JP6523303B2 - Ｓｈｐ２の活性を阻害するための１−ピリダジン／トリアジン−３−イル−ピペラジン／ピペリジン／ピロリジン誘導体およびその組成物 - Google Patents
Ｓｈｐ２の活性を阻害するための１−ピリダジン／トリアジン−３−イル−ピペラジン／ピペリジン／ピロリジン誘導体およびその組成物 Download PDFInfo
- Publication number
- JP6523303B2 JP6523303B2 JP2016547026A JP2016547026A JP6523303B2 JP 6523303 B2 JP6523303 B2 JP 6523303B2 JP 2016547026 A JP2016547026 A JP 2016547026A JP 2016547026 A JP2016547026 A JP 2016547026A JP 6523303 B2 JP6523303 B2 JP 6523303B2
- Authority
- JP
- Japan
- Prior art keywords
- amino
- alkyl
- substituted
- hydrogen
- hydroxy
- 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.)
- Active
Links
Classifications
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
-
- 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
- C07D403/02—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 two hetero rings
- C07D403/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461928738P | 2014-01-17 | 2014-01-17 | |
| US61/928,738 | 2014-01-17 | ||
| PCT/IB2015/050343 WO2015107493A1 (en) | 2014-01-17 | 2015-01-16 | 1 -pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017503000A JP2017503000A (ja) | 2017-01-26 |
| JP2017503000A5 JP2017503000A5 (enExample) | 2018-02-22 |
| JP6523303B2 true JP6523303B2 (ja) | 2019-05-29 |
Family
ID=52462361
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016547026A Active JP6523303B2 (ja) | 2014-01-17 | 2015-01-16 | Ｓｈｐ２の活性を阻害するための１−ピリダジン／トリアジン−３−イル−ピペラジン／ピペリジン／ピロリジン誘導体およびその組成物 |
Country Status (6)
| Country | Link |
|---|---|
| US (4) | US10093646B2 (enExample) |
| EP (1) | EP3094627B1 (enExample) |
| JP (1) | JP6523303B2 (enExample) |
| CN (1) | CN105899491B (enExample) |
| ES (1) | ES2699351T3 (enExample) |
| WO (1) | WO2015107493A1 (enExample) |
Families Citing this family (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| WO2015092819A2 (en) | 2013-12-21 | 2015-06-25 | Nektar Therapeutics (India) Pvt. Ltd. | Derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5- amine |
| ES2699354T3 (es) | 2014-01-17 | 2019-02-08 | Novartis Ag | Derivados de 1-(triazin-3-il/piridazin-3-il)-piper(-azin)idina y composiciones de las mismas para inhibir la actividad de SHP2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| JP6878316B2 (ja) | 2015-06-19 | 2021-05-26 | ノバルティス アーゲー | Ｓｈｐ２の活性を阻害するための化合物および組成物 |
| CN112625028B (zh) | 2015-06-19 | 2024-10-29 | 诺华股份有限公司 | 用于抑制shp2活性的化合物和组合物 |
| WO2016203404A1 (en) * | 2015-06-19 | 2016-12-22 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
| SI3371152T1 (sl) * | 2015-11-05 | 2021-06-30 | Celgene Quanticel Research, Inc. | Sestavki, ki vsebujejo lisin specifični demetilaze-1 inhibitor s piridinskim obročem in njihova uporaba pri zdravljenju raka |
| CN107286150B (zh) * | 2016-04-11 | 2020-07-07 | 中国科学院上海有机化学研究所 | N-杂环类化合物、其中间体、制备方法、药物组合物和应用 |
| WO2017210134A1 (en) * | 2016-05-31 | 2017-12-07 | Board Of Regents, University Of Texas System | Heterocyclic inhibitors of ptpn11 |
