JP2020526499A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2020526499A5 JP2020526499A5 JP2019572412A JP2019572412A JP2020526499A5 JP 2020526499 A5 JP2020526499 A5 JP 2020526499A5 JP 2019572412 A JP2019572412 A JP 2019572412A JP 2019572412 A JP2019572412 A JP 2019572412A JP 2020526499 A5 JP2020526499 A5 JP 2020526499A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkoxy
- independently
- cyano
- halo
- 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.)
- Pending
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 167
- -1 chloro, bromo, methyl Chemical group 0.000 claims description 112
- 150000001875 compounds Chemical class 0.000 claims description 98
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 88
- 125000003545 alkoxy group Chemical group 0.000 claims description 82
- 125000005843 halogen group Chemical group 0.000 claims description 68
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 150000002148 esters Chemical class 0.000 claims description 54
- 239000000651 prodrug Substances 0.000 claims description 54
- 229940002612 prodrug Drugs 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 54
- 239000012453 solvate Substances 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 125000002252 acyl group Chemical group 0.000 claims description 37
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000002950 monocyclic group Chemical group 0.000 claims description 24
- 125000002619 bicyclic group Chemical group 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 23
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 16
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 10
- 230000035772 mutation Effects 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 8
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 8
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 8
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 3
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 description 17
- 238000000034 method Methods 0.000 description 13
- 0 CC(C)*1N[C@@](C[C@@](C)I)CC1 Chemical compound CC(C)*1N[C@@](C[C@@](C)I)CC1 0.000 description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 6
- 125000001246 bromo group Chemical group Br* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- 150000003536 tetrazoles Chemical class 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 2
- DFWIEHNMEDMIIL-BYPYZUCNSA-N O[C@@H]1C[IH]CC1 Chemical compound O[C@@H]1C[IH]CC1 DFWIEHNMEDMIIL-BYPYZUCNSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- XFWYMAUDTKMZNM-FNORWQNLSA-N CNCCN(C)c(cc1)cc(OC)c1NC1=NC2C(c(cc3C#N)cc(CC/C=C/C=O)c3NC)=C2CN1 Chemical compound CNCCN(C)c(cc1)cc(OC)c1NC1=NC2C(c(cc3C#N)cc(CC/C=C/C=O)c3NC)=C2CN1 XFWYMAUDTKMZNM-FNORWQNLSA-N 0.000 description 1
- VFFHVTKUQCVAIG-UHFFFAOYSA-N Cc1c[nH]c(c(C#N)c2)c1cc2-c1ccnc(Nc(cc(c(N(C)CCN(C)C)c2)NC(C=C)=O)c2OC)n1 Chemical compound Cc1c[nH]c(c(C#N)c2)c1cc2-c1ccnc(Nc(cc(c(N(C)CCN(C)C)c2)NC(C=C)=O)c2OC)n1 VFFHVTKUQCVAIG-UHFFFAOYSA-N 0.000 description 1
