CA3024706A1 - Heterocyclic inhibitors of ptpn11 - Google Patents
Heterocyclic inhibitors of ptpn11 Download PDFInfo
- Publication number
- CA3024706A1 CA3024706A1 CA3024706A CA3024706A CA3024706A1 CA 3024706 A1 CA3024706 A1 CA 3024706A1 CA 3024706 A CA3024706 A CA 3024706A CA 3024706 A CA3024706 A CA 3024706A CA 3024706 A1 CA3024706 A1 CA 3024706A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- recited
- mmol
- optionally substituted
- 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.)
- Pending
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- 239000003112 inhibitor Substances 0.000 title abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 371
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- 230000001404 mediated effect Effects 0.000 claims abstract description 20
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- 125000005843 halogen group Chemical group 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 64
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 52
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- 150000003839 salts Chemical class 0.000 claims description 49
- 125000005842 heteroatom Chemical group 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 42
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- 125000000217 alkyl group Chemical group 0.000 claims description 34
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 34
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
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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
- C07D487/02—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
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
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| US201662343455P | 2016-05-31 | 2016-05-31 | |
| US62/343,455 | 2016-05-31 | ||
| US201762451432P | 2017-01-27 | 2017-01-27 | |
| US62/451,432 | 2017-01-27 | ||
| PCT/US2017/034806 WO2017210134A1 (en) | 2016-05-31 | 2017-05-26 | Heterocyclic inhibitors of ptpn11 |
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| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| CN113750101A (zh) | 2015-12-10 | 2021-12-07 | Ptc医疗公司 | 用于治疗亨廷顿病的方法 |
| 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 |
| 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 |
| 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 |
| US11407753B2 (en) | 2017-06-05 | 2022-08-09 | Ptc Therapeutics, Inc. | Compounds for treating Huntington's disease |
| EP3645121B8 (en) | 2017-06-28 | 2025-06-18 | PTC Therapeutics, Inc. | Methods for treating huntington's disease |
| CA3067591A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | Methods for treating huntington's disease |
| EP3687997A1 (en) | 2017-09-29 | 2020-08-05 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| 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 |
| WO2019165073A1 (en) * | 2018-02-21 | 2019-08-29 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| MX2020008754A (es) | 2018-03-02 | 2020-12-07 | Otsuka Pharma Co Ltd | Compuestos farmaceuticos. |
| US20220315586A1 (en) | 2018-03-21 | 2022-10-06 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| WO2019183364A1 (en) * | 2018-03-21 | 2019-09-26 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine shp2 phosphatase inhibitors and methods of use thereof |
| KR20210005559A (ko) | 2018-03-27 | 2021-01-14 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 화합물 |
| US10954243B2 (en) * | 2018-05-02 | 2021-03-23 | Navire Pharma, Inc. | Substituted heterocyclic inhibitors of PTPN11 |
| LT3814357T (lt) * | 2018-06-27 | 2024-06-25 | Ptc Therapeutics, Inc. | Heterocikliniai ir heteroarilų junginiai, skirti hantingtono ligos gydymui |
| US11685746B2 (en) | 2018-06-27 | 2023-06-27 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating Huntington's disease |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| 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 |
| EP3860717A1 (en) | 2018-10-03 | 2021-08-11 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| CN111295384B (zh) * | 2018-10-10 | 2022-08-12 | 江苏豪森药业集团有限公司 | 双环类衍生物抑制剂、其制备方法和应用 |
| EP3867238B1 (en) | 2018-10-17 | 2023-06-07 | Array BioPharma Inc. | Protein tyrosine phosphatase inhibitors |
| US20230096028A1 (en) | 2019-03-01 | 2023-03-30 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| US20230148450A9 (en) | 2019-03-01 | 2023-05-11 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| PH12021552227A1 (en) | 2019-04-02 | 2022-05-30 | Array Biopharma Inc | Protein tyrosine phosphatase inhibitors |
| 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 |
| CA3154862A1 (en) | 2019-09-24 | 2021-04-01 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of making and using the same |
| 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 |
| CN115894606A (zh) | 2019-11-04 | 2023-04-04 | 锐新医药公司 | Ras抑制剂 |
| 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 |
| WO2021247836A1 (en) * | 2020-06-03 | 2021-12-09 | Board Of Regents, The University Of Texas System | Methods for targeting shp-2 to overcome resistance |
| 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 |
| 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 |
| 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 |
| EP4333850A4 (en) * | 2021-05-05 | 2025-04-09 | Huyabio International, LLC | SHP2 INHIBITOR MONOTHERAPY AND ITS USES |
| WO2022235817A1 (en) | 2021-05-05 | 2022-11-10 | Huabio International, Llc | Combination therapies comprising shp2 inhibitors and pd-1 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 |