| CN109311848B (zh) * | 2016-06-07 | 2022-02-01 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| RU2744988C2 (ru) | 2016-06-14 | 2021-03-17 | Новартис Аг | Соединения и композиции для подавления активности shp2 |
| AU2017296289A1 (en) * | 2016-07-12 | 2019-01-31 | Revolution Medicines, Inc. | 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric SHP2 inhibitors |
| EP3515916B1 (en) | 2016-09-22 | 2023-06-07 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| TWI848901B (zh) | 2016-10-24 | 2024-07-21 | 美商傳達治療有限公司 | Shp2磷酸酶抑制劑及其使用方法 |
| CA3048340A1 (en) | 2017-01-10 | 2018-07-19 | Novartis Ag | Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor |
| JP7240319B2 (ja) | 2017-01-23 | 2023-03-15 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての二環式化合物 |
| CN110431134A (zh) * | 2017-01-23 | 2019-11-08 | 锐新医药公司 | 作为变构shp2抑制剂的吡啶化合物 |
| SMT202400385T1 (it) | 2017-03-23 | 2024-11-15 | Jacobio Pharmaceuticals Co Ltd | Nuovi derivati eterociclici utili come inibitori di shp2 |
| EP3630770B1 (en) | 2017-05-26 | 2024-08-28 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| KR20200051684A (ko) | 2017-09-07 | 2020-05-13 | 레볼루션 메디슨즈, 인크. | 암 치료를 위한 shp2 억제제 조성물 및 방법 |
| US10435389B2 (en) | 2017-09-11 | 2019-10-08 | Krouzon Pharmaccuticals, Inc. | Octahydrocyclopenta[c]pyrrole allosteric inhibitors of SHP2 |
| EP3687997A1 (en) | 2017-09-29 | 2020-08-05 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| EP3694848A1 (en) * | 2017-10-12 | 2020-08-19 | Revolution Medicines, Inc. | Pyridine, pyrazine, and triazine compounds as allosteric shp2 inhibitors |
| TW201927791A (zh) | 2017-12-15 | 2019-07-16 | 美商銳新醫藥公司 | 作為變構shp2抑制劑的多環化合物 |
| CN108113984B (zh) * | 2017-12-20 | 2021-05-07 | 中国科学院成都生物研究所 | Shp2抑制剂在制备抗肿瘤的药物中的用途 |
| CN115448923B (zh) * | 2018-02-13 | 2024-03-22 | 上海青煜医药科技有限公司 | 嘧啶并环化合物及其制备方法和应用 |
| CN110655520A (zh) * | 2018-06-29 | 2020-01-07 | 上海青煜医药科技有限公司 | 嘧啶并环化合物及其制备方法和应用 |
| JP7335882B2 (ja) * | 2018-02-13 | 2023-08-30 | ブルーレイ セラピューティクス （シャンハイ） カンパニー，リミティド | ピリミジン縮合環式化合物及びその製造方法、並びに使用 |
| MX2020008754A (es) | 2018-03-02 | 2020-12-07 | Otsuka Pharma Co Ltd | Compuestos farmaceuticos. |
| IL277071B2 (en) | 2018-03-08 | 2024-07-01 | Incyte Corp | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| WO2019183364A1 (en) | 2018-03-21 | 2019-09-26 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine shp2 phosphatase inhibitors and methods of use thereof |
| AU2019239658A1 (en) | 2018-03-21 | 2020-11-12 | Suzhou Puhe BioPharma Co., Ltd. | SHP2 inhibitors and uses thereof |
| US20220315586A1 (en) | 2018-03-21 | 2022-10-06 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| KR20200143417A (ko) | 2018-04-10 | 2020-12-23 | 레볼루션 메디슨즈, 인크. | Shp2 억제제 조성물, 암을 치료하는 방법 및 shp2 돌연변이를 갖는 대상체를 확인하는 방법 |
| US20190336609A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C40-, C28-, and C-32-Linked Rapamycin Analogs as mTOR Inhibitors |
| US10954243B2 (en) | 2018-05-02 | 2021-03-23 | Navire Pharma, Inc. | Substituted heterocyclic inhibitors of PTPN11 |
