JP6916279B2 - アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン - Google Patents

アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン Download PDF

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JP6916279B2
JP6916279B2 JP2019522611A JP2019522611A JP6916279B2 JP 6916279 B2 JP6916279 B2 JP 6916279B2 JP 2019522611 A JP2019522611 A JP 2019522611A JP 2019522611 A JP2019522611 A JP 2019522611A JP 6916279 B2 JP6916279 B2 JP 6916279B2
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cycloalkyl
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JP2019527728A5 (enExample
JP2019527728A (ja
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アシュトッシュ・ジョガルカー
ウォルター・ウォン
エレナ・エス・コルトン
アドリアン・ジル
ケヴィン・メレム
ナイン・エーイ
アンドレアス・バックル
クリストファー・セムコ
ガート・キス
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Revolution Medicines Inc
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    • 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
    • C07D241/20—Nitrogen atoms
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C07D241/18—Oxygen or sulfur 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
    • C07D401/02—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
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • C07D403/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • 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
    • 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
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
    • C07D477/26—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 4
    • 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
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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

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  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
JP2019522611A 2016-07-12 2017-07-11 アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン Active JP6916279B2 (ja)

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JP2021116788A JP7416740B2 (ja) 2016-07-12 2021-07-15 アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン
JP2023177195A JP7861313B2 (ja) 2016-07-12 2023-10-13 アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン

Applications Claiming Priority (5)

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US201662361249P 2016-07-12 2016-07-12
US62/361,249 2016-07-12
US201762449523P 2017-01-23 2017-01-23
US62/449,523 2017-01-23
PCT/US2017/041577 WO2018013597A1 (en) 2016-07-12 2017-07-11 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors

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JP2021116788A Active JP7416740B2 (ja) 2016-07-12 2021-07-15 アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン
JP2023177195A Active JP7861313B2 (ja) 2016-07-12 2023-10-13 アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン

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JP2023177195A Active JP7861313B2 (ja) 2016-07-12 2023-10-13 アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン

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Families Citing this family (158)

* Cited by examiner, † Cited by third party
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
JO3517B1 (ar) 2014-01-17 2020-07-05 Novartis Ag ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
WO2017210134A1 (en) 2016-05-31 2017-12-07 Board Of Regents, University Of Texas System Heterocyclic inhibitors of ptpn11
KR102218333B1 (ko) 2016-06-07 2021-02-22 자코바이오 파마슈티칼스 컴퍼니 리미티드 Shp2 억제제로서 유용한 신규한 헤테로환형 유도체
PT3468972T (pt) 2016-06-14 2020-08-21 Novartis Ag Compostos e composições para inibir a atividade da shp2
IL311645B2 (en) 2016-07-12 2025-11-01 Revolution Medicines Inc 2,5- disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines asallosteric shp2 inhibitors
EP3515916B1 (en) 2016-09-22 2023-06-07 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
TW202500565A (zh) 2016-10-24 2025-01-01 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
CA3051054A1 (en) 2017-01-23 2018-07-26 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
CN110446709B (zh) 2017-01-23 2023-09-12 锐新医药公司 作为变构shp2抑制剂的二环化合物
SG11201908820VA (en) * 2017-03-23 2019-10-30 Jacobio Pharmaceuticals Co Ltd Novel heterocyclic derivatives useful as shp2 inhibitors
BR102018007822A2 (pt) 2017-04-20 2018-11-06 Gilead Sciences, Inc. composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição
US11591336B2 (en) 2017-05-26 2023-02-28 D. E. Shaw Research, Llc Substituted pyrazolo[3,4-b]pyrazines as SHP2 phosphatase inhibitors
