(m, 1H), 1.88(d, J=12.0 Hz, 2H), 1.66(d, J=10.8 Hz, 2H) |
2B | 10.45(s, 1H), 9.31(s, 1H), 7.76(d, J=8.0 Hz, 1H), 7.69(s, 1H), 7.63(d, J=8.4 Hz, 1H), 7.32—7.25(m, 7H), 7.04(d, J=7.4 Hz, 2H), 6.02(s, 1H), 5.12(s, 2H), 4.12(s, 2H), 3.68(s, 2H), 2.49(s, 2H) |
2C | 10.52(s, 1H), 9.44(s, 1H), 7.86(d, J=8.8 Hz, 1H), 7.78—7.74(m, 2H), 7.37(s, 5H), 7.34(s, 2H), 7.07(d, J=8.0 Hz, 2H), 6.47(s, 1H), 5.19—5.12(m, 2H), 4.63(s, 2H), 3.17—3.05(m, 1H), 2.26(d, J=16.8 Hz, 2H), 2.04(s, 2H), 1.78—1.68(m, 1H) |
3A | 8.56(s, 1H), 7.95(s, 1H), 7.85(d, J=8.2 Hz, 1H), 7.48(d, J=8.4 Hz, 1H), 7.37—7.26(m, 5H), 7.03(d, J=8.2 Hz, 2H), 6.60(d, J=8.2 Hz, 2H), 6.08(s, 1H), 5.16(s, 2H), 4.30(s, 2H), 4.13(s, 2H), 2.84(s, 2H), 2.56(t, J=11.9 Hz, 1H), 1.78(d, J=12.4 Hz, 2H), 1.61—1.51(m, 2H) |
3B | 8.55(s, 1H), 7.92(d, J=2.0 Hz, 1H), 7.82(d, J=8.8 Hz, 1H), 7.47(dd, J=2.0, 8.8 Hz, 1H), 7.36—7.29(m, 5H), 7.20(d, J=8.8 Hz, 2H), 6.58(d, J=8.8 Hz, 2H), 6.01(s, 1H), 5.87(s, 1H), 5.16(s, 2H), 4.11(s, 4H), 3.67(t, J=5.6 Hz, 2H), 2.46(s, 2H) |
3C | 8.55(s, 1H), 7.94(s, 1H), 7.82(d, J=8.9 Hz, 1H), 7.48—7.46(m, 1H), 7.32—7.26(m, 5H), 7.17(d, J=7.6 Hz, 2H), 6.56(d, J=8.3 Hz, 2H), 6.29—6.21(m, 2H), 5.13(d, J=12.9 Hz, 2H), 4.58(s, 2H), 4.16(s, 2H), 3.11—2.96(m, 1H), 2.16(d, J=9.4 Hz, 2H), 1.94(d, J=8.0 Hz, 2H), 1.68(s, 1H) |
4A | 11.87(s, 1H), 9.03(s, 1H), 8.15(d, J=9.2 Hz, 1H), 7.85—7.80(m, 5H), 7.64—7.59(m, 4H), 7.28(s, 1H), 5.85(s, 2H), 5.37(s, 2H), 4.49(d, J=13.2 Hz, 2H), 3.18—3.12(m, 3H), 2.14(d, J=12.3 Hz, 2H), 1.92(s, 1H) |
4B | 9.09(s, 1H), 8.55(s, 1H), 7.92(d, J=2.4 Hz, 1H), 7.82(d, J=9.2 Hz, 1H), 7.47(dd, J=2.4, 9.2 Hz, 1H), 7.36—7.29(m, 5H), 7.25(d, J=8.4 Hz, 2H), 6.64(d, J=8.4 Hz, 2H), 6.04(s, 1H), 5.38(s, 2H), 3.93(s, 2H), 3.64(t, J=5.6 Hz, 2H), 2.90(s, 2H) |
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
4C | 8.14(t, J=7.5 Hz, 2H), 7.93(s, 2H), 7.83(d, J=8.8 Hz, 3H), 7.58(s, 2H), 7.52(t, J=7.3 Hz, 2H), 7.49(s, 2H), 6.97(d, J=5.1 Hz, 1H), 4.81—4.74(m, 2H), 3.70(s, 1H), 3.31(s, 1H), 3.07(s, 1H), 2.90(s, 1H), 2.63(d, J=13.2 Hz, 1H), 2.41(s, 1H), 2.21(s, 2H), 2.01(s, 1H) |