| CN115721648A (zh) * | 2018-05-09 | 2023-03-03 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| MX2021000795A (es) | 2018-07-24 | 2021-04-12 | Taiho Pharmaceutical Co Ltd | Compuestos heterociclicos para inhibir la actividad de shp2. |
| EP3833670B1 (en) | 2018-08-10 | 2024-04-17 | Navire Pharma, Inc. | 6-(4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4(3h)-one derivatives and related compounds as ptpn11 (shp2) inhibitors for treating cancer |
| WO2020061103A1 (en) | 2018-09-18 | 2020-03-26 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
| US20210393623A1 (en) | 2018-09-26 | 2021-12-23 | Jacobio Pharmaceuticals Co., Ltd. | Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors |
| MX2021003459A (es) | 2018-09-29 | 2021-06-18 | Novartis Ag | Proceso de fabricacion de un compuesto para la inhibicion de la actividad de shp2. |
| WO2020065452A1 (en) | 2018-09-29 | 2020-04-02 | Novartis Ag | Manufacture of compounds and compositions for inhibiting the activity of shp2 |
| EP3860717A1 (en) | 2018-10-03 | 2021-08-11 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| WO2020076723A1 (en) | 2018-10-08 | 2020-04-16 | Revolution Medicines, Inc. | Shp2 inhibitor compositions for use in treating cancer |
| EP3867238B1 (en) | 2018-10-17 | 2023-06-07 | Array BioPharma Inc. | Protein tyrosine phosphatase inhibitors |
| CN111138412B (zh) * | 2018-11-06 | 2023-09-15 | 上海奕拓医药科技有限责任公司 | 一种螺芳环化合物及其应用 |
| JP2022506887A (ja) * | 2018-11-07 | 2022-01-17 | シャンハイ リンジーン バイオファーマ カンパニー リミテッド | 窒素含有縮合複素環系ｓｈｐ２阻害剤化合物、製造方法及び使用 |
| CN111153899B (zh) * | 2018-11-08 | 2023-12-01 | 四川科伦博泰生物医药股份有限公司 | 一种取代吡啶化合物、其制备方法和用途 |
| WO2020118066A1 (en) | 2018-12-05 | 2020-06-11 | Mirati Therapeutics, Inc. | Combination therapies |
| CN111484491B (zh) * | 2019-01-25 | 2022-09-02 | 四川科伦博泰生物医药股份有限公司 | 取代吡啶并环化合物、其制备方法和用途 |
| CN113382774A (zh) | 2019-02-12 | 2021-09-10 | 诺华股份有限公司 | 包含tno155和krasg12c抑制剂的药物组合 |
| US20230148450A9 (en) | 2019-03-01 | 2023-05-11 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| US20230096028A1 (en) | 2019-03-01 | 2023-03-30 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| US11033547B2 (en) | 2019-03-07 | 2021-06-15 | Merck Patent Gmbh | Carboxamide-pyrimidine derivatives as SHP2 antagonists |
| PH12021552227A1 (en) * | 2019-04-02 | 2022-05-30 | Array Biopharma Inc | Protein tyrosine phosphatase inhibitors |
| AU2020271838A1 (en) | 2019-04-08 | 2021-08-19 | Merck Patent Gmbh | Pyrimidinone derivatives as SHP2 antagonists |
| TW202112785A (zh) * | 2019-06-07 | 2021-04-01 | 美商銳新醫藥公司 | Ｓｈｐ２抑制劑的固體形式 |
| TWI817018B (zh) | 2019-06-28 | 2023-10-01 | 美商艾瑞生藥股份有限公司 | 用於治療ｂｒａｆ相關的疾病和失調症之化合物 |
| CN112300160A (zh) * | 2019-08-01 | 2021-02-02 | 上海奕拓医药科技有限责任公司 | 一种螺芳环化合物、其制备及应用 |
| EP3772513A1 (en) | 2019-08-09 | 2021-02-10 | C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro Screening | Shp2 inhibitors |
| GB201911928D0 (en) | 2019-08-20 | 2019-10-02 | Otsuka Pharma Co Ltd | Pharmaceutical compounds |
| CN114127053B (zh) * | 2019-09-06 | 2023-06-13 | 四川科伦博泰生物医药股份有限公司 | 一种取代吡嗪化合物、其制备方法和用途 |