| CA3217393A1 (en) | 2021-05-05 | 2022-11-10 | Elena S. Koltun | Ras inhibitors |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| CN114213417B (zh) * | 2021-11-16 | 2023-08-22 | 郑州大学 | 吡唑并六元氮杂环类化合物及其合成方法和应用 |
| 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 |
| CN117088887A (zh) * | 2022-05-20 | 2023-11-21 | 安徽中科拓苒药物科学研究有限公司 | Shp2抑制剂及其用途 |
| 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 |
| TWI879384B (zh) * | 2023-01-16 | 2025-04-01 | 大陸商上海美悅生物科技發展有限公司 | 雜環取代的吡嗪類化合物及其製備方法和用途 |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| 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 |
| 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 |
| 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 |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| 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 (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005028480A2 (en) | 2003-09-03 | 2005-03-31 | Neurogen Corporation | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
| MXPA06009462A (es) | 2004-02-27 | 2007-03-15 | Hoffmann La Roche | Derivados pirazolo heteroaril fusionados. |
| EP1732541A4 (en) | 2004-04-07 | 2008-03-05 | Takeda Pharmaceutical | CYCLIC COMPOUNDS |
| US20060122185A1 (en) | 2004-11-22 | 2006-06-08 | Jeremy Green | Bicyclic inhibitors of Rho kinase |
| GB0427604D0 (en) | 2004-12-16 | 2005-01-19 | Novartis Ag | Organic compounds |
| GB0506147D0 (en) | 2005-03-24 | 2005-05-04 | Merck Sharp & Dohme | Therapeutic agents |
| WO2008061109A2 (en) | 2006-11-15 | 2008-05-22 | Forest Laboratories Holdings Limited | Indazole derivatives useful as melanin concentrating receptor ligands |
| AR073412A1 (es) | 2008-10-03 | 2010-11-03 | Schering Corp | Derivados de espiro imidazolona como antagonistas del receptor glucagon y composiciones que los comprende. |
| JP2010111624A (ja) | 2008-11-06 | 2010-05-20 | Shionogi & Co Ltd | Ｔｔｋ阻害作用を有するインダゾール誘導体 |
| KR20110049217A (ko) | 2009-11-04 | 2011-05-12 | 다우어드밴스드디스플레이머티리얼 유한회사 | 신규한 유기 발광 화합물 및 이를 채용하고 있는 유기 전계 발광 소자 |
| JP2011246389A (ja) | 2010-05-26 | 2011-12-08 | Oncotherapy Science Ltd | Ｔｔｋ阻害作用を有する縮環ピラゾール誘導体 |
| WO2012106343A2 (en) | 2011-02-01 | 2012-08-09 | The Board Of Trustees Of The University Of Illinois | Hdac inhibitors and therapeutic methods using the same |
| WO2013052263A2 (en) | 2011-09-16 | 2013-04-11 | Microbiotix, Inc. | Antifungal compounds |
| WO2013040527A1 (en) | 2011-09-16 | 2013-03-21 | Microbiotix, Inc. | Antimicrobial compounds |
| US9738610B2 (en) | 2012-09-24 | 2017-08-22 | Whitehead Institute For Biomedical Research | Indazole derivatives and uses thereof |
| EP2988741B1 (en) | 2013-04-26 | 2019-11-27 | Indiana University Research&Technology Corporation | Hydroxyindole carboxylic acid based inhibitors for oncogenic src homology-2 domain containing protein tyrosine phosphatase-2 (shp2) |
| US9850276B2 (en) | 2013-05-24 | 2017-12-26 | The Scripps Research Institute | Bidentate-binding modulators of LRRK2 and JNK kinases |
| WO2015099481A1 (ko) | 2013-12-27 | 2015-07-02 | 주식회사 두산 | 유기 전계 발광 소자 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| 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 |
| WO2015107493A1 (en) * | 2014-01-17 | 2015-07-23 | Novartis Ag | 1 -pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2 |
| KR101998435B1 (ko) | 2014-06-09 | 2019-07-09 | 주식회사 두산 | 유기 전계 발광 소자 |
| KR101708097B1 (ko) | 2014-10-22 | 2017-02-17 | 주식회사 두산 | 유기 전계 발광 소자 |
| EP3273959A1 (en) | 2015-03-25 | 2018-01-31 | Novartis Ag | Pharmaceutical combinations |
| WO2016203404A1 (en) * | 2015-06-19 | 2016-12-22 | Novartis Ag | Compounds and compositions for inhibiting the activity of 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 |
| WO2017156397A1 (en) | 2016-03-11 | 2017-09-14 | Board Of Regents, The University Of Texas Sysytem | Heterocyclic inhibitors of ptpn11 |
| 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 |
| WO2019152454A1 (en) | 2018-01-30 | 2019-08-08 | Research Development Foundation | Shp2 inhibitors and methods of use thereof |
| 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 |
| WO2019165073A1 (en) | 2018-02-21 | 2019-08-29 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| MX2020008754A (es) | 2018-03-02 | 2020-12-07 | Otsuka Pharma Co Ltd | Compuestos farmaceuticos. |
| 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 |
| WO2019183364A1 (en) | 2018-03-21 | 2019-09-26 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine 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 |
| 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 |
| US20210230300A1 (en) | 2018-06-04 | 2021-07-29 | Bayer Aktiengesellschaft | Inhibitors of shp2 |
| 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 |
| TWI825144B (zh) | 2018-08-10 | 2023-12-11 | 美商思達利醫藥公司 | 第二型轉麩醯胺酸酶(tg2)抑制劑 |
| WO2020113213A2 (en) | 2018-11-30 | 2020-06-04 | Comet Therapeutics, Inc. | Cyclic pantetheine derivatives and uses thereof |
| AR117200A1 (es) | 2018-11-30 | 2021-07-21 | Syngenta Participations Ag | Derivados de tiazol microbiocidas |
| AR117183A1 (es) | 2018-11-30 | 2021-07-14 | Syngenta Crop Protection Ag | Derivados de tiazol microbiocidas |
| AU2019390729B2 (en) | 2018-11-30 | 2022-08-11 | Glaxosmithkline Intellectual Property Development Limited | Compounds useful in HIV therapy |
| JOP20210117A1 (ar) | 2018-11-30 | 2023-01-30 | Merck Sharp & Dohme | مشتقات أمينو ترايازولو كوينازولين بها استبدال في الموضع-9 كمضادات مستقبل أدينوزين، تركيبات صيدلانية واستخدامها |
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| JP7044375B2 (ja) | 2022-03-30 |
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| US20190270746A1 (en) | 2019-09-05 |
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