RU2689158C2 - Новое хинолин-замещенное соединение - Google Patents
Новое хинолин-замещенное соединение Download PDFInfo
- Publication number
- RU2689158C2 RU2689158C2 RU2016110096A RU2016110096A RU2689158C2 RU 2689158 C2 RU2689158 C2 RU 2689158C2 RU 2016110096 A RU2016110096 A RU 2016110096A RU 2016110096 A RU2016110096 A RU 2016110096A RU 2689158 C2 RU2689158 C2 RU 2689158C2
- Authority
- RU
- Russia
- Prior art keywords
- amino
- quinolin
- formula
- compound
- methylene
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 320
- -1 C-C-alkyl group Chemical group 0.000 claims abstract description 139
- 102000001301 EGF receptor Human genes 0.000 claims abstract description 103
- 108060006698 EGF receptor Proteins 0.000 claims abstract description 103
- 150000003839 salts Chemical class 0.000 claims abstract description 65
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 44
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 41
- 230000000694 effects Effects 0.000 claims abstract description 35
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 32
- 201000011510 cancer Diseases 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 13
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims abstract description 12
- 125000002817 1-piperidinomethyl group Chemical group [H]C([H])([*])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 9
- 229910052796 boron Inorganic materials 0.000 claims abstract description 9
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 4
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000004305 biphenyl Substances 0.000 claims abstract description 3
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 239000001301 oxygen Chemical group 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims description 96
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 86
- 238000000034 method Methods 0.000 claims description 74
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229940121647 egfr inhibitor Drugs 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- XGSYUTSLKZLTRT-MWWKQMNYSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(\C=C/Cl)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(\C=C/Cl)=O)=C)C=1C=NC2=CC=CC=C2C=1 XGSYUTSLKZLTRT-MWWKQMNYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- QFWKCLYABFSKKQ-MBNRZODZSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(\C=C\CN(C)C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(\C=C\CN(C)C)=O)=C)C=1C=NC2=CC=CC=C2C=1 QFWKCLYABFSKKQ-MBNRZODZSA-N 0.000 claims description 7
- NYZLBECBOHTDFP-MRXNPFEDSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 NYZLBECBOHTDFP-MRXNPFEDSA-N 0.000 claims description 6
- XGSYUTSLKZLTRT-FYCOFBDGSA-N (e)-n-[(7s)-4-amino-6-methylidene-5-quinolin-3-yl-7,8-dihydropyrimido[5,4-b]pyrrolizin-7-yl]-3-chloroprop-2-enamide Chemical compound C1=CC=CC2=CC(C3=C4C(=C)[C@H](NC(=O)\C=C\Cl)CN4C=4N=CN=C(C3=4)N)=CN=C21 XGSYUTSLKZLTRT-FYCOFBDGSA-N 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- BBTMYZZONHFZFE-QGZVFWFLSA-N N-[(7S)-4-amino-6-methylidene-5-quinolin-3-yl-7,8-dihydropyrimido[5,4-b]pyrrolizin-7-yl]but-2-enamide Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C=CC)=O)=C)C=1C=NC2=CC=CC=C2C=1 BBTMYZZONHFZFE-QGZVFWFLSA-N 0.000 claims description 3
- RLMXXZGDSAUHHX-MRXNPFEDSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C#C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C#C)=O)=C)C=1C=NC2=CC=CC=C2C=1 RLMXXZGDSAUHHX-MRXNPFEDSA-N 0.000 claims description 3
- OQNFSNAPCNWXFE-QGZVFWFLSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C(=C)C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C(=C)C)=O)=C)C=1C=NC2=CC=CC=C2C=1 OQNFSNAPCNWXFE-QGZVFWFLSA-N 0.000 claims description 3
- GXMBFEMPGWKDHV-PVQCJRHBSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C=C)=O)C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CN21)NC(C=C)=O)C)C=1C=NC2=CC=CC=C2C=1 GXMBFEMPGWKDHV-PVQCJRHBSA-N 0.000 claims description 3