| CA3154862A1 (en) | 2019-09-24 | 2021-04-01 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of making and using the same |
| CN112724145A (zh) * | 2019-10-14 | 2021-04-30 | 杭州雷索药业有限公司 | 用于抑制shp2活性的吡嗪衍生物 |
| CN115894606A (zh) | 2019-11-04 | 2023-04-04 | 锐新医药公司 | Ras抑制剂 |
| WO2021091967A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| CA3160142A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| KR20220100903A (ko) | 2019-11-08 | 2022-07-18 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로아릴 화합물 및 이의 용도 |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| MX2022008305A (es) | 2020-01-07 | 2022-08-08 | Revolution Medicines Inc | Dosificacion de inhibidores de shp2 y metodos de tratamiento del cancer. |
| WO2021143823A1 (zh) * | 2020-01-16 | 2021-07-22 | 浙江海正药业股份有限公司 | 吡啶或嘧啶类衍生物及其制备方法和用途 |
| US20230348467A1 (en) | 2020-01-16 | 2023-11-02 | Zhejiang Hisun Pharmaceutical Co., Ltd. | Heteroaryl Derivative, Preparation Method Therefor, And Use Thereof |
| KR20220148847A (ko) | 2020-02-28 | 2022-11-07 | 노파르티스 아게 | 다브라페닙, erk 억제제, 및 shp2 억제제를 포함하는 삼중 약학적 조합물 |
| WO2021247836A1 (en) | 2020-06-03 | 2021-12-09 | Board Of Regents, The University Of Texas System | Methods for targeting shp-2 to overcome resistance |
| CN113754683A (zh) | 2020-06-05 | 2021-12-07 | 上海奕拓医药科技有限责任公司 | 同位素取代的螺芳环化合物及其应用 |
| JP2023530351A (ja) | 2020-06-18 | 2023-07-14 | レヴォリューション・メディスンズ，インコーポレイテッド | Ｒａｓ阻害剤への獲得耐性を遅延させる、防止する、及び、治療する方法 |
| WO2021259077A1 (zh) * | 2020-06-22 | 2021-12-30 | 四川科伦博泰生物医药股份有限公司 | 取代吡嗪类化合物，包含其的药物组合物及其用途 |
| CN115916786B (zh) | 2020-07-08 | 2025-10-17 | 诺华股份有限公司 | 用于抑制shp2活性的化合物和组合物的制造 |
| KR20230081726A (ko) | 2020-09-03 | 2023-06-07 | 레볼루션 메디슨즈, 인크. | Shp2 돌연변이가 있는 악성 종양을 치료하기 위한 sos1 억제제의 용도 |
| KR20230067635A (ko) | 2020-09-15 | 2023-05-16 | 레볼루션 메디슨즈, 인크. | 암의 치료에서 ras 억제제로서 인돌 유도체 |
| WO2022140427A1 (en) | 2020-12-22 | 2022-06-30 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
| EP4039685A1 (en) | 2021-02-08 | 2022-08-10 | Irbm S.P.A. | Azabicyclic shp2 inhibitors |
| TWI825637B (zh) | 2021-03-31 | 2023-12-11 | 美商輝瑞股份有限公司 | 啶－１，６（２ｈ，７ｈ）－二酮 |
| EP4067358A1 (en) | 2021-04-02 | 2022-10-05 | C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro Screening | (s)-1-(5-((pyridin-3-yl)thio)pyrazin-2-yl)-4'h,6'h-spiro[piperidine-4,5'-pyrrolo[1,2-b]pyrazol]-4'-amine derivatives and similar compounds as shp2 inhibitors for the treatment of e.g. cancer |
| CA3217393A1 (en) | 2021-05-05 | 2022-11-10 | Elena S. Koltun | Ras inhibitors |
| CN118852330A (zh) | 2021-05-05 | 2024-10-29 | 锐新医药公司 | 用于治疗癌症的ras抑制剂 |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| MX2023014563A (es) | 2021-06-09 | 2024-02-08 | Hoffmann La Roche | Combinacion de un inhibidor de braf particular (interruptor de paradoja) y un antagonista de union al eje de pd-1 para su uso en el tratamiento de cancer. |
| TW202313046A (zh) | 2021-06-09 | 2023-04-01 | 瑞士商赫孚孟拉羅股份公司 | 用於癌症治療之組合療法 |