TWI852912B (zh) 2017-09-07 2024-08-21 美商銳新醫藥公司 Shp2抑制劑組合物以及治療癌症的方法
JP7447002B2 (ja) 2017-09-11 2024-03-11 クルーゾン・ファーマシューティカルズ・インコーポレイテッド ＳＨＰ２のオクタヒドロシクロペンタ［ｃ］ピロールのアロステリック阻害剤
EP3687997A1 (en) 2017-09-29 2020-08-05 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors
BR112020007058A2 (pt) * 2017-10-12 2020-10-06 Revolution Medicines, Inc. compostos de piridina, pirazina, e triazina como inibidores de shp2 alostéricos
BR112020009757A2 (pt) 2017-12-15 2020-11-03 Revolution Medicines, Inc. compostos policíclicos como inibidores alostéricos de shp2
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
US11498930B2 (en) 2018-02-13 2022-11-15 Blueray Therapeutics (Shanghai) Co., Ltd Pyrimidine-fused cyclic compound, preparation method therefor and application thereof
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
WO2019160882A1 (en) 2018-02-13 2019-08-22 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
RU2020133727A (ru) * 2018-03-21 2022-04-21 Сучжоу Пухе Биофарма Ко., Лтд. Ингибиторы shp2 и их применение
US12138263B2 (en) 2018-03-21 2024-11-12 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine SHP2 phosphatase inhibitors and methods of use thereof
CN117263942A (zh) * 2018-03-21 2023-12-22 传达治疗有限公司 Shp2磷酸酶抑制剂及其使用方法
KR20200143417A (ko) 2018-04-10 2020-12-23 레볼루션 메디슨즈, 인크. Shp2 억제제 조성물, 암을 치료하는 방법 및 shp2 돌연변이를 갖는 대상체를 확인하는 방법
KR102611661B1 (ko) * 2018-05-02 2023-12-08 나비레 파르마, 인코퍼레이티드 Ptpn11의 치환된 헤테로사이클릭 억제제
PE20210642A1 (es) 2018-07-13 2021-03-23 Gilead Sciences Inc Inhibidores de pd-1/pd-l1
PL3833670T3 (pl) 2018-08-10 2024-08-19 Navire Pharma, Inc. Pochodne 6-(4-amino-3-metylo-2-oksa-8-azaspiro[4.5]dekan-8-ylo)-3-(2,3-dichlorofenylo)-2-metylopirymidyn-4(3h)-onu oraz powiązane związki jako inhibitory ptpn11 (shp2) do leczenia raka
JP7337174B2 (ja) 2018-09-18 2023-09-01 ニカング セラピューティクス， インコーポレイテッド Ｓｒｃホモロジー－２ホスファターゼ阻害剤としての三置換ヘテロアリール誘導体
CN112839935A (zh) * 2018-09-26 2021-05-25 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
IL304526B2 (en) 2018-09-29 2025-05-01 Novartis Ag Production of compounds and preparations for inhibiting the activity of SHP2
EP3860717A1 (en) 2018-10-03 2021-08-11 Gilead Sciences, Inc. Imidozopyrimidine derivatives
JP2022508651A (ja) * 2018-10-08 2022-01-19 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 癌を処置するためのｓｈｐ２阻害剤組成物および方法
TW202028183A (zh) * 2018-10-10 2020-08-01 大陸商江蘇豪森藥業集團有限公司 含氮雜芳類衍生物調節劑、其製備方法和應用
MA53921A (fr) 2018-10-17 2022-01-26 Array Biopharma Inc Inhibiteurs de protéine tyrosine phosphatase
CN109265352B (zh) * 2018-10-31 2021-06-04 杭州迈世腾药物科技有限公司 芳基环丙基醚及其衍生物的制备方法
WO2020108590A1 (zh) 2018-11-30 2020-06-04 上海拓界生物医药科技有限公司 嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用
CN113316574B (zh) * 2019-01-31 2024-01-30 贝达药业股份有限公司 Shp2抑制剂及其应用
US20230096028A1 (en) 2019-03-01 2023-03-30 Revolution Medicines, Inc. Bicyclic heterocyclyl compounds and uses thereof
WO2020180768A1 (en) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Bicyclic heteroaryl compounds and uses thereof
CN111647000B (zh) * 2019-03-04 2021-10-12 勤浩医药（苏州）有限公司 吡嗪类衍生物及其在抑制shp2中的应用
US11033547B2 (en) 2019-03-07 2021-06-15 Merck Patent Gmbh Carboxamide-pyrimidine derivatives as SHP2 antagonists
AU2020251841B2 (en) * 2019-04-02 2025-01-30 Array Biopharma Inc. Protein tyrosine phosphatase inhibitors
CN113646049B (zh) 2019-04-08 2024-08-13 默克专利有限公司 作为shp2拮抗剂的嘧啶酮衍生物
CA3142430A1 (en) * 2019-06-07 2020-12-10 Revolution Medicines, Inc. Solid forms of {6-[(2-amino-3-chloropyridin-4-yl)sulfanyl]-3-[(3s,4s)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-5-methylpyrazin-2-yl}methanol, an shp2 inhibitor
US20220380385A1 (en) 2019-06-28 2022-12-01 Tuojie Biotech(Shanghai) Co., Ltd. Pyrimidine five-membered nitrogen heterocyclic derivative, preparation method thereof and pharmaceutical use thereof
CN111704611B (zh) * 2019-07-25 2022-01-14 上海凌达生物医药有限公司 一类芳基螺环类shp2抑制剂化合物、制备方法和用途
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
WO2021043077A1 (zh) * 2019-09-06 2021-03-11 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
CN114502165A (zh) * 2019-09-23 2022-05-13 苏州浦合医药科技有限公司 Shp2抑制剂及其用途
EP4034539A1 (en) 2019-09-24 2022-08-03 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
US20240139193A1 (en) 2019-10-15 2024-05-02 Amgen Inc. Combination therapy of kras inhibitor and shp2 inhibitor for treatment of cancers
CN121471132A (zh) 2019-11-04 2026-02-06 锐新医药公司 Ras抑制剂
WO2021091956A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
MX2022005359A (es) * 2019-11-04 2022-06-02 Revolution Medicines Inc Inhibidores de ras.
