CN1867553A - 作为cdk 和/或vegf 抑制剂的氨基亚砜取代的嘧啶化合物、其制备方法以及作为药物的用途 - Google Patents
作为cdk 和/或vegf 抑制剂的氨基亚砜取代的嘧啶化合物、其制备方法以及作为药物的用途 Download PDFInfo
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- CN1867553A CN1867553A CNA2004800304726A CN200480030472A CN1867553A CN 1867553 A CN1867553 A CN 1867553A CN A2004800304726 A CNA2004800304726 A CN A2004800304726A CN 200480030472 A CN200480030472 A CN 200480030472A CN 1867553 A CN1867553 A CN 1867553A
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Abstract
Description
实施例号 | 增殖作用IC50[μM] | ||||
MCF7 | H460 | HCT116 | DU145 | MaTu-ADR | |
1.0 | 0.3 | 1.2 | 0.4 | 1.5 | 1.6 |
2.0 | 1.5 | 0.3 | 0.3 | 1.7 | 0.4 |
1.3 | <0.1 | 0.14 | 0.10 | 0.2 | 0.17 |
1.4 | 0.06 | 0.06 | 0.05 | 0.10 | 0.08 |
1.2 | 0.11 | 0.03 | 0.02 | 0.04 | 0.04 |
2.1 | 0.9 | ||||
2.3 | 0.3 | 0.4 | 0.19 | 0.12 | |
1.23 | 0.13 | <0.1 | 0.1 | <0.1 | |
1.24 | <0.1 | 0.07 | 0.13 | 0.08 | |
1.25 | <0.1 | ||||
1.31 | 0.2 | 0.18 | 0.3 | 0.7 | |
1.41 | 0.08 | 0.07 | 0.09 | 0.07 | |
1.42 | 0.15 | <0.1 | 0.17 | <0.1 |
实施例号 | 增殖作用IC50[μM] | ||||
MCF7 | H460 | HCT116 | DU145 | MaTu-ADR | |
1.7 | 1.1 | ||||
1.26 | 0.06 | 0.03 | 0.07 | 0.04 | |
1.27 | 0.06 | 0.02 | 0.13 | 0.03 | |
1.10 | 0.5 | 0.7 | 0.8 | 0.8 | |
1.39 | 0.3 | 0.3 | 0.3 | 0.9 | |
1.33 | 1 | ||||
1.35 | 0.11 | 0.12 | 0.12 | 0.3 | |
1.34 | 0.8 | ||||
1.40 | 0.11 | 0.17 | 0.18 | 0.3 | |
1.63 | 0.9 | ||||
1.48 | 0.3 | 0.3 | 0.4 | 0.6 | |
1.54 | 0.11 | 0.12 | 0.19 | 0.07 | |
1.11 | 0.1 | <0.1 | <0.1 | 0.1 | |
1.9 | 0.1 | 0.11 | 0.1 | 0.1 | |
1.12 | 0.2 | 0.4 | 0.3 | 2.8 | |
1.6 | 0.14 | <0.1 | <0.1 | <0.1 | |
1.37 | 0.17 | <0.1 | 0.16 | 0.3 | |
1.57 | <0.1 | 0.12 | 0.11 | 0.09 | |
1.49 | 0.3 | 0.4 | 0.3 | 0.6 |
实施例号 | 增殖作用IC50[μM] | ||||
MCF7 | H460 | HCT116 | DU145 | MaTu-ADR | |
1.50 | 1.2 | ||||
1.55 | 0.3 | 0.3 | 0.3 | 0.15 | |
1.56 | 0.02 | 0.1 | 0.07 | 0.05 | |
1.46 | 0.2 | 0.11 | 0.17 | 0.2 | |
1.47 | 0.6 | 0.6 | 0.6 | 0.8 | |
1.16 | 0.18 | 0.2 | 0.19 | 4.0 | |
1.20 | 0.2 | 0.4 | 0.4 | 2.1 | |
1.38 | 0.12 | 0.06 | 0.13 | 0.4 | |
1.36 | 0.14 | 0.12 | 0.17 | 1.2 | |
1.51 | 0.08 | 0.05 | 0.05 | 0.06 | |
1.60 | 0.06 | 0.04 | 0.04 | 0.04 | |
1.14 | 0.09 | 0.10 | 0.09 | 0.11 | |
1.15 | 0.18 | 0.2 | 0.3 | 0.3 | |
1.32 | 0.19 | 0.18 | 0.3 | 0.6 | |
1.28 | 0.17 | 0.12 | 0.2 | 0.2 | |
3.4 | 1.0 | ||||
3.5 | 0.12 | 0.05 | 0.06 | 0.03 | |
1.58 | 0.06 | 0.03 | 0.03 | 0.04 | |
1.59 | 0.11 | <0.1 | <0.1 | <0.1 |
实施例号 | 增殖作用IC50[μM] | ||||
MCF7 | H460 | HCT116 | DU145 | MaTu-ADR | |
3.0 | 0.5 | ||||
3.6 | 0.08 | 0.02 | 0.02 | 0.02 | |
3.7 | 0.1 | <0.1 | <0.1 | <0.1 | |
3.8 | 0.4 | 0.3 | 0.3 | 0.19 | |
3.1 | 0.4 | ||||
1.29 | 0.17 | ||||
1.30 | 0.17 | ||||