- NYZLBECBOHTDFP-INIZCTEOSA-N NC1=NC=NC2=C1C(=C1C([C@H](CN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@H](CN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 NYZLBECBOHTDFP-INIZCTEOSA-N 0.000 claims description 3
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- PNBVXUUHQRNXEH-MRXNPFEDSA-N NC1=NC=NC2=C1C(=C1C([C@@H](CCN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C([C@@H](CCN21)NC(C=C)=O)=C)C=1C=NC2=CC=CC=C2C=1 PNBVXUUHQRNXEH-MRXNPFEDSA-N 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- HOMUIRDLUGQYFH-UHFFFAOYSA-N 3h-pyrrolo[1,2-a]azepine Chemical compound C1=CC=CN2CC=CC2=C1 HOMUIRDLUGQYFH-UHFFFAOYSA-N 0.000 claims 1
- MKCYPWYURWOKST-INIZCTEOSA-N NC1=NC=NC2=C1C(=C1C(=C[C@@H](CN21)NC(C=C)=O)C)C=1C=NC2=CC=CC=C2C=1 Chemical compound NC1=NC=NC2=C1C(=C1C(=C[C@@H](CN21)NC(C=C)=O)C)C=1C=NC2=CC=CC=C2C=1 MKCYPWYURWOKST-INIZCTEOSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- 238000003786 synthesis reaction Methods 0.000 description 90
- 230000015572 biosynthetic process Effects 0.000 description 88
- 239000000243 solution Substances 0.000 description 73
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 69
- 239000002904 solvent Substances 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
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- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 63
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- 230000002829 reductive effect Effects 0.000 description 40
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- 239000003054 catalyst Substances 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
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- 108091000080 Phosphotransferase Proteins 0.000 description 29
- 102000020233 phosphotransferase Human genes 0.000 description 29
- 238000002955 isolation Methods 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000007864 aqueous solution Substances 0.000 description 26
- 238000001816 cooling Methods 0.000 description 26
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
- 125000006239 protecting group Chemical group 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 23
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
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- 238000002425 crystallisation Methods 0.000 description 18
- 230000008025 crystallization Effects 0.000 description 18
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 18
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- 229920006395 saturated elastomer Polymers 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- 238000009835 boiling Methods 0.000 description 14
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- AISKGLQBMYTNSW-JTQLQIEISA-N tert-butyl n-[(3r)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)pent-1-en-3-yl]carbamate Chemical compound N1=CN=C2N(CC[C@@H](NC(=O)OC(C)(C)C)C=C)C=C(I)C2=C1N AISKGLQBMYTNSW-JTQLQIEISA-N 0.000 description 1
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- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- HHBXWXJLQYJJBW-UHFFFAOYSA-M triphenyl(propan-2-yl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C)C)C1=CC=CC=C1 HHBXWXJLQYJJBW-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D471/12—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 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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| PCT/JP2014/071951 WO2015025936A1 (ja) | 2013-08-22 | 2014-08-22 | 新規キノリン置換化合物 |
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| TW (1) | TWI603971B (https=) |
| WO (1) | WO2015025936A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| BR112016003247B1 (pt) * | 2013-08-22 | 2022-05-10 | Taiho Pharmaceutical Co., Ltd | Composto substituído por quinolina, composição farmacêutica compreendendo o referido composto e seu uso |
| WO2018079310A1 (ja) * | 2016-10-31 | 2018-05-03 | 大鵬薬品工業株式会社 | エクソン２０挿入変異型ｅｇｆｒ選択的阻害剤 |