5A | 8.88(s, 1H), 8.08(d, J=9.0 Hz, 1H), 7.70(d, J=17.8 Hz, 1H), 7.61(d, J=8.2 Hz, 4H), 7.56—7.45(m, 6H), 5.31(s, 2H), 4.53(s, 2H), 3.78(s, 3H), 3.08(s, 2H), 3.01(t, J=12.2 Hz, 1H), 2.11(d, J=11.4 Hz, 2H), 1.89(d, J=10.8 Hz, 2H) |
5B | 7.94(d, J=9.2 Hz, 1H), 7.59(d, J=8.4 Hz, 2H), 7.54(dd, J=2.4, 9.2 Hz, 1H), 7.43(d, J=8.4 Hz, 2H), 7.35(dd, J=7.6, 15.6 Hz, 5H), 7.32—7.26(m, 2H), 6.16(s, 1H), 5.18(s, 2H), 4.21(s, 2H), 3.77(t, J=5.6 Hz, 2H), 3.62(s, 3H), 2.62(s, 2H) |
5C | 8.71(s, 1H), 7.90(d, J=9.0 Hz, 1H), 7.53(d, J=9.0 Hz, 3H), 7.40(d, J=8.4 Hz, 2H), 7.31(d, J=9.6 Hz, 5H), 7.27(d, J=7.0 Hz, 2H), 6.56(s, 1H), 5.12(t, J=12.4 Hz, 2H), 4.65(s, 2H), 3.61(s, 3H), 3.11(s, 1H), 2.28(d, J=17.1 Hz, 2H), 2.04(s, 2H), 1.78(s, 1H) |
6A | 8.80(s, 2H), 8.23(d, J=8.8 Hz, 1H), 8.07—8.04(m, 2H), 7.89(d, J=8.6 Hz, 1H), 7.76(d, J=8.1 Hz, 1H), 7.67(t, J=7.6 Hz, 1H), 7.41—7.35(m, 5H), 7.34(s, 1H), 7.31(s, 1H), 5.17(s, 2H), 4.36(s, 2H), 3.68(s, 3H), 2.91(s, 2H), 2.86—2.79(m, 1H), 1.89(s, 2H), 1.71(d, J=9.5 Hz, 2H) |
6B | 8.86(s, 1H), 8.75(s, 1H), 8.17(d, J=8.8 Hz, 1H), 8.03(d, J=8.4 Hz, 1H), 7.91(s, 1H), 7.84(d, J=8.8 Hz, 1H), 7.65—7.58(m, 4H), 7.48(d, J=8.4 Hz, 3H), 7.41—7.31(m, 6H), 6.11(d, J=22.4 Hz, 1H), 5.20(d, J=13.6 Hz, 2H), 4.20(s,2H), 3.76(s, 2H), 3.63(s, 3H), 2.60(s, 2H) |
6C | 9.01(s, 1H), 8.89(s, 1H), 8.34—8.18(m, 2H), 8.06(s, 1H), 8.00(s, 1H), 7.79(s, 2H), 7.73—7.65(m, 3H), 7.64(s, 2H), 7.56(s, 1H), 7.47—7.44(m, 5H), 6.72(s, 1H), 5.31(s, 2H), 4.82(s, 2H), 3.77(s, 3H), 2.48—2.44(m, 2H), 2.21(s, 2H), 1.96(s, 1H), 1.38(s, 1H) |
7A | 8.90(s, 1H), 8.84(s, 1H), 8.25(d, J=8.9 Hz, 1H), 8.20(s, 1H), 8.09(d, J=8.4 Hz, 1H), 7.99(d, J=1.7 Hz, 1H), 7.90(d, J=8.0 Hz, 1H), 7.81(s, 1H), 7.69—7.66(m, 1H), 7.64—7.60(m, 4H), 7.39(s, 1H), 3.78(s, 3H), 3.25(d, J=12.2 Hz, 2H), 2.95—2.91(m, 1H), 2.87(t, 2H), 1.96(d, J=12.5 Hz, 2H), 1.78(t, J=15.4 Hz, 2H) |
7B | 8.54(s, 2H), 7.90(d, J=8.9 Hz, 1H), 7.79—7.75(m, 2H), 7.66(d, J=8.8 Hz, 1H), 7.47(t, J=8.0 Hz, 2H), 7.43(d, J=8.4 Hz, 2H), 7.33(d, J=7.4 Hz, 1H), 7.31—7.26(m, 2H), 7.13(s, 1H), 6.03(s, 1H), 4.33(s, 1H), 3.43(s, 3H), 3.32(s, 2H), 2.89(d, J=5.6 Hz, 2H), 2.32(s, 2H) |
