JP6505131B2 - イミダゾ［４，５−ｃ］キノリン−２−オン化合物および癌の処置におけるそれらの使用 - Google Patents
イミダゾ［４，５−ｃ］キノリン−２−オン化合物および癌の処置におけるそれらの使用 Download PDFInfo
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- JP6505131B2 JP6505131B2 JP2016567002A JP2016567002A JP6505131B2 JP 6505131 B2 JP6505131 B2 JP 6505131B2 JP 2016567002 A JP2016567002 A JP 2016567002A JP 2016567002 A JP2016567002 A JP 2016567002A JP 6505131 B2 JP6505131 B2 JP 6505131B2
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- JP
- Japan
- Prior art keywords
- methyl
- imidazo
- quinolin
- pyridin
- fluoro
- 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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- 238000011282 treatment Methods 0.000 title claims description 64
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 631
- 150000001875 compounds Chemical class 0.000 claims description 216
- -1 1-methoxy-cyclobut-3-yl Chemical group 0.000 claims description 178
- 150000003839 salts Chemical class 0.000 claims description 153
- 239000001257 hydrogen Substances 0.000 claims description 61
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 59
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
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- 125000002393 azetidinyl group Chemical group 0.000 claims description 11
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- 229960005243 carmustine Drugs 0.000 claims description 10
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 10
- 229960004630 chlorambucil Drugs 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 10
- 229960001924 melphalan Drugs 0.000 claims description 10
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 9
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- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 9
- DWICJHMMZLNUEB-UHFFFAOYSA-N COC1CC(C1)n1c2c(cnc3ccc(cc23)-c2ccc(OCCCN(C)C)nc2)n(C)c1=O Chemical compound COC1CC(C1)n1c2c(cnc3ccc(cc23)-c2ccc(OCCCN(C)C)nc2)n(C)c1=O DWICJHMMZLNUEB-UHFFFAOYSA-N 0.000 claims description 8
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 8
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 8
- BKWJAKQVGHWELA-UHFFFAOYSA-N 1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methyl-1-piperazinyl)anilino]-2-prop-2-enyl-3-pyrazolo[3,4-d]pyrimidinone Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)N(CC=C)N(C=3N=C(C=CC=3)C(C)(C)O)C2=N1 BKWJAKQVGHWELA-UHFFFAOYSA-N 0.000 claims description 7
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 7
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 7
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 7
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 claims description 7
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- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 claims description 7
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- 239000000126 substance Substances 0.000 claims description 7
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 6
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- OHUHVTCQTUDPIJ-JYCIKRDWSA-N ceralasertib Chemical compound C[C@@H]1COCCN1C1=CC(C2(CC2)[S@](C)(=N)=O)=NC(C=2C=3C=CNC=3N=CC=2)=N1 OHUHVTCQTUDPIJ-JYCIKRDWSA-N 0.000 claims description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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| PCT/GB2015/051312 WO2015170081A1 (en) | 2014-05-08 | 2015-05-05 | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
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| CA2981365A1 (en) * | 2015-04-02 | 2016-10-06 | Merck Patent Gmbh | Imidazolonylquinolines and the use thereof as atm kinase inhibitors |
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| GB201519406D0 (en) * | 2015-11-03 | 2015-12-16 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| GB201519568D0 (en) * | 2015-11-05 | 2015-12-23 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| EP4071174A1 (en) * | 2016-02-15 | 2022-10-12 | AstraZeneca AB | Methods comprising fixed intermittent dosing of cediranib |
| WO2017162605A1 (en) * | 2016-03-21 | 2017-09-28 | Astrazeneca Ab | Cinnolin-4-amine compounds and their use in treating cancer |
| US20190119270A1 (en) | 2016-04-07 | 2019-04-25 | Astrazeneca Ab | N-Oxide Compound and Its Use in Treating Cancer |
| GB201608227D0 (en) * | 2016-05-11 | 2016-06-22 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| HUE054548T2 (hu) | 2016-12-20 | 2021-09-28 | Astrazeneca Ab | Amino-triazolopiridin vegyületek és azok alkalmazása rák kezelésében |
| CN110167941B (zh) * | 2017-01-09 | 2023-04-04 | 上海瑛派药业有限公司 | 取代的稠合杂芳基化合物作为激酶抑制剂及其应用 |
| CN106798741A (zh) * | 2017-02-07 | 2017-06-06 | 宫英 | 一种治疗抑郁症的药物组合物 |
| CN106692147A (zh) * | 2017-02-07 | 2017-05-24 | 李明英 | 一种治疗男性不育的药物组合物 |
| CN106822123A (zh) * | 2017-02-09 | 2017-06-13 | 王艳苓 | 一种治疗心脑血管疾病的药物组合物 |
| WO2018153365A1 (zh) | 2017-02-27 | 2018-08-30 | 上海瑛派药业有限公司 | 取代的稠合杂芳三环化合物作为激酶抑制剂及其应用 |
| JOP20190209A1 (ar) * | 2017-03-16 | 2019-09-12 | Astrazeneca Ab | مركبات إيميدازو [ 4، 5-c ] كينولين-2-أون ديوترومية واستخدامها في علاج السرطان |
| WO2019057757A1 (en) | 2017-09-20 | 2019-03-28 | Astrazeneca Ab | 1,3-DIHYDROIMIDAZO [4,5-C] CINNOLIN-2-ONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER |
| CN110386932A (zh) * | 2018-04-20 | 2019-10-29 | 艾科思莱德制药公司 | 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 |
| WO2019201283A1 (en) * | 2018-04-20 | 2019-10-24 | Xrad Therapeutics, Inc. | Dual atm and dna-pk inhibitors for use in anti-tumor therapy |
| CN115636833B (zh) * | 2018-09-14 | 2024-11-29 | 苏州赞荣医药科技有限公司 | 作为ATM激酶选择性调节剂的取代的咪唑并[4,5-c]噌啉-2-酮化合物及其用途 |
| EP3866785A1 (en) * | 2018-10-15 | 2021-08-25 | Merck Patent GmbH | Combination therapy utilizing dna alkylating agents and atr inhibitors |
| EP3935060B1 (en) * | 2019-03-05 | 2023-11-15 | Astrazeneca AB | Fused tricyclic compounds useful as anticancer agents |
| TW202102497A (zh) * | 2019-03-29 | 2021-01-16 | 瑞典商阿斯特捷利康公司 | 化合物及它們在治療癌症中之用途 |
| CN111909147B (zh) * | 2019-05-10 | 2021-07-20 | 山东轩竹医药科技有限公司 | Dna-pk抑制剂 |
| CN114026097B (zh) * | 2019-07-10 | 2024-02-23 | 上海瑛派药业有限公司 | 取代的吡唑并喹唑啉酮化合物及其应用 |
| US20220354859A1 (en) * | 2019-09-12 | 2022-11-10 | Impact Therapeutics (Shanghai), Inc | Substituted imidazoquinoxaline compounds and uses thereof |
| WO2021139814A1 (zh) * | 2020-01-09 | 2021-07-15 | 南京明德新药研发有限公司 | 喹啉并咪唑类化合物及其应用 |
| CN114980900A (zh) * | 2020-01-13 | 2022-08-30 | 上海华禹生物科技有限公司 | N2-喹啉或异喹啉取代的嘌呤衍生物在癌症治疗中的用途 |
| JP2023539715A (ja) * | 2020-06-24 | 2023-09-19 | アストラゼネカ ユーケー リミテッド | 抗体－薬物コンジュゲートとａｔｍ阻害剤との組合わせ |
| EP3992191A1 (en) | 2020-11-03 | 2022-05-04 | Deutsches Krebsforschungszentrum | Imidazo[4,5-c]quinoline compounds and their use as atm kinase inhibitors |
| CN117015534A (zh) * | 2021-02-03 | 2023-11-07 | 艾科思莱德制药公司 | 用于癌症疗法的双重atm和dna-pk抑制剂以及免疫治疗剂的组合 |
| AU2021433713A1 (en) * | 2021-03-17 | 2023-09-28 | Suzhou Zanrong Pharma Limited | Selective modulators of ataxia telangiectasia mutated (atm) kinase and uses thereof |
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| GB0211649D0 (en) * | 2002-05-21 | 2002-07-03 | Novartis Ag | Organic compounds |
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| GB0510390D0 (en) * | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
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| TW201041888A (en) * | 2009-05-06 | 2010-12-01 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| US20100311714A1 (en) * | 2009-06-04 | 2010-12-09 | Pascal Furet | 1H-IMIDAZO[4,5-c]QUINOLINONE COMPOUNDS |
| EA020715B1 (ru) | 2009-06-04 | 2015-01-30 | Новартис Аг | ПРОИЗВОДНЫЕ 1H-ИМИДАЗО[4,5-c]ХИНОЛИНОНА |
| AU2010299820A1 (en) * | 2009-09-28 | 2012-04-19 | F. Hoffmann-La Roche Ag | Benzoxepin PI3K inhibitor compounds and methods of use |
| GB0919423D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
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| CN102399218A (zh) * | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
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| JP6042060B2 (ja) * | 2011-09-26 | 2016-12-14 | サノフイ | ピラゾロキノリノン誘導体、その調製および治療上の使用 |
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