PH12022551102A1 (en) 2019-11-08 2023-11-20 Revolution Medicines Inc Bicyclic heteroaryl compounds and uses thereof
CN114980976A (zh) 2019-11-27 2022-08-30 锐新医药公司 共价ras抑制剂及其用途
EP4069301A1 (en) 2019-12-04 2022-10-12 Bayer Aktiengesellschaft Inhibitors of shp2
CA3163703A1 (en) * 2020-01-07 2021-07-15 Steve Kelsey Shp2 inhibitor dosing and methods of treating cancer
WO2021143680A1 (zh) 2020-01-16 2021-07-22 浙江海正药业股份有限公司 杂芳基类衍生物及其制备方法和用途
CN113135910A (zh) * 2020-01-19 2021-07-20 北京诺诚健华医药科技有限公司 嘧啶-4(3h)-酮类杂环化合物、其制备方法及其在医药学上的应用
WO2021147879A1 (zh) * 2020-01-21 2021-07-29 贝达药业股份有限公司 Shp2抑制剂及其应用
US20230090389A1 (en) 2020-02-28 2023-03-23 Novartis Ag A triple pharmaceutical combination comprising dabrafenib, an erk inhibitor and a shp2 inhibitor
CN113493440B (zh) * 2020-04-03 2024-08-23 上海翰森生物医药科技有限公司 含氮杂芳类衍生物的盐及其晶型
TW202144334A (zh) * 2020-04-03 2021-12-01 大陸商上海翰森生物醫藥科技有限公司 含氮雜芳類衍生物游離鹼的晶型
CN115362149B (zh) * 2020-04-26 2024-05-14 贝达药业股份有限公司 Shp2抑制剂及其组合物和应用
CN115515946A (zh) * 2020-06-11 2022-12-23 贝达药业股份有限公司 Shp2抑制剂及其组合物和应用
CN115916194A (zh) 2020-06-18 2023-04-04 锐新医药公司 用于延迟、预防和治疗针对ras抑制剂的获得性抗性的方法
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
ES3040751T3 (en) 2020-07-08 2025-11-04 Novartis Ag Manufacture of compounds and compositions for inhibiting the activity of shp2
CN116113418A (zh) * 2020-08-25 2023-05-12 四川科伦博泰生物医药股份有限公司 杂环化合物及其制备方法和用途
EP4208261A1 (en) 2020-09-03 2023-07-12 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
IL301298A (en) 2020-09-15 2023-05-01 Revolution Medicines Inc Indole derivatives as RAS inhibitors in cancer therapy
JP7654071B2 (ja) 2020-10-20 2025-03-31 アムジエン・インコーポレーテツド 複素環スピロ化合物及び使用方法
WO2022093856A1 (en) 2020-10-27 2022-05-05 Amgen Inc. Heterocyclic spiro compounds and methods of use
WO2022133217A1 (en) * 2020-12-18 2022-06-23 Genzyme Corporation Process for preparing shp2 inhibitors
CN116848121A (zh) * 2020-12-18 2023-10-03 建新公司 制备shp2抑制剂的方法
AU2021409816A1 (en) 2020-12-22 2023-07-06 Qilu Regor Therapeutics Inc. Sos1 inhibitors and uses thereof
WO2022161222A1 (zh) * 2021-01-29 2022-08-04 四川科伦博泰生物医药股份有限公司 一类杂环类shp2抑制剂、其制备方法及用途
EP4039685A1 (en) 2021-02-08 2022-08-10 Irbm S.P.A. Azabicyclic shp2 inhibitors
WO2022206684A1 (zh) * 2021-03-31 2022-10-06 南京明德新药研发有限公司 一系列含Se的吡嗪类化合物及其应用
MX2023011664A (es) * 2021-04-01 2023-10-11 Array Biopharma Inc Forma cristalina de un inhibidor de shp2.