| WO2022259157A1 (en) | 2021-06-09 | 2022-12-15 | Novartis Ag | A triple pharmaceutical combination comprising dabrafenib, trametinib and a shp2 inhibitor |
| TW202317100A (zh) | 2021-06-23 | 2023-05-01 | 瑞士商諾華公司 | 包含ｋｒａｓ ｇ１２ｃ抑制劑的藥物組合及其用於治療癌症之用途 |
| EP4395769A1 (en) | 2021-09-01 | 2024-07-10 | Novartis AG | Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| AU2022383040A1 (en) | 2021-11-04 | 2024-03-07 | F. Hoffmann-La Roche Ag | Novel use of quinazolinone compound for the treatment of cancer |
| JP2025510572A (ja) | 2022-03-08 | 2025-04-15 | レボリューション メディシンズ インコーポレイテッド | 免疫不応性肺癌を治療するための方法 |
| CN116903581A (zh) * | 2022-04-14 | 2023-10-20 | 山东大学 | Shp2/hdac双靶点抑制剂及其制备方法和应用 |
| CN115611869B (zh) * | 2022-05-11 | 2024-08-09 | 山东大学 | 杂环吡嗪衍生物与其在制备shp2抑制剂中的应用 |
| AU2023285116A1 (en) | 2022-06-10 | 2024-12-19 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| EP4345101A1 (en) | 2022-09-29 | 2024-04-03 | Irbm S.P.A. | Azole derivatives as shp2 inhibitors |
| CN115677828B (zh) * | 2022-11-02 | 2024-10-18 | 四川大学 | 一种抗肿瘤的间二氯苯酚衍生物及其制备方法 |
| CN120359214A (zh) | 2022-12-15 | 2025-07-22 | 豪夫迈·罗氏有限公司 | 用于癌症治疗的组合疗法 |
| CN116332908B (zh) * | 2023-03-21 | 2024-07-02 | 杭州医学院 | 一种shp2变构抑制剂及其制备方法和应用 |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| TW202446388A (zh) | 2023-04-14 | 2024-12-01 | 美商銳新醫藥公司 | Ｒａｓ抑制劑之結晶形式、含有其之組合物及其使用方法 |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| WO2024218632A1 (en) | 2023-04-17 | 2024-10-24 | Array Biopharma Inc. | Erk protein kinase inhibitors |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025034919A1 (en) | 2023-08-08 | 2025-02-13 | Quanta Therapeutics, Inc. | Combination therapies with kras modulators |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025106901A1 (en) | 2023-11-17 | 2025-05-22 | Quanta Therapeutics, Inc. | Combination cancer therapies with a kras modulator and an rtk-mapk pathway inhibitor |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH445129A (fr) | 1964-04-29 | 1967-10-15 | Nestle Sa | Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé |
| US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
| US3453257A (en) | 1967-02-13 | 1969-07-01 | Corn Products Co | Cyclodextrin with cationic properties |
| US3426011A (en) | 1967-02-13 | 1969-02-04 | Corn Products Co | Cyclodextrins with anionic properties |
| US3453259A (en) | 1967-03-22 | 1969-07-01 | Corn Products Co | Cyclodextrin polyol ethers and their oxidation products |
| JPS6041077B2 (ja) | 1976-09-06 | 1985-09-13 | 喜徳 喜谷 | １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体 |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4261989A (en) | 1979-02-19 | 1981-04-14 | Kaken Chemical Co. Ltd. | Geldanamycin derivatives and antitumor drug |
| FR2567518B1 (fr) | 1984-07-11 | 1987-11-13 | Sanofi Sa | Nouveaux composes a noyau heterocyclique azote, leur preparation et les medicaments qui en contiennent |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| US4959368A (en) | 1986-02-24 | 1990-09-25 | Mitsui Petrochemical Industries Ltd. | Therapeutic agent for neurological diseases |
