CA2932435C - (6s,9as)-n-benzyl-8-((6-(3-(4-ethylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-6-((2-fluoro-4-hydroxyphenyl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1h-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide and pharmaceutically acceptable salts thereof - Google Patents
(6s,9as)-n-benzyl-8-((6-(3-(4-ethylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-6-((2-fluoro-4-hydroxyphenyl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1h-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide and pharmaceutically acceptable salts thereof Download PDFInfo
- Publication number
- CA2932435C CA2932435C CA2932435A CA2932435A CA2932435C CA 2932435 C CA2932435 C CA 2932435C CA 2932435 A CA2932435 A CA 2932435A CA 2932435 A CA2932435 A CA 2932435A CA 2932435 C CA2932435 C CA 2932435C
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- Prior art keywords
- compound
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- mmol
- azetidin
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- 150000003839 salts Chemical class 0.000 title claims abstract description 66
- ZGNKNLOBYFTGRG-GIWKVKTRSA-N (6S,9aS)-N-benzyl-8-[[6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl]methyl]-6-[(2-fluoro-4-hydroxyphenyl)methyl]-4,7-dioxo-2-prop-2-enyl-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C1CN(CC)CCN1C1CN(C=2N=C(CN3C([C@H](CC=4C(=CC(O)=CC=4)F)N4[C@@H](N(N(CC=C)CC4=O)C(=O)NCC=4C=CC=CC=4)C3)=O)C=CC=2)C1 ZGNKNLOBYFTGRG-GIWKVKTRSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 458
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 25
- 125000005843 halogen group Chemical group 0.000 abstract description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 description 378
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 231
- 239000002904 solvent Substances 0.000 description 154
- 238000000034 method Methods 0.000 description 137
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 238000006243 chemical reaction Methods 0.000 description 88
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 78
- -1 [1,2,4]triazine-l-carboxamide compound Chemical class 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000047 product Substances 0.000 description 65
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- 101150041968 CDC13 gene Proteins 0.000 description 59
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 59
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 46
- 239000011259 mixed solution Substances 0.000 description 46
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 43
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- 239000012044 organic layer Substances 0.000 description 41
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- 125000006239 protecting group Chemical group 0.000 description 36
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- 238000012360 testing method Methods 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
- 238000000746 purification Methods 0.000 description 28
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 19
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 18
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
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- 210000004027 cell Anatomy 0.000 description 15
- 238000010511 deprotection reaction Methods 0.000 description 15
- 239000012046 mixed solvent Substances 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 13
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 13
- MHZGAVWIXHVIET-UHFFFAOYSA-N N1(NC=NC=C1)C(=O)N Chemical compound N1(NC=NC=C1)C(=O)N MHZGAVWIXHVIET-UHFFFAOYSA-N 0.000 description 13
- 229960002448 dasatinib Drugs 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 239000012085 test solution Substances 0.000 description 12
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 11
- 229910052736 halogen Inorganic materials 0.000 description 11
- 150000002367 halogens Chemical class 0.000 description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
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- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 8
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Classifications
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- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2013267687 | 2013-12-25 | ||
| JP2013-267687 | 2013-12-25 | ||
| PCT/JP2014/083932 WO2015098853A1 (ja) | 2013-12-25 | 2014-12-22 | （６Ｓ，９ａＳ）－Ｎ－ベンジル－６－［（４－ヒドロキシフェニル）メチル］－４，７－ジオキソ－８－（｛６－［３－（ピペラジン－１－イル）アゼチジン－１－イル］ピリジン－２－イル｝メチル）－２－（プロプ－２－エン－１－イル）－オクタヒドロ－１Ｈ－ピラジノ［２，１－ｃ］［１，２，４］トリアジン－１－カルボキサミド化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2932435A1 CA2932435A1 (en) | 2015-07-02 |
| CA2932435C true CA2932435C (en) | 2021-08-17 |
Family
ID=53399298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2932435A Active CA2932435C (en) | 2013-12-25 | 2014-12-22 | (6s,9as)-n-benzyl-8-((6-(3-(4-ethylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-6-((2-fluoro-4-hydroxyphenyl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1h-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide and pharmaceutically acceptable salts thereof |
Country Status (34)
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| EP (1) | EP3088401B1 (https=) |
| JP (1) | JP6085040B2 (https=) |
| KR (1) | KR102307053B1 (https=) |
| CN (1) | CN105873932B (https=) |
| AR (1) | AR098908A1 (https=) |