| KR102771603B1 (ko) * | 2016-11-17 | 2025-02-24 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | Egfr 또는 her2 엑손 20 돌연변이를 갖는 암 세포에 대한 항종양 활성을 갖는 화합물 |
| CN108101905A (zh) * | 2016-11-24 | 2018-06-01 | 中国科学院上海药物研究所 | 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 |
| FR3068971B1 (fr) * | 2017-07-12 | 2019-08-30 | Protneteomix | Acides 5-{4-allyl-5-[2-(4-alcoxyphenyl)quinolein-4-yl]-4h-1,2,4-triazole-3-ylsulphanylmethyl}furan-2-carboxyliques dans le traitement du cancer |
| PL3677266T3 (pl) * | 2017-09-01 | 2024-07-01 | Taiho Pharmaceutical Co., Ltd. | Selektywny inhibitor egfr z mutacją w eksonie 18 i/lub eksonie 21 |
| ES3033635T3 (en) * | 2018-12-28 | 2025-08-06 | Taiho Pharmaceutical Co Ltd | L718 and/or l792 mutant treatment-resistant egfr inhibitor for use in the treatment of cancer |
| PT3943491T (pt) | 2019-03-19 | 2025-07-28 | Voronoi Inc | Derivado de heteroarilo, método para a produção do mesmo e composição farmacêutica que compreende o mesmo como componente eficaz |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| CN115181104A (zh) * | 2019-09-29 | 2022-10-14 | 深圳市塔吉瑞生物医药有限公司 | 取代的稠合三环衍生物及其组合物及用途 |
| WO2021127456A1 (en) | 2019-12-19 | 2021-06-24 | Rain Therapeutics Inc. | Methods of inhibiting epidermal growth factor receptor proteins |
| CN113861195B (zh) * | 2020-06-30 | 2022-11-18 | 上海和誉生物医药科技有限公司 | 一种多稠环egfr抑制剂及其制备方法和应用 |
| CN116096372B (zh) * | 2020-07-09 | 2024-09-03 | 上海和誉生物医药科技有限公司 | 一种egfr抑制剂、其制备方法和在药学上的应用 |
| WO2022055895A1 (en) * | 2020-09-08 | 2022-03-17 | Cullinan Pearl Corp. | Treatment regimens for exon-20 insertion mutant egfr cancers |
| WO2022121967A1 (zh) * | 2020-12-09 | 2022-06-16 | 南京药石科技股份有限公司 | Egfr酪氨酸激酶抑制剂及其用途 |
| TW202309022A (zh) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | 用於治療具egfr突變之癌症之胺基取代雜環 |
| CN117479943A (zh) | 2021-06-15 | 2024-01-30 | 基因泰克公司 | 组合疗法中的egfr抑制剂和perk活化剂及其用于治疗癌症的用途 |
| CN115707704B (zh) * | 2021-08-20 | 2024-09-13 | 广东医诺维申生物技术有限公司 | 氘代稠合三环类化合物及其组合物和用途 |
| JP2025538804A (ja) | 2022-12-08 | 2025-11-28 | アッシア ケミカル インダストリーズ リミテッド | ジパレルチニブの固体状態の形態及びそれを調製するための方法 |
| CN115785107B (zh) * | 2022-12-15 | 2024-11-12 | 南京雷正医药科技有限公司 | 一种取代8,9-二氢嘧啶并[5,4-b]吲嗪类化合物、药物组合物及其用途 |
| CN121285557A (zh) * | 2023-05-31 | 2026-01-06 | 大鹏药品工业株式会社 | 喹啉取代化合物的晶体 |
| WO2025141465A1 (en) | 2023-12-27 | 2025-07-03 | Assia Chemical Industries Ltd. | Solid state forms of zipalertinib hydrochloride and process for preparation thereof |
| WO2025167588A1 (zh) * | 2024-02-05 | 2025-08-14 | 苏州科睿思制药有限公司 | Zipalertinib的晶型及其制备方法和用途 |
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| TW440562B (en) * | 1994-05-20 | 2001-06-16 | Taiho Pharmaceutical Co Ltd | Condensed-indan derivative and pharmaceutically acceptable salts thereof |
| PT2452940E (pt) * | 2009-07-10 | 2015-02-27 | Taiho Pharmaceutical Co Ltd | Composto azabiciclo e seu sal |
| TW201309668A (zh) | 2011-01-07 | 2013-03-01 | Taiho Pharmaceutical Co Ltd | 新穎雙環式化合物或其鹽 |
| WO2013047813A1 (ja) | 2011-09-30 | 2013-04-04 | 大鵬薬品工業株式会社 | １，２，４－トリアジン－６－カルボキサミド誘導体 |
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2014
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- 2014-08-22 ES ES14837210.5T patent/ES2656712T3/es active Active
- 2014-08-22 CN CN201480058192.XA patent/CN105683195B/zh active Active
- 2014-08-22 KR KR1020167007071A patent/KR101906688B1/ko active Active
- 2014-08-22 NO NO14837210A patent/NO3037424T3/no unknown
- 2014-08-22 SG SG11201600759XA patent/SG11201600759XA/en unknown
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- 2014-08-22 DK DK14837210.5T patent/DK3037424T3/en active
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2016
- 2016-02-02 PH PH12016500225A patent/PH12016500225A1/en unknown
- 2016-12-19 US US15/382,883 patent/US9758526B2/en active Active
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| WO2011046964A2 (en) * | 2009-10-12 | 2011-04-21 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
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