| US5266573A (en) | 1989-08-07 | 1993-11-30 | Elf Sanofi | Trifluoromethylphenyltetrahydropyridines for the treatment and/or prophylaxis of intestinal motility disorders |
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| DK169008B1 (da) | 1990-06-01 | 1994-07-25 | Holec Lk A S | Fremgangsmåde og skærm til afskærmning af en strømtransformer samt strømtransformer med en sådan afskærmning |
| GB9012316D0 (en) * | 1990-06-01 | 1990-07-18 | Wellcome Found | Pharmacologically active cns compounds |
| EP0647450A1 (en) | 1993-09-09 | 1995-04-12 | BEHRINGWERKE Aktiengesellschaft | Improved prodrugs for enzyme mediated activation |
| IL115849A0 (en) | 1994-11-03 | 1996-01-31 | Merz & Co Gmbh & Co | Tangential filtration preparation of liposomal drugs and liposome product thereof |
| CA2369945A1 (en) | 1999-04-06 | 2000-10-12 | James L. Kelley | Neurotrophic thio substituted pyrimidines |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| JP4272338B2 (ja) | 2000-09-22 | 2009-06-03 | バイエル アクチェンゲゼルシャフト | ピリジン誘導体 |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| EP2090571B1 (de) | 2001-10-17 | 2012-05-16 | Boehringer Ingelheim Pharma GmbH & Co. KG | Pyrimidinderivate, Arzneimittel enthaltend diese Verbindungen, deren Verwendung und Verfahren zu ihrer Herstellung |
| ES2485841T3 (es) | 2002-02-01 | 2014-08-14 | Ariad Pharmaceuticals, Inc | Compuestos que contienen fósforo y usos de los mismos |
| HRP20040800B1 (en) | 2002-03-05 | 2012-11-30 | Merck Frosst Canada & Co Axys | Cathepsin cysteine protease inhibitors |
| TWI275390B (en) | 2002-04-30 | 2007-03-11 | Wyeth Corp | Process for the preparation of 7-substituted-3- quinolinecarbonitriles |
| GB0300783D0 (en) * | 2003-01-14 | 2003-02-12 | Btg Int Ltd | Treatment of neurodegenerative conditions |
| US7399865B2 (en) | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
| JP4978192B2 (ja) | 2004-04-01 | 2012-07-18 | アステラス製薬株式会社 | ピラジン誘導体およびその医薬的使用 |
| AU2005249380C1 (en) * | 2004-04-23 | 2012-09-20 | Exelixis, Inc. | Kinase modulators and methods of use |
| KR20150002863A (ko) | 2004-09-02 | 2015-01-07 | 제넨테크, 인크. | 헤지호그 신호전달에 대한 피리딜 억제제 |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| AU2006290715A1 (en) | 2005-09-13 | 2007-03-22 | Palau Pharma, S.A. | 2-aminopyrimidine derivatives as modulators of the histamine H4 receptor activity |
| US7515405B2 (en) | 2006-07-25 | 2009-04-07 | Hewlett-Packard Development Company, L.P. | Anti-rotation mechanism for an electronic device |
| US20090137549A1 (en) | 2006-11-09 | 2009-05-28 | Paul John Edward | Novel compounds useful for the treatment of degenerative & inflamatory diseases |
| JP2010518083A (ja) | 2007-02-12 | 2010-05-27 | メルク・シャープ・エンド・ドーム・コーポレイション | ピペリジン誘導体 |
| DK2137162T3 (en) * | 2007-03-15 | 2018-11-26 | Novartis Ag | Organic compounds and their applications |
| EP2205242B1 (en) | 2007-09-12 | 2015-04-15 | Genentech, Inc. | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use |