| AU (1) | AU2014371148B2 (https=) |
| BR (1) | BR112016013572B1 (https=) |
| CA (1) | CA2932435C (https=) |
| CL (1) | CL2016001419A1 (https=) |
| CY (1) | CY1122521T1 (https=) |
| DK (1) | DK3088401T3 (https=) |
| ES (1) | ES2728353T3 (https=) |
| HR (1) | HRP20190908T1 (https=) |
| HU (1) | HUE044541T2 (https=) |
| IL (1) | IL245961A0 (https=) |
| JO (1) | JO3809B1 (https=) |
| LT (1) | LT3088401T (https=) |
| ME (1) | ME03391B (https=) |
| MX (1) | MX365376B (https=) |
| MY (1) | MY173946A (https=) |
| PE (1) | PE20160932A1 (https=) |
| PH (1) | PH12016501079A1 (https=) |
| PL (1) | PL3088401T3 (https=) |
| PT (1) | PT3088401T (https=) |
| RS (1) | RS58955B1 (https=) |
| RU (1) | RU2669805C2 (https=) |
| SG (1) | SG11201604496YA (https=) |
| SI (1) | SI3088401T1 (https=) |
| SM (1) | SMT201900306T1 (https=) |
| TR (1) | TR201908392T4 (https=) |
| TW (1) | TWI681961B (https=) |
| UA (1) | UA116923C2 (https=) |
| WO (1) | WO2015098853A1 (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2468281T3 (en) | 2009-08-19 | 2016-03-21 | Eisai R&D Man Co Ltd | Quinolinderivatholdig pharmaceutical composition |
| JP6038128B2 (ja) | 2011-06-03 | 2016-12-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー |
| PT3524595T (pt) | 2014-08-28 | 2022-09-19 | Eisai R&D Man Co Ltd | Derivado de quinolina altamente puro e método para produção do mesmo |
| AU2016224583B2 (en) | 2015-02-25 | 2021-06-03 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| BR112017027227B1 (pt) * | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| CA2986999C (en) * | 2015-06-23 | 2023-08-08 | Eisai R&D Management Co., Ltd. | Crystal of (6s,9as)-n-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2h-pyrazino[2,1-c][1,2,4]triazine-1(6h)-carboxamide |
| JP6553726B2 (ja) | 2015-08-20 | 2019-07-31 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| CN108084067B (zh) * | 2016-11-22 | 2019-08-30 | 重庆圣华曦药业股份有限公司 | 一种立他司特中间体的制备方法 |
| JP6581320B2 (ja) | 2017-02-08 | 2019-09-25 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療用医薬組成物 |
| EP3624800A4 (en) | 2017-05-16 | 2021-02-17 | Eisai R&D Management Co., Ltd. | TREATMENT OF HEPATOCELLULAR CARCINOMA |
| MX2022005056A (es) | 2019-10-29 | 2022-05-18 | Eisai R&D Man Co Ltd | Combinacion de un antagonista de pd-1, un inhibidor tirosina cinasa de vegfr/fgfr/ret y un inhibidor de cbp/beta-catenina para el tratamiento del cancer. |
| AR121544A1 (es) | 2020-03-12 | 2022-06-15 | 3 2 Pharma | Inhibidores de la vía de señalización por cbp / catenina y sus usos |
| WO2021183791A1 (en) | 2020-03-12 | 2021-09-16 | City Of Hope | Wnt/cbp/catenin signaling pathway inhibitors and uses thereof |
| US20230390296A1 (en) | 2020-10-30 | 2023-12-07 | Keio University | Novel treatment and prevention of sarcopenia-related diseases |
| US20240352020A1 (en) * | 2021-08-26 | 2024-10-24 | 3+2 Pharma, Llc | Pyrazole-containing cbp/catenin antagonists and uses thereof |
| MX2024002060A (es) * | 2021-09-08 | 2024-03-01 | Eisai R&D Man Co Ltd | Composicion farmaceutica para tratar tumores solidos. |
| CN116262120A (zh) * | 2021-12-13 | 2023-06-16 | 上海中医药大学 | 特异性结合TRAF2的试剂在制备Wnt通路抑制剂中的应用 |
| WO2023140369A1 (en) * | 2022-01-18 | 2023-07-27 | Prism BioLab Co., Ltd. | Phosphoric acid derivatives |
| US20250177406A1 (en) | 2022-03-31 | 2025-06-05 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating tumors |
| CN115784934A (zh) * | 2022-11-22 | 2023-03-14 | 上海吉奉生物科技有限公司 | 一种酪氨酸衍生物的合成方法 |
| JPWO2024209717A1 (https=) | 2023-04-06 | 2024-10-10 | ||
| WO2025174646A1 (en) * | 2024-02-12 | 2025-08-21 | Albert Einstein College Of Medicine | Inhibitors of beta-catenin c-terminal domain and methods of use |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1444235B1 (en) * | 2001-10-12 | 2008-06-11 | Choongwae Pharma Corporation | Reverse-turn mimetics and method relating thereto |
| US8080657B2 (en) | 2001-10-12 | 2011-12-20 | Choongwae Pharma Corporation | Compounds of reverse turn mimetics and the use thereof |
| US7671054B1 (en) * | 2001-10-12 | 2010-03-02 | Choongwae Pharma Corporation | Reverse-turn mimetics and method relating thereto |
| JP2009184924A (ja) | 2006-05-31 | 2009-08-20 | Eisai R & D Management Co Ltd | 生物学的試薬用化合物 |
| WO2009148192A1 (en) | 2008-06-06 | 2009-12-10 | Prism Biolab Corporation | Alpha helix mimetics and methods relating thereto |
| CN102459271B (zh) * | 2009-04-15 | 2014-07-02 | Jw制药公司 | 回折模拟物的新化合物及其制备方法和用途 |
| CN103209982B (zh) * | 2010-10-14 | 2016-03-16 | Jw制药公司 | 反转模拟物的化合物、其制造方法及其用途 |
| US20140051706A1 (en) * | 2011-02-25 | 2014-02-20 | Prism Pharma Co., Ltd. | Alpha helix mimetics and methods relating thereto |
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2014
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- 2014-12-22 WO PCT/JP2014/083932 patent/WO2015098853A1/ja not_active Ceased
- 2014-12-22 RU RU2016122867A patent/RU2669805C2/ru active
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- 2014-12-22 UA UAA201606261A patent/UA116923C2/uk unknown
- 2014-12-22 HR HRP20190908TT patent/HRP20190908T1/hr unknown
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- 2014-12-22 PT PT14873998T patent/PT3088401T/pt unknown
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- 2014-12-22 JP JP2015554886A patent/JP6085040B2/ja active Active
- 2014-12-22 TR TR2019/08392T patent/TR201908392T4/tr unknown
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