3.10 | 0.4 | ||||
3.9 | 1.0 | ||||
1.18 | <0.1 | ||||
1.21 | <0.1 | ||||
1.52 | <0.1 | ||||
1.53 | 0.3 | ||||
1.19 | <0.1 | ||||
1.43 | <0.1 | ||||
1.44 | 0.13 | ||||
WO02/096888中的实施例10 | 0.4 | 0.6 | 0.4 | 0.7 | 0.8 |
实施例号 | CDK2/CycEIC50[nM] | CDK1/CycBIC50[nM] | VEGF-R2IC50[nM] |
2.0 | 16 | 110 | 70 |
1.0 | <10 | 79 | 40 |
1.3 | 6 | 10 | 140 |
1.4 | 10 | 13 | 340 |
1.2 | 20 | 130 | 48 |
2.1 | 390 | >1000 | 74 |
2.3 | 33 | 160 | 61 |
1.23 | 6 | 8 | 75 |
1.24 | 8 | 5 | 150 |
1.25 | 3 | 2 | 70 |
1.31 | 9 | 27 | 140 |
1.41 | 2 | 2 | 76 |
1.42 | 2 | 5 | 64 |
1.7 | >1000 | >1000 | 240 |
1.26 | 4 | 2 | 31 |
1.27 | 4 | 3 | 97 |
1.10 | >1000 | >1000 | 910 |
1.39 | 19 | 49 | 150 |
实施例号 | CDK2/CycEIC50[nM] | CDK1/CycBIC50[nM] | VEGF-R2IC50[nM] |
1.33 | 51 | 200 | 450 |
1.35 | 42 | 96 | 94 |
1.34 | 28 | 110 | 530 |
1.40 | 14 | 21 | 110 |
1.63 | 63 | 200 | 89 |
1.48 | 7 | 16 | 270 |
1.54 | 5 | 8 | 69 |
1.11 | 25 | 44 | 83 |
1.9 | 4 | 5 | 49 |
1.12 | 49 | 160 | 160 |
1.6 | 8 | 14 | 29 |
1.37 | 48 | 63 | 57 |
1.57 | 4 | 8 | 66 |
1.49 | 9 | 15 | 470 |
1.50 | 9 | 44 | 230 |
1.55 | 27 | 45 | 79 |
1.56 | 24 | 68 | 32 |
1.46 | 4 | 11 | 340 |
1.47 | 6 | 27 | 300 |
实施例号 | CDK2/CycEIC50[nM] | CDK1/CycBIC50[nM] | VEGF-R2IC50[nM] |
1.16 | 130 | 170 | 130 |
1.20 | 54 | 160 | 820 |
1.38 | 78 | 75 | 59 |
1.36 | 11 | 43 | 92 |
1.51 | 4 | 5 | 26 |
1.60 | 4 | 4 | 39 |
1.14 | 4 | 7 | 69 |
1.15 | 4 | 25 | 59 |
1.32 | 12 | 16 | 56 |
1.28 | 7 | 14 | 37 |
3.4 | 41 | 72 | 250 |
3.5 | 8 | 17 | 150 |
1.58 | 7 | 4 | 45 |
1.59 | 7 | 9 | 48 |
3.0 | 16 | 49 | 170 |
3.6 | 18 | 22 | 200 |
3.7 | 11 | 19 | 110 |
3.8 | 27 | 91 | >1000 |
3.1 | 33 | 97 | 120 |
实施例号 | CDK2/CycEIC50[nM] | CDK1/CycBIC50[nM] | VEGF-R2IC50[nM] |
1.29 | 4 | 7 | 16 |
1.30 | 6 | 15 | 29 |
3.10 | 4 | 18 | |
3.9 | 8 | 55 | |
1.18 | 3 | 3 | |
1.21 | 6 | 5 | |
1.53 | 4 | 11 | |
1.19 | 3 | 7 | |
1.44 | 2 | 5 | |
WO02/096888中的实施例10 | <10 | 90 | 200 |
实施例号 | 人碳脱水酶-2的抑制作用IC50[nM] |
实施例1.0 | >10000 |
实施例2.0 | >10000 |
乙酰唑胺 | 51 |
WO02/096888中的实施例10 | 190 |
Claims (28)
Applications Claiming Priority (3)
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DE10349423A DE10349423A1 (de) | 2003-10-16 | 2003-10-16 | Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
DE10349423.5 | 2003-10-16 | ||
PCT/EP2004/011661 WO2005037800A1 (de) | 2003-10-16 | 2004-10-12 | Sulfoximinsubstituierte pyrimidine als cdk- und/oder vegf-inhibitoren, deren herstellung und verwendung als arzneimittel |
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CN1867553A true CN1867553A (zh) | 2006-11-22 |
CN1867553B CN1867553B (zh) | 2011-06-08 |
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