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
EP4329888A1 (en) 2021-04-29 2024-03-06 Amgen Inc. 2-aminobenzothiazole compounds and methods of use thereof
CA3217084A1 (en) 2021-05-05 2022-11-10 Farbod Shojaei Combination therapies comprising shp2 inhibitors and pd-1 inhibitors
CN117642167A (zh) * 2021-05-05 2024-03-01 沪亚生物国际有限责任公司 Shp2抑制剂单一疗法及其用途
WO2022235822A1 (en) * 2021-05-05 2022-11-10 Huabio International, Llc Shp2 inhibitor monotherapy and uses thereof
IL308195A (en) 2021-05-05 2024-01-01 Revolution Medicines Inc RAS inhibitors for cancer treatment
PE20240088A1 (es) 2021-05-05 2024-01-16 Revolution Medicines Inc Inhibidores de ras
WO2022235866A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Covalent ras inhibitors and uses thereof
CN117177752A (zh) 2021-05-05 2023-12-05 诺华股份有限公司 用于治疗mpnst的化合物和组合物
JP7656087B2 (ja) * 2021-05-13 2025-04-02 中国科学院上海薬物研究所 Ｓｈｐ２活性を阻害する複素環化合物、その製造方法および使用
EP4342891A4 (en) 2021-05-21 2025-05-14 CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. SPIRO CONNECTION AND USE THEREOF
TW202313041A (zh) 2021-06-09 2023-04-01 瑞士商諾華公司 包含達拉菲尼、曲美替尼和shp2抑制劑之三重藥物組合
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
WO2023282702A1 (ko) * 2021-07-09 2023-01-12 주식회사 카나프테라퓨틱스 Shp2 억제제 및 이의 용도
CN113636952B (zh) * 2021-07-19 2023-07-21 河南农业大学 一种制备4-溴苯甲酰胺的方法
JP2024528949A (ja) * 2021-08-09 2024-08-01 ユービックス セラピューティクス インコーポレイテッド Ｓｈｐ２タンパク質分解活性を有する化合物及びその医薬用途
US20240374571A1 (en) 2021-09-01 2024-11-14 Novartis Ag Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers
WO2023046198A1 (zh) * 2021-09-27 2023-03-30 中国医药研究开发中心有限公司 磺胺酮类化合物及其制备方法和医药用途
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
WO2023122938A1 (en) * 2021-12-28 2023-07-06 Js Innomed Holdings Ltd. Heterocyclic compounds as shp2 inhibitors, compositions comprising the heterocyclic compound, and methods of use thereof
JP2025508702A (ja) 2022-02-16 2025-04-10 アムジエン・インコーポレーテツド キナゾリン化合物、及び変異ｋｒａｓタンパク質の阻害剤としてのその使用
CN118715215A (zh) 2022-02-16 2024-09-27 美国安进公司 作为突变kras蛋白抑制剂的喹唑啉化合物及其用途
CN119136805A (zh) 2022-03-04 2024-12-13 伊莱利利公司 包括kras g12c抑制剂和shp2抑制剂的治疗方法
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023169170A1 (zh) * 2022-03-10 2023-09-14 捷思英达控股有限公司 作为shp2抑制剂的杂环化合物、包括该杂环化合物的组合物、及其使用方法
US20250134885A1 (en) 2022-03-21 2025-05-01 Institut National de la Santé et de la Recherche Médicale Use of shp2 inhibitors for inhibiting senescence
TW202402761A (zh) * 2022-03-28 2024-01-16 美商健臻公司 製備shp2抑制劑的方法
CN119768393A (zh) 2022-05-25 2025-04-04 医肯纳肿瘤学公司 Mek抑制剂和其用途
EP4536364A1 (en) 2022-06-10 2025-04-16 Revolution Medicines, Inc. Macrocyclic ras inhibitors
US20260144793A1 (en) 2022-07-11 2026-05-28 Amgen Inc. Methods of treating cancer
JP2025528836A (ja) 2022-08-17 2025-09-02 ツリーライン バイオサイエンシズ インコーポレイテッド ピリドピリミジンＫＲａｓ阻害剤
EP4345101A1 (en) 2022-09-29 2024-04-03 Irbm S.P.A. Azole derivatives as shp2 inhibitors
WO2024085699A1 (ko) * 2022-10-19 2024-04-25 주식회사 유빅스테라퓨틱스 Shp2 단백질 분해용 화합물 및 이들의 의약 용도
JP2025539080A (ja) 2022-11-14 2025-12-03 アムジエン・インコーポレーテツド 大環状ｋｒａｓ阻害剤及び使用方法
WO2024113194A1 (en) * 2022-11-30 2024-06-06 Canwell Biotech Limited Shp2 inhibitors, compositions and methods thereof
CN121487738A (zh) 2023-03-30 2026-02-06 锐新医药公司 诱导ras gtp水解的组合物和其用途
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
CN121487951A (zh) 2023-04-07 2026-02-06 锐新医药公司 大环ras抑制剂
EP4695261A1 (en) 2023-04-14 2026-02-18 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
AU2024251341A1 (en) 2023-04-14 2025-10-16 Revolution Medicines, Inc. Crystalline forms of a ras inhibitor
KR20260019479A (ko) 2023-05-04 2026-02-10 레볼루션 메디슨즈, 인크. Ras 관련 질환 또는 장애를 위한 병용 요법
CN121889155A (zh) 2023-08-07 2026-04-17 锐新医药公司 用于治疗ras蛋白相关疾病或病症的rmc-6291
WO2025064848A1 (en) 2023-09-21 2025-03-27 Treeline Biosciences, Inc. Spirocyclic dihydropyranopyridine kras inhibitors
AU2024360465A1 (en) 2023-10-12 2026-04-09 Revolution Medicines, Inc. Macrocyclic ras inhibitors
WO2025081291A1 (en) * 2023-10-16 2025-04-24 Canwell Biotech Limited Benzo [c] [1, 2] oxaborol-1 (3h) -ol derivatives as shp2 inhibitors, compositions and methods thereof
AU2024404879A1 (en) 2023-12-22 2026-06-25 Regor Pharmaceuticals, Inc. Sos1 inhibitors and uses thereof