| JP5348725B2 (ja) | 2007-10-25 | 2013-11-20 | ジェネンテック， インコーポレイテッド | チエノピリミジン化合物の製造方法 |
| WO2009131687A2 (en) | 2008-04-22 | 2009-10-29 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| EP2310381A1 (en) | 2008-06-13 | 2011-04-20 | Novartis AG | 2,4'-bipyridinyl compounds as protein kinase d inhibitors useful for the treatment of ia heart failure and cancer |
| BRPI0914891A2 (pt) | 2008-06-20 | 2015-11-24 | Metabolex Inc | agonistas de aril gpr119 e usos dos mesmos |
| US8168784B2 (en) | 2008-06-20 | 2012-05-01 | Abbott Laboratories | Processes to make apoptosis promoters |
| NZ624345A (en) | 2008-06-27 | 2016-07-29 | Celgene Avilomics Res Inc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| US20110306606A1 (en) | 2008-12-10 | 2011-12-15 | Jei Man Ryu | Novel 2,6-substituted-3-nitropyridine derivative, method for preparing same, and pharmaceutical composition including same |
| FR2941696B1 (fr) | 2009-02-05 | 2011-04-15 | Sanofi Aventis | Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| US9567318B2 (en) | 2009-08-17 | 2017-02-14 | Memorial Sloan-Kettering Cancer Center | Substituted pyrimidine compounds and uses thereof |
| WO2011078143A1 (ja) | 2009-12-22 | 2011-06-30 | 塩野義製薬株式会社 | ピリミジン誘導体およびそれらを含有する医薬組成物 |
| MY177250A (en) | 2010-06-30 | 2020-09-10 | Fujifilm Corp | Novel nicotinamide derivative or salt thereof |
| WO2012009217A1 (en) | 2010-07-13 | 2012-01-19 | Merck Sharp & Dohme Corp. | Spirocyclic compounds |
| CA2806341C (en) | 2010-07-29 | 2020-03-24 | Rigel Pharmaceuticals, Inc. | Ampk-activating heterocyclic compounds and methods for using the same |
| WO2012027495A1 (en) * | 2010-08-27 | 2012-03-01 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| WO2012052948A1 (en) | 2010-10-20 | 2012-04-26 | Pfizer Inc. | Pyridine- 2- derivatives as smoothened receptor modulators |
| JP5727276B2 (ja) | 2011-03-04 | 2015-06-03 | 協同油脂株式会社 | グリース組成物及びグリース封入転がり軸受 |
| JP6082011B2 (ja) | 2011-09-12 | 2017-02-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | キナーゼ活性のモジュレーターとして使用するためのアミノピリミジン誘導体 |
| WO2013096093A1 (en) | 2011-12-21 | 2013-06-27 | Merck Sharp & Dohme Corp. | Compounds as dgat-1 inhibitors |
| CA2874546A1 (en) | 2012-06-07 | 2013-12-12 | F. Hoffmann-La Roche Ag | Pyrazolopyrimidone and pyrazolopyridone inhibitors of tankyrase |
| EP2903985A1 (en) | 2012-10-03 | 2015-08-12 | Advinus Therapeutics Limited | Spirocyclic compounds, compositions and medicinal applications thereof |
| US9499522B2 (en) * | 2013-03-15 | 2016-11-22 | Blueprint Medicines Corporation | Compositions useful for treating disorders related to kit |
| WO2015092819A2 (en) * | 2013-12-21 | 2015-06-25 | Nektar Therapeutics (India) Pvt. Ltd. | Derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5- amine |
| ES2699354T3 (es) | 2014-01-17 | 2019-02-08 | Novartis Ag | Derivados de 1-(triazin-3-il/piridazin-3-il)-piper(-azin)idina y composiciones de las mismas para inhibir la actividad de SHP2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| SG11201609033TA (en) | 2014-05-01 | 2016-11-29 | Celgene Quanticel Res Inc | Inhibitors of lysine specific demethylase-1 |
