CN100575341C - 四氢吲哚酮的衍生物和四氢吲唑酮的衍生物及它们的应用 - Google Patents
四氢吲哚酮的衍生物和四氢吲唑酮的衍生物及它们的应用 Download PDFInfo
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- CN100575341C CN100575341C CN200610087495A CN200610087495A CN100575341C CN 100575341 C CN100575341 C CN 100575341C CN 200610087495 A CN200610087495 A CN 200610087495A CN 200610087495 A CN200610087495 A CN 200610087495A CN 100575341 C CN100575341 C CN 100575341C
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- China
- Prior art keywords
- oxygen
- trimethylammonium
- benzamide
- tetrahydrochysene indazole
- piperidines
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- QPNLUIFEKCYQHR-UHFFFAOYSA-N 1,2,3a,4-tetrahydroindazol-3-one Chemical class C1=CCC2C(=O)NNC2=C1 QPNLUIFEKCYQHR-UHFFFAOYSA-N 0.000 title description 8
- YJJUTLWYXYQJNJ-UHFFFAOYSA-N 1,3,3a,4-tetrahydroindol-2-one Chemical class C1C=CC=C2NC(=O)CC21 YJJUTLWYXYQJNJ-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 584
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 288
- IDDAQARKHUGOPH-UHFFFAOYSA-N benzene oxalonitrile Chemical compound C1=CC=CC=C1.N#CC#N IDDAQARKHUGOPH-UHFFFAOYSA-N 0.000 claims description 124
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 114
- -1 ethyl carbamyl Chemical group 0.000 claims description 97
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 54
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 49
- 150000003053 piperidines Chemical class 0.000 claims description 45
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 125000003282 alkyl amino group Chemical group 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- STWODXDTKGTVCJ-UHFFFAOYSA-N 4-pyrrolidin-1-ylpiperidine Chemical class C1CCCN1C1CCNCC1 STWODXDTKGTVCJ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 8
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- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 claims description 7
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- 229910052799 carbon Inorganic materials 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
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- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
- 150000003217 pyrazoles Chemical class 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
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- 150000003016 phosphoric acids Chemical class 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- IYPZRUYMFDWKSS-UHFFFAOYSA-N piperazin-1-amine Chemical group NN1CCNCC1 IYPZRUYMFDWKSS-UHFFFAOYSA-N 0.000 claims 1
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CN101273991B (zh) * | 2007-03-28 | 2010-05-26 | 广东同德药业有限公司 | 四氢吲哚酮/四氢吲唑酮/四氢咔唑衍生物及其盐在制备抗病毒药物中的应用 |
CN101481353B (zh) * | 2008-01-08 | 2011-07-20 | 广东同德药业有限公司 | 四氢吲唑酮或四氢吲哚酮取代的吲唑衍生物及其盐 |
CN102311389A (zh) * | 2010-06-29 | 2012-01-11 | 王小龙 | 一种氮芳香取代吡唑衍生物、及其合成和抗癌应用 |
CN101955461B (zh) * | 2010-10-08 | 2012-11-21 | 广州暨南生物医药研究开发基地有限公司 | 一种Hsp90抑制剂Xbj-B11及其制备方法与应用 |
CN101967125B (zh) * | 2010-10-08 | 2012-07-04 | 广州暨南生物医药研究开发基地有限公司 | 一种Hsp90抑制剂Xbj-B16-1及其制备方法与应用 |
CN102816150B (zh) * | 2012-09-07 | 2014-02-12 | 河南师范大学 | 具有抑菌活性的吲哚及其衍生物-三氮唑类化合物及其制备方法 |
CN103467356B (zh) * | 2013-08-12 | 2015-04-01 | 绍兴文理学院 | 一种四氢吲哚化合物及其制备方法与应用 |
CN103784437A (zh) * | 2014-01-02 | 2014-05-14 | 暨南大学 | Hsp90抑制剂在制备肿瘤多药耐药性逆转剂中的应用 |
US10246421B2 (en) | 2014-09-11 | 2019-04-02 | Esanex, Inc. | Indazolyl- and indolyl-benzamide derivatives |
CN104592203A (zh) * | 2015-01-30 | 2015-05-06 | 广州暨南生物医药研究开发基地有限公司 | 一种2-氨基-4-四氢吲唑取代的苯甲酰胺化合物及其在制备抗肿瘤药物中的应用 |
CN104592230B (zh) * | 2015-01-30 | 2017-02-01 | 广州暨南生物医药研究开发基地有限公司 | 一种2‑(石榴皮烷‑3‑氨基)‑4‑四氢吲唑取代的苯甲酰胺化合物及其应用 |
CN105693819B (zh) * | 2016-03-10 | 2019-06-18 | 三峡大学 | 一种四氢吲哚-4酮三肽类化合物,制备方法及其在抗肿瘤药物中的用途 |
CN114213332B (zh) * | 2022-02-21 | 2022-05-17 | 深圳市人民医院 | 一种四氢吲唑类化合物及其制备方法和应用 |
CN116444438B (zh) * | 2023-04-17 | 2024-02-13 | 深圳市人民医院 | 一种苯甲酰胺类化合物及其制备方法、使用方法和应用 |
CN116554105B (zh) * | 2023-04-26 | 2024-02-20 | 深圳市人民医院 | 苯甲酰胺类化合物及制备方法、使用方法和应用 |
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