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
TW202602882A (zh) 2024-03-14 2026-01-16 美商安進公司 作為ｋｒａｓ調節劑的大環化合物及其用途
WO2025194054A1 (en) 2024-03-14 2025-09-18 Amgen Inc. Spirocyclic compounds as modulators of kras and uses thereof
WO2025217247A1 (en) 2024-04-10 2025-10-16 Amgen Inc. Tethered spiro-heterocyclic inhibitors of kras g12c mutant proteins and uses thereof
WO2025230878A1 (en) 2024-04-29 2025-11-06 Amgen Inc. Macrocyclic compounds as modulators of kras and uses thereof
WO2025240582A1 (en) 2024-05-14 2025-11-20 Amgen Inc. Macrocyclic compounds as modulators of kras and uses thereof
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025245127A1 (en) 2024-05-21 2025-11-27 Treeline Biosciences, Inc. Spirocyclic dihydropyranopyrimidine kras inhibitors
US20250375445A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026055477A1 (en) 2024-09-06 2026-03-12 Amgen Inc. Macrocyclic compounds as modulators of kras and uses thereof
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer
US20260108528A1 (en) 2024-10-22 2026-04-23 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2026106912A1 (en) 2024-11-12 2026-05-21 Revolution Medicines, Inc. Ras inhibitors
WO2026112260A1 (en) 2024-11-21 2026-05-28 Revolution Medicines, Inc. Ras inhibitors
WO2026122764A2 (en) 2024-12-06 2026-06-11 Revolution Medicines, Inc. Ras inhibitors
WO2026128688A2 (en) 2024-12-13 2026-06-18 Revolution Medicines, Inc. Ras inhibitors
CN119661551B (zh) * 2024-12-16 2025-11-25 重庆大学 一种(3r,4s)-3-甲基-2-氧杂-8-氮杂螺[4.5]癸烷-4-胺盐酸盐的制备方法
WO2026161839A1 (en) 2025-01-27 2026-07-30 Revolution Medicines, Inc. Ras inhibitors

Family Cites Families (125)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2572728A (en) * 1949-01-07 1951-10-23 American Cyanamid Co Hydroxybenzenesulfonamidopyra-zines and preparation of same
US2636882A (en) 1950-08-11 1953-04-28 Quaker Oats Co Preparation of 3-pyridols from 2-acylfurans
BE758503A (fr) 1969-11-07 1971-05-05 Shell Int Research Compositions pesticides
GB1459571A (en) 1974-09-12 1976-12-22 Pfizer Ltd Thiophene-2-sulphonamide derivatives and their use as therapeutic agents sheet orienting apparatus
JPS5762269A (en) * 1980-10-03 1982-04-15 Ogawa Koryo Kk 2,3,5-trisubstituted pyrazine derivative
US4513135A (en) * 1982-03-05 1985-04-23 Eli Lilly And Company Diaryl-pyrazine derivatives affecting GABA binding
JPH0249775A (ja) 1988-05-19 1990-02-20 Nippon Soda Co Ltd ６員環又は７員環を有する複素環化合物及びその製造方法
JPH04112877A (ja) 1990-09-04 1992-04-14 Nippon Soda Co Ltd 新規シアノピラジン誘導体及びその製造方法
EP0579835A4 (en) 1991-11-12 1994-06-01 Nippon Soda Co Wavelength conversion material for agriculture
US5262564A (en) 1992-10-30 1993-11-16 Octamer, Inc. Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents
GB9504854D0 (en) 1994-03-31 1995-04-26 Zeneca Ltd Nitrogen derivatives
ES2168237T3 (es) 1996-02-07 2007-04-01 Neurocrine Biosciences, Inc. Pirazolopirimidinas como antagonistas de receptores de crf.
EP1007042A4 (en) * 1997-06-13 2001-07-04 Sugen Inc NEW HETEROCYCLIC COMPOUNDS FOR MODULATING THE PROTEIN-TYROSIN-ENZYME-RELATED CELLULAR SIGNAL TRANSDUCTION
DE60023920T2 (de) 1999-08-27 2006-07-20 Sugen, Inc., South San Francisco Phosphatmimetika und Verfahren zur Behandlung mit Phosphataseinhibitoren HIBITOREN
ATE307121T1 (de) 2000-02-16 2005-11-15 Neurogen Corp Substituierte arylpyrazine
TWI316055B (enExample) 2001-04-26 2009-10-21 Nippon Shinyaku Co Ltd
AU2002334773A1 (en) 2001-10-01 2003-04-14 Mount Sinai School Of Medicine Noonan syndrome gene
US6921762B2 (en) 2001-11-16 2005-07-26 Amgen Inc. Substituted indolizine-like compounds and methods of use
DE60234269D1 (de) 2001-11-21 2009-12-17 Pharmacia & Upjohn Co Llc Substituierte aryl 1,4-pyrazin derivate
EP1492784A4 (en) 2002-03-28 2006-03-29 Merck & Co Inc SUBSTITUTED 2,3-DIPHENYLPYRIDINES
BR0309551A (pt) 2002-04-26 2005-02-09 Upjohn Co Derivados substituìdos de pirazina
EP1539736A1 (en) * 2002-09-12 2005-06-15 Pharmacia & Upjohn Company LLC Substituted 1,4-pyrazine derivatives
ES2367430T3 (es) 2002-12-23 2011-11-03 Wyeth Llc Anticuerpos contra pd-1 y sus usos.