| US10174032B2 (en) | 2014-05-05 | 2019-01-08 | Signalrx Pharmaceuticals, Inc. | Heterocyclic compound classes for signaling modulation |
| CN112625028B (zh) | 2015-06-19 | 2024-10-29 | 诺华股份有限公司 | 用于抑制shp2活性的化合物和组合物 |
| JP6878316B2 (ja) | 2015-06-19 | 2021-05-26 | ノバルティス アーゲー | Ｓｈｐ２の活性を阻害するための化合物および組成物 |
| WO2016203404A1 (en) | 2015-06-19 | 2016-12-22 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
-
2015
- 2015-01-16 WO PCT/IB2015/050343 patent/WO2015107493A1/en not_active Ceased
- 2015-01-16 JP JP2016547026A patent/JP6523303B2/ja active Active
- 2015-01-16 ES ES15703105T patent/ES2699351T3/es active Active
- 2015-01-16 US US15/110,498 patent/US10093646B2/en active Active
- 2015-01-16 CN CN201580004216.8A patent/CN105899491B/zh active Active
- 2015-01-16 EP EP15703105.5A patent/EP3094627B1/en active Active
-
2018
- 2018-08-30 US US16/117,674 patent/US10774065B2/en active Active
-
2020
- 2020-08-06 US US16/987,322 patent/US11401259B2/en active Active
-
2022
- 2022-06-24 US US17/808,895 patent/US20220348553A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US10093646B2 (en) | 2018-10-09 |
| JP2017503000A (ja) | 2017-01-26 |
| US11401259B2 (en) | 2022-08-02 |
| US10774065B2 (en) | 2020-09-15 |
| US20180362496A1 (en) | 2018-12-20 |
| CN105899491B (zh) | 2019-04-02 |
| CN105899491A (zh) | 2016-08-24 |
| US20200369643A1 (en) | 2020-11-26 |
| WO2015107493A1 (en) | 2015-07-23 |
| ES2699351T3 (es) | 2019-02-08 |
| US20170204080A1 (en) | 2017-07-20 |
| EP3094627A1 (en) | 2016-11-23 |
| EP3094627B1 (en) | 2018-08-22 |
| US20220348553A1 (en) | 2022-11-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11401259B2 (en) | 1-Pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2 | |
| JP7278359B2 (ja) | Ｓｈｐ２の活性を阻害するための化合物および組成物 | |
| JP7146016B2 (ja) | Ｓｈｐ２の活性を阻害するための化合物および組成物 | |
| JP6718889B2 (ja) | Ｓｈｐ２の活性を阻害するための化合物および組成物 | |
| US10301278B2 (en) | 1-(triazin-3-yl/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions therefor for inhibiting the activity of SHP2 | |
| JP6534389B2 (ja) | Ｓｈｐ２の活性を阻害するためのｎ−アザスピロシクロアルカン置換ｎ−ヘテロアリール化合物および組成物 | |
| BR112018075663B1 (pt) | Compostos para inibição da atividade de shp2, seu uso, e composição farmacêutica |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180110 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180110 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180918 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180913 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181217 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190122 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190312 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190416 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190425 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6523303 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |