CN103204822B - 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 - Google Patents
作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 Download PDFInfo
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- CN103204822B CN103204822B CN201210189086.8A CN201210189086A CN103204822B CN 103204822 B CN103204822 B CN 103204822B CN 201210189086 A CN201210189086 A CN 201210189086A CN 103204822 B CN103204822 B CN 103204822B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000003909 protein kinase inhibitor Substances 0.000 title abstract 3
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title abstract 2
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- 239000011737 fluorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
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- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
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- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 6
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- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
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- 125000000217 alkyl group Chemical group 0.000 description 26
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
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- 125000000753 cycloalkyl group Chemical group 0.000 description 20
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
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- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
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Landscapes
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| CN201210189086.8A CN103204822B (zh) | 2012-01-17 | 2012-06-08 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
| AU2013201455A AU2013201455B8 (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| US14/372,731 US9290468B2 (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| PCT/CN2013/000037 WO2013107283A1 (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| CA2897259A CA2897259C (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| NZ627631A NZ627631A (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| EP13738359.2A EP2804855B1 (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| JP2014551508A JP6077006B2 (ja) | 2012-01-17 | 2013-01-16 | ベンゾ複素環式化合物およびその使用 |
| HK15103824.9A HK1203486B (en) | 2012-01-17 | 2013-01-16 | Benzoheterocyclic compounds and use thereof |
| US15/050,045 US9937158B2 (en) | 2012-01-17 | 2016-02-22 | Benzoheterocyclic compounds and use thereof |
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| CN103204822A CN103204822A (zh) | 2013-07-17 |
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| CN201210189086.8A Active CN103204822B (zh) | 2012-01-17 | 2012-06-08 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
| CN201210190520.4A Active CN103204825B (zh) | 2012-01-17 | 2012-06-08 | 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 |
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| CN104710417B (zh) * | 2013-12-11 | 2020-09-08 | 上海科州药物研发有限公司 | 氮杂吲哚类衍生物及其合成方法 |
| CN105384738B (zh) * | 2014-08-21 | 2017-08-29 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的杂环类化合物及其制备方法和用途 |
| CN105859543A (zh) * | 2016-05-06 | 2016-08-17 | 蚌埠中实化学技术有限公司 | 一种2,6-二氟-4-溴苯甲酰氯的制备方法 |
| CN111205244B (zh) * | 2018-11-22 | 2023-08-18 | 上海科技大学 | 噻唑并环类化合物、其制备方法、中间体和应用 |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN113440616A (zh) * | 2020-03-25 | 2021-09-28 | 上海科州药物研发有限公司 | Ras或raf突变型癌症的联合疗法 |
| EP4663631A1 (en) * | 2023-02-10 | 2025-12-17 | Shanghai Kechow Pharma, Inc. | Polymorph as protein kinase mek inhibitor, and preparation method therefor and use thereof |
| WO2025073765A1 (en) | 2023-10-03 | 2025-04-10 | Institut National de la Santé et de la Recherche Médicale | Methods of prognosis and treatment of patients suffering from melanoma |
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Also Published As
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| WO2013107283A1 (en) | 2013-07-25 |
| CN103204822A (zh) | 2013-07-17 |
| CA2897259A1 (en) | 2013-07-25 |
| AU2013201455B2 (en) | 2015-07-23 |
| US20160235721A1 (en) | 2016-08-18 |
| US9290468B2 (en) | 2016-03-22 |
| CN103204825B (zh) | 2015-03-04 |
| CN103204825A (zh) | 2013-07-17 |
| AU2013201455A8 (en) | 2016-04-14 |
| NZ627631A (en) | 2016-10-28 |
| CN103204827B (zh) | 2014-12-03 |
| HK1203486A1 (en) | 2015-10-30 |
| EP2804855A1 (en) | 2014-11-26 |
| EP2804855B1 (en) | 2017-09-20 |
| JP2015503597A (ja) | 2015-02-02 |
| AU2013201455A1 (en) | 2013-08-01 |
| CA2897259C (en) | 2019-05-07 |
| EP2804855A4 (en) | 2015-07-29 |
| US9937158B2 (en) | 2018-04-10 |
| AU2013201455C1 (en) | 2016-01-21 |
| CN103204827A (zh) | 2013-07-17 |
| US20140371278A1 (en) | 2014-12-18 |
| JP6077006B2 (ja) | 2017-02-08 |
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