- IKHRSWSIFCXLQZ-UHFFFAOYSA-N Cc1c[nH]c(c(C(N)=O)c2)c1cc2-c1ccnc(Nc(cc(c(N(C)CCN(C)C)c2)NC(C=C)=O)c2OC)n1 Chemical compound Cc1c[nH]c(c(C(N)=O)c2)c1cc2-c1ccnc(Nc(cc(c(N(C)CCN(C)C)c2)NC(C=C)=O)c2OC)n1 IKHRSWSIFCXLQZ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000005961 oxazepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000005475 oxolanyl group Chemical group 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762528697P | 2017-07-05 | 2017-07-05 | |
| US62/528,697 | 2017-07-05 | ||
| PCT/US2018/040904 WO2019010295A1 (en) | 2017-07-05 | 2018-07-05 | SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF EGFR TYROSINE KINASE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020526499A JP2020526499A (ja) | 2020-08-31 |
| JP2020526499A5 true JP2020526499A5 (enExample) | 2021-07-26 |
Family
ID=64950363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019572412A Pending JP2020526499A (ja) | 2017-07-05 | 2018-07-05 | Ｅｇｆｒチロシンキナーゼの臨床上重要な突然変異体の選択的阻害剤 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20200131176A1 (enExample) |
| EP (1) | EP3648753A4 (enExample) |
| JP (1) | JP2020526499A (enExample) |
| KR (1) | KR20200028966A (enExample) |
| CN (1) | CN111093645A (enExample) |
| CA (1) | CA3068854A1 (enExample) |
| WO (1) | WO2019010295A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI726968B (zh) | 2016-01-07 | 2021-05-11 | 開曼群島商Ｃｓ醫藥技術公司 | Egfr酪胺酸激酶之臨床重要突變體之選擇性抑制劑 |
| CN108707139B (zh) * | 2017-06-13 | 2021-04-06 | 北京鞍石生物科技有限责任公司 | 氨基嘧啶类化合物及其制备方法和应用 |
| CN111566100B (zh) * | 2018-02-12 | 2023-10-27 | 恩瑞生物医药科技（上海）有限公司 | 嘧啶类化合物、其制备方法及其医药用途 |
| AU2020240382B2 (en) * | 2019-03-19 | 2022-08-25 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| EP3942045A1 (en) | 2019-03-21 | 2022-01-26 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| CN111747950B (zh) * | 2019-03-29 | 2024-01-23 | 深圳福沃药业有限公司 | 用于治疗癌症的嘧啶衍生物 |
| US12523663B2 (en) | 2019-06-04 | 2026-01-13 | Inserm (Institut National De La Santé Et De La Rescherche Médicale) | Use of CD9 as a biomarker and as a biotarget in glomerulonephritis or glomerulosclerosis |
| MX2022003769A (es) | 2019-10-03 | 2022-04-20 | Bristol Myers Squibb Co | Indazol carboxamidas como inhibidores de cinasas. |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| CN113179640B (zh) * | 2019-11-26 | 2024-06-25 | 上海翰森生物医药科技有限公司 | 含氮多环类衍生物抑制剂、其制备方法和应用 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| WO2021243596A1 (en) * | 2020-06-03 | 2021-12-09 | InventisBio Co., Ltd. | Aminopyrimidine compounds, preparation methods and uses thereof |
| KR20220085735A (ko) * | 2020-12-14 | 2022-06-22 | 보로노이바이오 주식회사 | 아이소옥사졸리딘 유도체 화합물 및 이의 용도 |
| EP4330256A4 (en) * | 2021-04-30 | 2025-03-05 | Suzhou Puhe Biopharma Co., Ltd. | PYRIMIDINYLAMINOBENZOLES FOR THE TREATMENT OF LUNG CANCER |
| AU2022271388A1 (en) | 2021-05-17 | 2022-12-01 | Voronoi Inc. | Heteroaryl derivative compounds, and uses thereof |
| CN113651800B (zh) * | 2021-09-07 | 2022-08-19 | 山东铂源药业股份有限公司 | 一种甲磺酸奥希替尼的制备方法 |
| CN115650974B (zh) * | 2022-08-04 | 2024-06-18 | 天津大学 | N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-顺式戊二烯酰胺衍生物及应用 |
| WO2024094064A1 (en) * | 2022-11-02 | 2024-05-10 | Suzhou Puhe Biopharma Co., Ltd | Pyrimidinylaminobenzenes for treating lung cancer with distant metastasis |
| EP4612147A1 (en) * | 2022-11-03 | 2025-09-10 | Voronoi Inc. | Fumarate, tartrate, malate, and citrate salts of an egfr inhibitor |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ603525A (en) * | 2008-06-27 | 2015-02-27 | Celgene Avilomics Res Inc | Pyrimidine based compound and uses thereof |
| CN104860941B (zh) * | 2014-02-25 | 2017-03-22 | 上海海雁医药科技有限公司 | 2,4‑二取代苯‑1,5‑二胺衍生物及其应用以及由其制备的药物组合物和药用组合物 |
| US10266517B2 (en) * | 2014-12-23 | 2019-04-23 | Dana-Farber Cancer Institute, Inc. | Pyrimidines as EGFR inhibitors and methods of treating disorders |
| TWI726968B (zh) * | 2016-01-07 | 2021-05-11 | 開曼群島商Ｃｓ醫藥技術公司 | Egfr酪胺酸激酶之臨床重要突變體之選擇性抑制劑 |
| CN110818690B (zh) * | 2016-07-26 | 2021-08-10 | 深圳市塔吉瑞生物医药有限公司 | 用于抑制蛋白酪氨酸激酶活性的氨基嘧啶类化合物 |
-
2018
- 2018-07-05 KR KR1020207003387A patent/KR20200028966A/ko not_active Withdrawn
- 2018-07-05 WO PCT/US2018/040904 patent/WO2019010295A1/en not_active Ceased
- 2018-07-05 EP EP18827860.0A patent/EP3648753A4/en not_active Withdrawn
- 2018-07-05 US US16/628,831 patent/US20200131176A1/en not_active Abandoned
- 2018-07-05 JP JP2019572412A patent/JP2020526499A/ja active Pending
- 2018-07-05 CN CN201880044480.8A patent/CN111093645A/zh active Pending
- 2018-07-05 CA CA3068854A patent/CA3068854A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2019501222A5 (enExample) | ||
| AU2020200407B2 (en) | Tetrahydro-pyrido[3,4-b]indole estrogen receptor modulators and uses thereof | |
| TWI794190B (zh) | 含有取代的吡啶酮之三環化合物及其使用方法 | |
| JP7355741B2 (ja) | ベンズアミド化合物 | |
| CA2407593C (en) | Fused heteroaryl derivatives | |
| US6608056B1 (en) | Fused heteroaryl derivatives | |
| US20220363666A1 (en) | Tyrosine kinase inhibitor compositions, methods of making and methods of use | |
| DE60022893T2 (de) | Naphthyridinverbindungen | |
| KR101893627B1 (ko) | 티아졸 유도체 | |
| US20150065525A1 (en) | Methods for improving diaphragm function | |
| JP2018531983A (ja) | タンパク質分解誘導キメラ化合物ならびにその調製方法および使用方法 | |
| CN107548394A (zh) | 调节激酶的化合物的固体形式 | |
| JP2013539777A5 (enExample) | ||
| RU2013151803A (ru) | Бициклические гетероциклические соединения и их применения в терапии | |
| HRP20231533T1 (hr) | Kristalni oblici od (s)-1-(4-fluorofenil)-1-(2-(4-(6-(1-metil-1h-pirazol-4-il)pirolo[2,1-f][1,2,4 ]triazin-4-il)piperazinil)-pirimidin-5-il)etan-1-amina i postupci priprave | |
| TWI801517B (zh) | 經取代的2-吡啶酮三環化合物、其類似物及其使用方法 | |
| RU2014151009A (ru) | Пиразолопиримидоновые и пиразолопиридоновые ингибиторы танкиразы | |
| EA012110B1 (ru) | Пирролодигидроизохинолины как ингибиторы pde10 | |
| RU2012113128A (ru) | Производные имидазопиридина или имидазопиримидина в качестве ингибиторов фосфодиэстеразы 10а | |
| JP2009511628A (ja) | Ｆｌｔ３キナーゼの阻害方法 | |
| EP4323349A1 (en) | Isoindolinone amide compounds useful to treat diseases associated with gspt1 | |
| AU2022201717B2 (en) | Treatment of cancer | |
| JP2018501315A5 (enExample) | ||
| CN109906224A (zh) | 三唑吡啶化合物及其应用 | |
| CN108884067A (zh) | 可用于治疗癌症和糖尿病的6-杂环基-4-吗啉-4-基吡啶-2-酮化合物 |