US7157460B2 (en) 2003-02-20 2007-01-02 Sugen Inc. Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors
MXPA05012082A (es) 2003-05-09 2006-02-22 Pharmacia & Upjohn Co Llc Compuestos como antagonistas del receptor crf1.
GB0314057D0 (en) * 2003-06-18 2003-07-23 Astrazeneca Ab Therapeutic agents
FR2856684B1 (fr) 2003-06-26 2008-04-11 Sanofi Synthelabo Derives de diphenylpyridine, leur preparation et leur application en therapeutique
US7326706B2 (en) * 2003-08-15 2008-02-05 Bristol-Myers Squibb Company Pyrazine modulators of cannabinoid receptors
AU2004274403A1 (en) 2003-09-03 2005-03-31 Aventis Pharmaceuticals Inc. 5-aryl-Pyrazolo(4,3-d)pyrimidines, pyridines, and pyrazines and related compounds
MXPA06004043A (es) 2003-10-10 2006-06-28 Pfizer Prod Inc 2h-[1,2,4]triazolo[4,3-a]pirazinas sustituidas como inhibidores de la glucogeno sintetasa cinasa 3.
CA2543644A1 (en) * 2003-10-27 2005-05-06 Astellas Pharma Inc. Pyrazine derivatives and pharmaceutical use thereof
DE102004015954A1 (de) * 2004-04-01 2005-11-10 Ina-Schaeffler Kg Umschlingungstrieb
EP1737841A1 (en) * 2004-04-01 2007-01-03 Astellas Pharma Inc. Pyrazine derivatives and pharmaceutical use thereof as adenosine antagonists
US20050282818A1 (en) 2004-06-22 2005-12-22 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
ES2375395T3 (es) 2004-12-23 2012-02-29 Mallinckrodt Llc Derivados de pirazina fluorescentes y método de uso de los mismos en la evaluación de la función renal.
EP1871762A2 (en) * 2005-04-18 2008-01-02 Neurogen Corporation Subtituted heteroaryl cb1 antagonists
MY153898A (en) 2005-06-22 2015-04-15 Plexxikon Inc Compounds and methods for kinase modulation, and indications therefor
US20080274469A1 (en) 2005-10-21 2008-11-06 The Regents Of The University Of California C-Kit Oncogene Mutations in Melanoma
EP1986701B1 (en) * 2006-02-24 2012-06-13 Mallinckrodt LLC Optical agents for use in surgery
US8987474B2 (en) 2006-04-07 2015-03-24 University Of South Florida Inhibition of Shp2/PTPN11 protein tyrosine phosphatase by NSC-87877, NSC-117199 and their analogs
JP2009535344A (ja) 2006-04-28 2009-10-01 ノースウェスタン ユニバーシティ 神経炎症性疾患の処置のためのピリダジン化合物を含む処方物
US7893058B2 (en) 2006-05-15 2011-02-22 Janssen Pharmaceutica Nv Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases
HRP20100378T1 (hr) 2006-05-31 2010-08-31 Galapagos N.V. Spojevi triazolopirazina učinkoviti za tretman degenerativnih i upalnih bolesti
JP2009539840A (ja) 2006-06-06 2009-11-19 シェーリング コーポレイション プロテインキナーゼ阻害剤としてのイミダゾピラジン
EP2131861A2 (en) 2007-03-01 2009-12-16 Mallinckrodt Inc. Integrated photoactive small molecules and uses thereof
DE602008005729D1 (en) 2007-04-06 2011-05-05 Novartis Ag Ä2,6-ünaphthyridine als proteinkinasehemmer
US8148369B2 (en) 2007-05-10 2012-04-03 Janssen Pharmaceutica Nv Fused pyrazine compounds useful for the treatment of degenerative and inflammatory diseases
WO2008138843A1 (en) 2007-05-10 2008-11-20 Galapagos N.V. Imidazopyridines and triazolopyrimidines useful for the treatment of joint degenerative & inflammatory diseases
WO2008156174A1 (ja) 2007-06-21 2008-12-24 Taisho Pharmaceutical Co., Ltd. ピラジンアミド化合物
CA2695621A1 (en) 2007-08-09 2009-02-12 Merck Sharp & Dohme Corp. Pyridine carboxamide orexin receptor antagonists
WO2009025823A1 (en) 2007-08-21 2009-02-26 Amgen Inc. Phosphodiesterase 10 inhibitors
JP2010031249A (ja) * 2008-06-23 2010-02-12 Sumitomo Chemical Co Ltd 組成物及び該組成物を用いてなる発光素子
WO2010011666A2 (en) 2008-07-21 2010-01-28 University Of South Florida Indoline scaffold shp-2 inhibitors and cancer treatment method
EP2349267B1 (en) 2008-10-30 2014-06-25 Merck Sharp & Dohme Corp. Pyridazine carboxamide orexin receptor antagonists
JP5590040B2 (ja) * 2008-11-12 2014-09-17 アリアド・ファーマシューティカルズ・インコーポレイテッド キナーゼ阻害剤としてのピラジノピラジンおよび誘導体
PL2389372T3 (pl) 2009-01-23 2016-02-29 Rigel Pharmaceuticals Inc Kompozycje i sposoby hamowania szlaku JAK
WO2010121212A2 (en) 2009-04-17 2010-10-21 H. Lee Moffit Cancer Center And Research Institute, Inc. Indoline scaffold shp-2 inhibitors and method of treating cancer
WO2010141275A1 (en) 2009-06-01 2010-12-09 Merck Sharp & Dohme Corp. Pyrazine carboxamide orexin receptor antagonists
NZ623069A (en) * 2009-08-17 2015-11-27 Sloan Kettering Inst Cancer Heat shock protein binding compounds, compositions, and methods for making and using same
WO2011026242A1 (en) 2009-09-03 2011-03-10 Vancouver Biotech Ltd. Monoclonal antibodies against gonadotropin-releasing hormone receptor
US8673913B2 (en) 2009-11-13 2014-03-18 Case Western Reserve University SHP-2 phosphatase inhibitor
CN102918061B (zh) 2010-03-05 2016-06-08 霍夫曼-拉罗奇有限公司 针对人csf-1r的抗体及其用途
AR081908A1 (es) 2010-05-11 2012-10-31 Sanofi Aventis N-heteroaril-espirolactama-bipirrolidinas sustituidas, preparacion y usos terapeuticos de las mismas
US8703768B2 (en) 2010-06-09 2014-04-22 Hoffmann-La Roche Inc. Nitrogen containing heteroaryl compounds
BR112013000946B1 (pt) 2010-07-14 2020-09-08 Novartis Ag Compostos heterocíclicos agonistas de receptor de ip, seus usos, composição e combinação farmacêuticas
GB201106829D0 (en) * 2011-04-21 2011-06-01 Proximagen Ltd Heterocyclic compounds
WO2012116237A2 (en) 2011-02-23 2012-08-30 Intellikine, Llc Heterocyclic compounds and uses thereof
US20120330012A1 (en) 2011-04-29 2012-12-27 Abbott Laboratories Novel Tricyclic Compounds
CN103181918B (zh) 2011-05-04 2014-10-29 厦门大学 脂肪酸类化合物在制备预防和治疗肝癌药物中的应用
EP2802583A1 (en) * 2012-01-13 2014-11-19 Novartis AG Fused piperidines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders
HUE033177T2 (en) * 2012-01-17 2017-11-28 Astellas Pharma Inc Pyrazine carboxamide compound
CA2881279C (en) 2012-08-07 2020-07-07 Merck Patent Gmbh Pyridopyrimidine derivatives as protein kinase inhibitors
WO2014072881A1 (en) 2012-11-08 2014-05-15 Pfizer Inc. Heteroaromatic compounds and their use as dopamine d1 ligands
AU2013352304C1 (en) 2012-11-29 2018-03-22 Chemocentryx, Inc. CXCR7 antagonists
WO2014113584A1 (en) 2013-01-16 2014-07-24 Rhode Island Hospital Compositions and methods for the prevention and treatment of osteolysis and osteoporosis
EP2953939A1 (en) * 2013-02-07 2015-12-16 Merck Patent GmbH Substituted quinoxaline derivatives and their use as positive allosteric modulators of mglur4
SG11201505896YA (en) 2013-02-20 2015-09-29 Novartis Ag Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor
WO2014165271A2 (en) 2013-03-13 2014-10-09 Neotope Biosciences Limited Tau immunotherapy
CN103554038B (zh) 2013-06-19 2015-10-14 云南大学 多卤代苯腈喹唑啉酮化合物及其制备方法和用途
WO2015107494A1 (en) * 2014-01-17 2015-07-23 Novartis Ag 1 -(triazin-3-yi_/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions thereof for inhibiting the activity of shp2
ES2699351T3 (es) * 2014-01-17 2019-02-08 Novartis Ag Derivados de 1-piridazin/triazin-3-il-piper(-azina)/idina/pirolidina 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
WO2016007731A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Imidazopyridines and imidazopyrazines as lsd1 inhibitors
SG10201900631TA (en) 2014-08-01 2019-02-27 Nuevolution As Compounds active towards bromodomains
ES2935114T3 (es) * 2014-09-05 2023-03-01 Celgene Quanticel Res Inc Inhibidores de la desmetilasa 1 específica de lisina
AU2015350315B2 (en) * 2014-11-18 2020-06-25 Merck Sharp & Dohme Corp. Aminopyrazine compounds with A2A antagonist properties
WO2016100116A1 (en) 2014-12-17 2016-06-23 Siemens Healthcare Diagnostics Inc. Sandwich assay design for small molecules
MX375970B (es) 2014-12-23 2025-03-06 Novartis Ag Compuestos de triazolopirimidina y usos de los mismos.