7C | 8.61(s, 2H), 8.00(d, J=8.9 Hz, 1H), 7.86(d, J=8.4 Hz, 2H), 7.73(d, J=8.9 Hz, 1H), 7.60—7.54(m, 2H), 7.47(d, J=8.7 Hz, 2H), 7.38(t, J=7.5 Hz, 1H), 7.33(d, J=8.7 Hz, 2H), 7.21(s, 1H), 6.42(d, J=5.2 Hz, 1H), 4.21(s, 1H), 3.76—3.70(m, 2H), 3.51(s, 3H), 2.83—2.78(m, 1H), 2.15(d, J=17.2 Hz, 1H), 2.00(d, J=9.0 Hz, 1H), 1.91—1.83(m, 2H), 1.57(m, 1H) |
8Aa | 8.71(d, J=20.0 Hz, 2H), 8.16(d, J=8.4 Hz, 1H), 8.07(s, 1H), 8.04(d, J=8.4 Hz, 1H), 7.88(d, J=8.4 Hz, 1H), 7.78(d, J=12.2 Hz, 1H), 7.73(t, J=7.4 Hz, 1H), 7.58(t, J=7.0 Hz, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.27(s, 1H), 3.94(d, J=12.8 Hz, 1H), 3.66(s, 3H), 3.23(t, J=12.6 Hz, 1H), 2.91(t, J=12.4 Hz, 1H), 2.69(t, J=12.4 Hz, 1H), 2.11(s, 3H), 1.96(t, J=12.8 Hz, 2H), 1.65(t, J=12.2 Hz, 2H) |
8Ab | 8.76(s, 1H) , 8.70(s, 1H), 8.16(d, J=8.6 Hz, 1H), 8.07(s, 1H), 8.01(d, J=8.6 Hz, 1H,), 7.89(d, J=8.3 Hz, 1H), 7.78(d, J=7.6 Hz, 1H), 7.71(t, J=6.8 Hz, 1H), 7.58(t, J=6.9 Hz, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.13(s, 2H), 3.87(d, J=10.5 Hz, 2H), 3.65(s, 3H), 2.82—2.76(m, 4H), 1.96(d, J=11.7 Hz, 2H), 1.83(t, J=10.9 Hz, 2H) |
8Ac | 8.76—8.72(m, 1H), 8.71(s, 1H), 8.54(s, 1H), 8.16(d,J=8.4 Hz, 1H), 8.07(s, 1H), 8.04(d, J=8.4 Hz, 1H), 7.88(d, J=8.4 Hz, 1H), 7.78(d, J=12.2 Hz, 1H), 7.73(s, 1H), 7.58(s, 1H), 7.48(s, 4H), 7.26(s, 1H), 4.27(s, 1H), 3.94(d, J=12.8 Hz, 1H), 3.66(s, 3H), 3.23(t, J=12.6 Hz, 1H), 2.91(t, J=11.4 Hz, 1H), 2.69(t, J=12.4 Hz, 1H), 1.96(t, J=16.8 Hz, 2H), 1.65(t, J=12.2 Hz, 2H) |
8Ad | 8.54(s, 1H), 8.47(d, J=1.6 Hz, 1H), 7.93(d, J=8.8 Hz, 1H), 7.87(s, 1H), 7.79(d, J=8.4 Hz, 1H), 7.64(d, J=9.2 Hz, 1H), 7.56(d, J=8.0 Hz, 1H), 7.51(t, J=7.7 Hz, 1H), 7.36—7.32(m, 1H), 7.26(s, 4H), 7.04(s, 1H), 4.46(d, J=13.2 Hz, 1H), 3.97(d, J=16.4 Hz, 4H), 3.40(s, 4H), 2.89(t, J=12.2 Hz, 2H), 2.70(t, J=12.2 Hz,1H), 2.55(t, J=12.4 Hz, 1H), 1.72(d, J=12.8 Hz, 2H) |
Compd. | 1H NMR(CDCl3, 400 MHz), δ |
8Ae | 8.63(d, J=12.4 Hz, 1H), 8.53(s, 1H), 8.01(d, J=8.8 Hz, 1H), 7.95(d, J=7.6 Hz, 1H), 7.87(d, J=9.2 Hz, 1H), 7.66—7.56(m, 3H), 7.41—7.31(m, 5H), 7.09(d, J=15.6 Hz, 1H), 4.63(s, 1H), 3.78(s, 1H), 3.69(s, 2H), 3.50(s, 3H), 3.09(t, J=11.8 Hz, 1H), 2.71—2.62(m, 2H), 1.91—1.82(m, 2H), 1.56(t, J=10.8 Hz, 2H), 1.26(d, J=6.4 Hz, 3H) |
8Ba | 8.72(m, 2H), 8.11(d, J=8.8 Hz, 1H), 7.98—7.94(m, 2H), 7.86—7.84(m, 1H), 7.67—7.62(m, 2H), 7.57(d, J=8.4 Hz, 2H), 7.50—7.45(m, 3H), 7.31(d, J=7.2 Hz, 1H), 6.14(d, 1H), 4.18(s, 1H), 3.88—3.74(m, 3H), 3.65—3.62(m, 1H), 3.60(s, 3H), 2.57(s, 1H), 2.50(s, 1H), 2.10—2.07(m, 2H) |
8Bb | 9.52(s, 2H), 8.90(d, J=8.8 Hz, 1H), 8.73(s, 2H), 8.64(d, J=8.7 Hz, 1H), 8.40(t, J=8.0 Hz, 2H), 8.36(d, J=8.0 Hz, 2H), 8.28(t, J=7.4 Hz, 1H), 8.24(d, J=8.0 Hz, 2H), 8.09(s, 1H), 6.91(s, 1H), 4.69(s, 2H), 4.39(s, 3H), 4.24(t, J=5.2 Hz, 2H), 3.58(s, 3H), 3.42(s, 2H) |
8Bc | 8.00(d, J=7.6 Hz, 1H), 7.94(s, 1H), 7.36(t, J=8.8 Hz, 2H), 7.18(s, 2H), 7.07(d, J=7.7 Hz, 1H), 6.94(d, J=8.1 Hz, 1H), 6.88—6.82(m, 4H), 6.70(d, J=3.0 Hz, 2H), 6.56(s, 2H), 6.45(s, 1H), 3.58(s, 1H), 3.52(s, 1H), 3.18(s, 1H), 3.11(s, 1H), 2.84(s, 3H), 1.86(d, J=22.3 Hz, 2H) |
8Bd | 7.98(s, 2H), 7.36(d, J=8.9 Hz, 1H), 7.26—7.19(m, 2H), 7.11(d, J=8.8 Hz, 1H), 6.94—6.89(m, 2H), 6.84(d, J=8.0 Hz, 2H), 6.76—6.72(m, 3H), 6.58—6.56(m, 1H), 5.42—5.34(m, 1H), 3.42(d, J=21.2 Hz, 2H), 3.22(s, 2H), 3.05(t, J=5.2 Hz, 1H), 2.87(s, 3H), 2.75(t, J=5.2 Hz, 1H), 2.49(s, 1H), 1.83(s, 2H) |
8Be | 8.62(s, 2H), 8.00(d, J=8.8 Hz, 1H), 7.89—7.82(m, 2H), 7.74(d, J=8.6 Hz, 1H), 7.56—7.49(m, 5H), 7.40—7.36(m, 3H), 7.19(d, J=6.2 Hz, 1H), 6.01(d, J=18.6 Hz, 1H), 4.43—4.41(m, 1H), 4.10(s, 2H), 3.57(s, 2H), 3.50(s, 3H), 2.44(d, J=21.8 Hz, 2H), 1.22—1.17(m, 3H) |
8Ca | 8.50—8.48(d, 2H), 7.83(d, J=8.4 Hz, 2H), 7.69(t, J=8.9 Hz, 2H), 7.61(d, J=8.2 Hz, 2H), 7.44—7.32(m, 4H), 7.22(s, 2H), 6.26(dd, J=4.6, 16.5 Hz, 1H), 4.68—4.58(m, 1H), 4.34(s, 3H), 3.36(s, 3H), 2.91—2.76(m, 1H), 2.03(d, J=16.6 Hz, 1H), 1.83—1.79(m, 5H) |
8Cb | 8.55(s, 2H), 7.94(d, J=8.8 Hz, 1H), 7.78(d, J=8.1 Hz, 2H), 7.68(d, J=8.6 Hz, 1H), 7.52—7.46(m, 2H), 7.39(d, J=8.0 Hz, 2H), 7.33(t, J=7.4 Hz, 1H), 7.28(d, J=8.0 Hz, 2H), 7.16(s, 1H), 6.32(d, J=5.0 Hz, 1H), 4.26(d, J=5.1 Hz, 2H), 3.70(s, 1H), 3.43(s, 3H), 2.91(d, J=15.8 Hz, 1H), 2.69(s, 3H), 2.19(d, J=17.2 Hz, 1H), 2.08(d, J=9.5 Hz, 1H), 1.92—1.84(m, 2H) |
8Cc | 8.66—8.63(d, 2H), 8.15—8.02(m, 1H), 7.99(d, J=8.8 Hz, 1H), 7.83—7.75(m, 3H), 7.53—7.50(m, 4H), 7.33(d, J=7.7 Hz, 3H), 7.25(s, 1H), 6.42(d, J=4.3 Hz, 1H), 4.24(s, 2H), 3.49(s, 3H), 3.13(m, 2H), 2.28(t, J=16.8 Hz, 1H), 2.17—2.10(m, 1H), 1.99—1.88(m, 2H) |
8Cd | 8.59(s, 2H), 8.00(d, J=8.8 Hz, 1H), 7.84(d, J=5.6 Hz, 2H), 7.70(d, J=8.7 Hz, 1H), 7.52(d, J=4.1 Hz, 2H), 7.43—7.36(m, 3H), 7.31(d, J=7.9 Hz, 2H), 7.20(d, J=4.4 Hz, 1H), 6.37—6.33(m, 1H), 4.18(d, J=5.1 Hz, 1H), 4.10—4.02(m, 1H), 3.47(s, 3H), 3.44(s, 2H), 3.06—2.90(m, 2H), 2.32—2.11(m, 2H), 1.94—1.78(m, 3H) |
8Ce | 8.62(d, 2H), 8.01—7.93(d, J=8.4 Hz, 4H), 7.41(d, J=7.6 Hz, 5H), 7.36—7.23(m, 3H), 6.39(s, 1H), 4.72(m, 1H), 4.57—4.49(m, 1H), 4.35—4.26(m, 1H), 4.20(s, 2H), 3.50(s, 3H), 3.16—2.93(m, 1H), 2.16—1.84(m, 4H), 1.23(d, J=5.8 Hz, 3H) |
Compd. | 13C NMR(CDCl3, 150 MHz), δ |
---|---|
8Aa | 169.3, 153.4, 148.5, 147.4, 146.5, 143.9, 134.7, 133.4, 132.8, 132.3, 132.2, 130.3, 129.8, 129.5, 128.5, 128.2, 128.1, 127.6, 127.4, 127.0, 126.1, 122.9, 118.6, 115.0, 47.9, 46.6, 33.4, 32.2, 27.4, 20.7 |
8Ab | 153.6, 148.7, 147.4, 146.7, 144.1, 135.0, 133.6, 133.1, 132.6, 132.4, 130.6, 130.0, 129.7, 128.7, 128.3, 127.7, 127.5, 127.3, 126.3, 123.0, 118.8, 115.2, 46.1, 41.5, 34.5, 32.6, 27.6 |
8Ac | 163.9, 163.6, 163.3, 150.4, 150.0, 148.9, 136.5, 135.1, 134.7, 133.4, 132.6, 131.9, 131.5, 130.8, 130.5, 130.3, 130.1, 130.0, 129.2, 128.9, 128.8, 128.5, 120.5, 48.3, 43.7, 34.5, 29.1 |
8Ad | 169.7, 153.5, 148.6, 147.3, 146.6, 144.0, 134.9, 133.6, 133.0, 132.5, 132.3, 130.4, 129.9, 129.6, 128.7, 128.6, 128.3, 128.2, 127.7, 127.5, 127.2, 126.2, 123.0, 118.7, 115.1, 59.5, 43.8, 42.6, 41.9, 33.2, 32.2, 27.5 |
8Ae | 173.0, 172.9, 153.1, 146.9, 146.6, 143.8, 134.3, 132.8, 132.2, 131.9, 130.5, 129.5, 129.1, 128.4, 128.0, 127.4, 127.2, 127.0, 126.8, 125.6, 122.7, 118.2, 114.7, 64.0, 45.1, 42.7, 41.8, 33.3, 32.2, 27.4, 21.1 |
Compd. | 13C NMR(CDCl3, 150 MHz), δ |
8Ba | 169.5, 153.5, 148.6, 146.7, 143.9, 142.1, 133.9, 133.7, 133.6, 132.2, 130.3, 130.0, 128.5, 128.2, 127.7, 127.5, 127.4, 127.3, 127.2, 126.4, 126.3, 123.1, 122.7, 121.3, 118.7, 115.2, 45.6, 42.0, 27.6, 26.9, 20.9 |
8Bb | 153.5, 148.5, 146.7, 143.6, 142.0, 135.0, 134.4, 133.9, 133.6, 132.2, 132.0, 130.1, 128.6, 128.2, 127.7, 127.6, 127.4, 126.6, 126.4, 123.2, 121.3, 118.7, 115.1, 44.8, 42.4, 35.1, 27.7, 27.3 |
8Bc | 153.6, 148.8, 146.8, 144.2, 141.4, 135.0, 133.9, 133.7, 132.5, 130.8, 130.1, 128.7, 128.4, 128.1, 127.8, 127.4, 126.6, 126.3, 125.6, 123.2, 122.2, 121.7, 118.9, 117.6, 115.3, 110.5, 46.5, 43.5, 39.8, 28.0 |
8Bd | 169.5, 153.5, 148.4, 146.5, 143.9, 141.9, 134.8, 133.9, 133.6, 132.4, 132.2, 130.3, 130.0, 129.6, 128.5, 128.0, 127.6, 127.2, 126.4, 126.2, 126.1, 123.0, 122.0, 120.5, 118.6, 115.1, 59.8, 42.7, 40.4, 38.7, 27.5 |
8Be | 173.3, 153.4, 148.3, 146.4, 143.7, 141.8, 134.7, 133.7, 133.6, 132.2, 132.1, 130.1, 130.0, 128.4, 127.9, 127.6, 127.5, 127.1, 126.2, 126.1, 126.0, 123.0, 122.0, 120.9, 118.5, 115.0, 64.5, 44.2, 41.5, 29.1, 27.4, 20.3 |
8Ca | 167.1, 166.5, 153.2, 148.0, 146.2, 143.3, 141.0, 134.4, 133.4, 132.0, 129.6, 129.2, 128.3, 128.1, 127.6, 127.3, 126.9, 126.1, 125.9, 122.8, 118.3, 114.7, 54.6, 53.3, 50.6, 49.7, 37.0, 29.6, 20.4 |
8Cb | 153.5, 148.5, 146.7, 143.8, 141.2, 134.9, 133.9, 133.4, 132.7, 132.2, 130.3, 130.0, 129.8, 128.6, 128.5, 128.3, 127.7, 127.6, 127.3, 126.3, 126.2, 123.1, 118.6, 115.1, 55.4, 54.9, 40.3, 36.8, 35.2, 30.1, 27.6 |
8Cc | 153.4, 148.3, 146.4, 143.5, 141.3, 134.8, 133.5, 132.9, 132.8, 132.0, 129.9, 129.2, 128.6, 128.2, 127.8, 127.5, 127.2, 126.2, 123.0, 118.6, 115.0, 54.8, 51.8, 38.1, 34.4, 29.7, 27.7 |
8Cd | 167.8, 166.9, 153.5, 148.8, 146.9, 144.2, 141.2, 134.9, 134.1, 133.4, 132.4, 132.3, 130.8, 129.9, 129.5, 128.6, 128.2, 127.6, 127.2, 126.5, 126.1, 123.1, 118.6, 115.2, 59.8, 52.3, 51.5, 37.4, 35.0, 30.2, 28.1 |
8Ce | 170.9, 170.1, 153.3, 148.3, 146.4, 143.6, 141.1, 134.6, 133.6, 132.0, 130.0, 129.5, 129.1, 128.8, 128.2, 127.4, 127.1, 126.2, 126.0, 122.9, 118.4, 114.9, 65.5, 53.3, 51.2, 37.6, 34.7, 30.0, 27.8, 21.0 |
Table 4 13C NMR data of compounds 8
Compd. | 13C NMR(CDCl3, 150 MHz), δ |
---|---|
8Aa | 169.3, 153.4, 148.5, 147.4, 146.5, 143.9, 134.7, 133.4, 132.8, 132.3, 132.2, 130.3, 129.8, 129.5, 128.5, 128.2, 128.1, 127.6, 127.4, 127.0, 126.1, 122.9, 118.6, 115.0, 47.9, 46.6, 33.4, 32.2, 27.4, 20.7 |
8Ab | 153.6, 148.7, 147.4, 146.7, 144.1, 135.0, 133.6, 133.1, 132.6, 132.4, 130.6, 130.0, 129.7, 128.7, 128.3, 127.7, 127.5, 127.3, 126.3, 123.0, 118.8, 115.2, 46.1, 41.5, 34.5, 32.6, 27.6 |
8Ac | 163.9, 163.6, 163.3, 150.4, 150.0, 148.9, 136.5, 135.1, 134.7, 133.4, 132.6, 131.9, 131.5, 130.8, 130.5, 130.3, 130.1, 130.0, 129.2, 128.9, 128.8, 128.5, 120.5, 48.3, 43.7, 34.5, 29.1 |
8Ad | 169.7, 153.5, 148.6, 147.3, 146.6, 144.0, 134.9, 133.6, 133.0, 132.5, 132.3, 130.4, 129.9, 129.6, 128.7, 128.6, 128.3, 128.2, 127.7, 127.5, 127.2, 126.2, 123.0, 118.7, 115.1, 59.5, 43.8, 42.6, 41.9, 33.2, 32.2, 27.5 |
8Ae | 173.0, 172.9, 153.1, 146.9, 146.6, 143.8, 134.3, 132.8, 132.2, 131.9, 130.5, 129.5, 129.1, 128.4, 128.0, 127.4, 127.2, 127.0, 126.8, 125.6, 122.7, 118.2, 114.7, 64.0, 45.1, 42.7, 41.8, 33.3, 32.2, 27.4, 21.1 |
Compd. | 13C NMR(CDCl3, 150 MHz), δ |
8Ba | 169.5, 153.5, 148.6, 146.7, 143.9, 142.1, 133.9, 133.7, 133.6, 132.2, 130.3, 130.0, 128.5, 128.2, 127.7, 127.5, 127.4, 127.3, 127.2, 126.4, 126.3, 123.1, 122.7, 121.3, 118.7, 115.2, 45.6, 42.0, 27.6, 26.9, 20.9 |
8Bb | 153.5, 148.5, 146.7, 143.6, 142.0, 135.0, 134.4, 133.9, 133.6, 132.2, 132.0, 130.1, 128.6, 128.2, 127.7, 127.6, 127.4, 126.6, 126.4, 123.2, 121.3, 118.7, 115.1, 44.8, 42.4, 35.1, 27.7, 27.3 |
8Bc | 153.6, 148.8, 146.8, 144.2, 141.4, 135.0, 133.9, 133.7, 132.5, 130.8, 130.1, 128.7, 128.4, 128.1, 127.8, 127.4, 126.6, 126.3, 125.6, 123.2, 122.2, 121.7, 118.9, 117.6, 115.3, 110.5, 46.5, 43.5, 39.8, 28.0 |
8Bd | 169.5, 153.5, 148.4, 146.5, 143.9, 141.9, 134.8, 133.9, 133.6, 132.4, 132.2, 130.3, 130.0, 129.6, 128.5, 128.0, 127.6, 127.2, 126.4, 126.2, 126.1, 123.0, 122.0, 120.5, 118.6, 115.1, 59.8, 42.7, 40.4, 38.7, 27.5 |
8Be | 173.3, 153.4, 148.3, 146.4, 143.7, 141.8, 134.7, 133.7, 133.6, 132.2, 132.1, 130.1, 130.0, 128.4, 127.9, 127.6, 127.5, 127.1, 126.2, 126.1, 126.0, 123.0, 122.0, 120.9, 118.5, 115.0, 64.5, 44.2, 41.5, 29.1, 27.4, 20.3 |
8Ca | 167.1, 166.5, 153.2, 148.0, 146.2, 143.3, 141.0, 134.4, 133.4, 132.0, 129.6, 129.2, 128.3, 128.1, 127.6, 127.3, 126.9, 126.1, 125.9, 122.8, 118.3, 114.7, 54.6, 53.3, 50.6, 49.7, 37.0, 29.6, 20.4 |
8Cb | 153.5, 148.5, 146.7, 143.8, 141.2, 134.9, 133.9, 133.4, 132.7, 132.2, 130.3, 130.0, 129.8, 128.6, 128.5, 128.3, 127.7, 127.6, 127.3, 126.3, 126.2, 123.1, 118.6, 115.1, 55.4, 54.9, 40.3, 36.8, 35.2, 30.1, 27.6 |
8Cc | 153.4, 148.3, 146.4, 143.5, 141.3, 134.8, 133.5, 132.9, 132.8, 132.0, 129.9, 129.2, 128.6, 128.2, 127.8, 127.5, 127.2, 126.2, 123.0, 118.6, 115.0, 54.8, 51.8, 38.1, 34.4, 29.7, 27.7 |
8Cd | 167.8, 166.9, 153.5, 148.8, 146.9, 144.2, 141.2, 134.9, 134.1, 133.4, 132.4, 132.3, 130.8, 129.9, 129.5, 128.6, 128.2, 127.6, 127.2, 126.5, 126.1, 123.1, 118.6, 115.2, 59.8, 52.3, 51.5, 37.4, 35.0, 30.2, 28.1 |
8Ce | 170.9, 170.1, 153.3, 148.3, 146.4, 143.6, 141.1, 134.6, 133.6, 132.0, 130.0, 129.5, 129.1, 128.8, 128.2, 127.4, 127.1, 126.2, 126.0, 122.9, 118.4, 114.9, 65.5, 53.3, 51.2, 37.6, 34.7, 30.0, 27.8, 21.0 |
Compd. | IC50/(nmol·L-1) | Compd. | IC50/(nmol·L-1) | ||
---|---|---|---|---|---|
mTOR | PI3Kα | mTOR | PI3Kα | ||
8Aa | <10 | <100 | 8Bd | <10 | <100 |
8Ab | <10 | <100 | 8Be | <10 | <100 |
8Ac | <10 | <100 | 8Ca | <10 | <100 |
8Ad | <10 | <100 | 8Cb | <10 | <100 |
8Ae | <10 | <100 | 8Cc | <10 | <100 |
8Ba | <10 | <100 | 8Cd | <10 | <100 |
8Bb | <10 | <100 | 8Ce | <10 | <100 |
8Bc | <10 | <100 |
Table 5 Inhibition activity of compounds 8 against mTOR and PI3-Kinase
Compd. | IC50/(nmol·L-1) | Compd. | IC50/(nmol·L-1) | ||
---|---|---|---|---|---|
mTOR | PI3Kα | mTOR | PI3Kα | ||
8Aa | <10 | <100 | 8Bd | <10 | <100 |
8Ab | <10 | <100 | 8Be | <10 | <100 |
8Ac | <10 | <100 | 8Ca | <10 | <100 |
8Ad | <10 | <100 | 8Cb | <10 | <100 |
8Ae | <10 | <100 | 8Cc | <10 | <100 |
8Ba | <10 | <100 | 8Cd | <10 | <100 |
8Bb | <10 | <100 | 8Ce | <10 | <100 |
8Bc | <10 | <100 |
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