CN103467482A - 稠合嘧啶类化合物,其制备方法,中间体,组合物和应用 - Google Patents
稠合嘧啶类化合物,其制备方法,中间体,组合物和应用 Download PDFInfo
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- CN103467482A CN103467482A CN2013101222601A CN201310122260A CN103467482A CN 103467482 A CN103467482 A CN 103467482A CN 2013101222601 A CN2013101222601 A CN 2013101222601A CN 201310122260 A CN201310122260 A CN 201310122260A CN 103467482 A CN103467482 A CN 103467482A
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- alkyl
- compound
- heterocyclic radical
- solvate
- prodrug
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- -1 pyrimidine compound Chemical class 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 title abstract description 29
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- 239000012453 solvate Substances 0.000 claims abstract description 38
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 124
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 77
- 150000003254 radicals Chemical class 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 125000005842 heteroatom Chemical group 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 33
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- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 15
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- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 15
- 125000005418 aryl aryl group Chemical group 0.000 claims description 14
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- A61P3/00—Drugs for disorders of the metabolism
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Abstract
Description
化合物编号 | IC50on PI3Kα(nM) | IC50on PI3Kδ(nM) |
1 | 9.5 | 18 |
6 | 57 | 62 |
11 | 13.1 | 28.3 |
12 | 232 | 190 |
13 | 265 | 327 |
15 | 104 | 200 |
17 | 245 | 65.4 |
18 | 12.0 | 12.6 |
19 | 51.4 | 31.9 |
20 | 46.2 | 52.0 |
21 | 35 | 4.7 |
22 | 77 | 11 |
23 | 202 | 16 |
24 | 18.9 | 8.3 |
25 | 56 | 13 |
26 | 141 | 41 |
27 | 76 | 18 |
28 | 24 | 38 |
29 | 18 | 7 |
30 | 262.2 | 60.4 |
31 | 26 | 290 |
32 | 32 | 137 |
36 | 157 | 56 |
化合物编号 | A549(IC50,μM) | PC3(IC50,μM) | U87-MG(IC50,μM) |
1 | 2.9944 | 3.1394 | 6.5683 |
6 | 4.6422 | 6.1073 | 7.4109 |
11 | 6.4383 | 10.098 | 12.1719 |
17 | 4.8164 | 5.3876 | 7.8122 |
18 | 3.637 | 2.3144 | 8.8724 |
19 | 3.9947 | 2.6073 | 8.078 |
24 | 2.7395 | 2.0674 | 9.3573 |
25 | 6.6843 | 3.0606 | 11.2905 |
26 | 9.3333 | 3.2792 | 19.7315 |
28 | 2.5991 | 1.9357 | 4.4577 |
29 | 2.7024 | 1.4867 | 3.7358 |
Claims (36)
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EP (1) | EP2860181B1 (zh) |
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Cited By (4)
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US9499561B2 (en) | 2012-04-10 | 2016-11-22 | Shanghai Yingli Pharmaceutical Co., Ltd. | Fused pyrimidine compound, and preparation method, intermediate, composition, and uses thereof |
CN106632443A (zh) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | 一种2‑氨基嘧啶‑5‑硼酸频哪酯硼酸盐的合成方法 |
CN104513254B (zh) * | 2013-09-30 | 2019-07-26 | 上海璎黎药业有限公司 | 稠合嘧啶类化合物、中间体、其制备方法、组合物和应用 |
CN112047939A (zh) * | 2019-06-06 | 2020-12-08 | 江苏先声药业有限公司 | 一种具有抗肿瘤活性的四氢吡啶并嘧啶类化合物 |
Families Citing this family (3)
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SG11201602446VA (en) | 2013-10-16 | 2016-05-30 | Shanghai Yingli Pharm Co Ltd | Fused heterocyclic compound, preparation method therefor, pharmaceutical composition, and uses thereof |
CN106279201A (zh) * | 2015-05-15 | 2017-01-04 | 上海睿智化学研究有限公司 | 一种稠合嘧啶类衍生物马来酸盐、晶体、制备方法及应用 |
US20230079863A1 (en) * | 2021-03-29 | 2023-03-16 | Gilead Sciences, Inc. | Khk inhibitors |
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US9499561B2 (en) | 2012-04-10 | 2016-11-22 | Shanghai Yingli Pharmaceutical Co., Ltd. | Fused pyrimidine compound, and preparation method, intermediate, composition, and uses thereof |
CN104513254B (zh) * | 2013-09-30 | 2019-07-26 | 上海璎黎药业有限公司 | 稠合嘧啶类化合物、中间体、其制备方法、组合物和应用 |
CN106632443A (zh) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | 一种2‑氨基嘧啶‑5‑硼酸频哪酯硼酸盐的合成方法 |
CN106632443B (zh) * | 2016-11-23 | 2022-06-17 | 山东友帮生化科技有限公司 | 一种2-氨基嘧啶-5-硼酸频哪酯硼酸盐的合成方法 |
CN112047939A (zh) * | 2019-06-06 | 2020-12-08 | 江苏先声药业有限公司 | 一种具有抗肿瘤活性的四氢吡啶并嘧啶类化合物 |
CN112047939B (zh) * | 2019-06-06 | 2023-05-02 | 江苏先声药业有限公司 | 一种具有抗肿瘤活性的四氢吡啶并嘧啶类化合物 |
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