WO2016112295A1 (en) 2015-01-09 2016-07-14 Warp Drive Bio, Inc. Compounds that participate in cooperative binding and uses thereof
ES2730112T3 (es) * 2015-03-09 2019-11-08 Bristol Myers Squibb Co Lactamas como inhibidores de ROCK
EA201792205A1 (ru) 2015-04-03 2018-02-28 Инсайт Корпорейшн Гетероциклические соединения как ингибиторы lsd1
EP3310779B1 (en) 2015-06-19 2019-05-08 Novartis AG Compounds and compositions for inhibiting the activity of shp2
WO2016203406A1 (en) * 2015-06-19 2016-12-22 Novartis Ag Compounds and compositions for inhibiting the activity of shp2
ES2824576T3 (es) 2015-06-19 2021-05-12 Novartis Ag Compuestos y composiciones para inhibir la actividad de SHP2
WO2017011618A1 (en) 2015-07-15 2017-01-19 The Curators Of The University Of Missouri Targeted nanoparticle conjugate and method for co-delivery of sirna and drug
CA3000822A1 (en) 2015-10-01 2017-04-06 Warp Drive Bio, Inc. Methods and reagents for analyzing protein-protein interfaces
US11008372B2 (en) 2015-11-07 2021-05-18 Board Of Regents, The University Of Texas System Targeting proteins for degradation
WO2017156397A1 (en) 2016-03-11 2017-09-14 Board Of Regents, The University Of Texas Sysytem Heterocyclic inhibitors of ptpn11
KR102218333B1 (ko) * 2016-06-07 2021-02-22 자코바이오 파마슈티칼스 컴퍼니 리미티드 Shp2 억제제로서 유용한 신규한 헤테로환형 유도체
PT3468972T (pt) 2016-06-14 2020-08-21 Novartis Ag Compostos e composições para inibir a atividade da shp2
IL311645B2 (en) 2016-07-12 2025-11-01 Revolution Medicines Inc 2,5- disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines asallosteric shp2 inhibitors
EP3515916B1 (en) 2016-09-22 2023-06-07 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
TW202500565A (zh) 2016-10-24 2025-01-01 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
CN110730678B (zh) 2017-01-10 2022-07-15 诺华股份有限公司 包含alk抑制剂和shp2抑制剂的药物组合
CA3051054A1 (en) 2017-01-23 2018-07-26 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
CN110446709B (zh) 2017-01-23 2023-09-12 锐新医药公司 作为变构shp2抑制剂的二环化合物
SG11201908820VA (en) 2017-03-23 2019-10-30 Jacobio Pharmaceuticals Co Ltd Novel heterocyclic derivatives useful as shp2 inhibitors
WO2018187423A1 (en) 2017-04-05 2018-10-11 Warp Drive Bio, Inc. Methods and reagents for analyzing protein-protein interfaces
US20200199102A1 (en) 2017-04-05 2020-06-25 Revolution Medicines, Inc. Compounds that participate in cooperative binding and uses thereof
US11591336B2 (en) 2017-05-26 2023-02-28 D. E. Shaw Research, Llc Substituted pyrazolo[3,4-b]pyrazines as SHP2 phosphatase inhibitors
TWI852912B (zh) 2017-09-07 2024-08-21 美商銳新醫藥公司 Shp2抑制劑組合物以及治療癌症的方法
BR112020007058A2 (pt) 2017-10-12 2020-10-06 Revolution Medicines, Inc. compostos de piridina, pirazina, e triazina como inibidores de shp2 alostéricos
BR112020009757A2 (pt) 2017-12-15 2020-11-03 Revolution Medicines, Inc. compostos policíclicos como inibidores alostéricos de shp2
US11498930B2 (en) 2018-02-13 2022-11-15 Blueray Therapeutics (Shanghai) Co., Ltd Pyrimidine-fused cyclic compound, preparation method therefor and application thereof
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
RU2020133727A (ru) 2018-03-21 2022-04-21 Сучжоу Пухе Биофарма Ко., Лтд. Ингибиторы shp2 и их применение
KR20200143417A (ko) 2018-04-10 2020-12-23 레볼루션 메디슨즈, 인크. Shp2 억제제 조성물, 암을 치료하는 방법 및 shp2 돌연변이를 갖는 대상체를 확인하는 방법
EP3788050B1 (en) 2018-05-01 2024-08-28 Revolution Medicines, Inc. C26-linked rapamycin analogs as mtor inhibitors
PL3788049T3 (pl) 2018-05-01 2023-06-19 Revolution Medicines, Inc. Połączone z C40, C28 i C32 analogi rapamycyny jako inhibitory mTOR
AU2019338207B2 (en) 2018-09-10 2025-01-02 Mirati Therapeutics, Inc. Combination therapies
JP7337174B2 (ja) 2018-09-18 2023-09-01 ニカング セラピューティクス， インコーポレイテッド Ｓｒｃホモロジー－２ホスファターゼ阻害剤としての三置換ヘテロアリール誘導体
JP2022508651A (ja) 2018-10-08 2022-01-19 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 癌を処置するためのｓｈｐ２阻害剤組成物および方法
JP7377679B2 (ja) 2018-11-19 2023-11-10 アムジエン・インコーポレーテツド がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法
IL317393A (en) 2018-12-21 2025-02-01 Revolution Medicines Inc Compounds that participate in covalent bonds and their uses
CN121471132A (zh) 2019-11-04 2026-02-06 锐新医药公司 Ras抑制剂

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