CN110785414A - K-Ras调节剂 - Google Patents

K-Ras调节剂 Download PDF

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Publication number
CN110785414A
CN110785414A CN201880037317.9A CN201880037317A CN110785414A CN 110785414 A CN110785414 A CN 110785414A CN 201880037317 A CN201880037317 A CN 201880037317A CN 110785414 A CN110785414 A CN 110785414A
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substituted
unsubstituted
independently
various embodiments
membered
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CN201880037317.9A
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Chinese (zh)
Inventor
F·麦考密克
A·伦斯洛
D·特纳
A·E·玛西雅格
M·迪巴
E·D·武
J·萨韦德拉
V·库马里
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University of California San Diego UCSD
Leidos Biomedical Research Inc
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University of California San Diego UCSD
Leidos Biomedical Research Inc
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Publication of CN110785414A publication Critical patent/CN110785414A/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/24—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to three ring carbon atoms
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
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    • C07C233/13—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Holo Graphy (AREA)
  • Optical Modulation, Optical Deflection, Nonlinear Optics, Optical Demodulation, Optical Logic Elements (AREA)
  • Epoxy Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201880037317.9A 2017-04-20 2018-04-20 K-Ras调节剂 Pending CN110785414A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762487756P 2017-04-20 2017-04-20
US62/487,756 2017-04-20
PCT/US2018/028593 WO2018195439A2 (en) 2017-04-20 2018-04-20 K-ras modulators

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CN110785414A true CN110785414A (zh) 2020-02-11

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US (1) US11358940B2 (https=)
EP (1) EP3612526A2 (https=)
JP (1) JP2020517600A (https=)
KR (1) KR20200011426A (https=)
CN (1) CN110785414A (https=)
AU (1) AU2018255413A1 (https=)
BR (1) BR112019021899A2 (https=)
CA (1) CA3059943A1 (https=)
CL (1) CL2019002968A1 (https=)
EA (1) EA201992497A1 (https=)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112574174A (zh) * 2019-09-27 2021-03-30 恩瑞生物医药科技（上海）有限公司 蛋白降解靶向嵌合体类化合物及其制备方法和医药用途
CN115028678A (zh) * 2022-07-08 2022-09-09 杭州医学院 基于vhl配体诱导bcr-abl蛋白降解的双功能分子及其制备方法和应用

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112017023821A2 (pt) 2015-05-06 2018-07-31 Leidos Biomedical Res Inc moduladores de k-ras
JP7039489B2 (ja) 2016-05-18 2022-03-22 ミラティ セラピューティクス， インコーポレイテッド Ｋｒａｓ ｇ１２ｃ阻害剤
SG11202000230VA (en) 2017-07-11 2020-02-27 Vertex Pharma Carboxamides as modulators of sodium channels
US10647715B2 (en) 2017-11-15 2020-05-12 Mirati Therapeutics, Inc. KRas G12C inhibitors
HRP20230377T1 (hr) 2017-11-15 2023-06-23 Mirati Therapeutics, Inc. Inhibitori mutacije kras g12c
US11932633B2 (en) 2018-05-07 2024-03-19 Mirati Therapeutics, Inc. KRas G12C inhibitors
SMT202500028T1 (it) 2018-09-10 2025-03-12 Mirati Therapeutics Inc Terapie combinate
CA3112043A1 (en) 2018-09-10 2020-03-19 Mirati Therapeutics, Inc. Combination therapies
JP2022500385A (ja) 2018-09-10 2022-01-04 ミラティ セラピューティクス， インコーポレイテッド 組み合わせ療法
WO2020055761A1 (en) 2018-09-10 2020-03-19 Mirati Therapeutics, Inc. Combination therapies
CN113164418A (zh) 2018-12-05 2021-07-23 米拉蒂治疗股份有限公司 组合疗法
WO2020146612A1 (en) 2019-01-10 2020-07-16 Vertex Pharmaceuticals Incorporated Esters and carbamates as modulators of sodium channels
WO2020146613A1 (en) 2019-01-10 2020-07-16 Mirati Therapeutics, Inc. Kras g12c inhibitors
US12441703B2 (en) 2019-01-10 2025-10-14 Vertex Pharmaceuticals Incorporated Carboxamides as modulators of sodium channels
CN120097859A (zh) * 2019-02-19 2025-06-06 加利福尼亚大学董事会 Nurr1受体调节剂
WO2021041671A1 (en) 2019-08-29 2021-03-04 Mirati Therapeutics, Inc. Kras g12d inhibitors
US12122787B2 (en) 2019-09-20 2024-10-22 Shanghai Jemincare Pharmaceuticals Co., Ltd Fused pyridone compound, and preparation method therefor and use thereof
CN114761012B (zh) 2019-09-24 2025-03-21 米拉蒂治疗股份有限公司 组合疗法
CA3164134A1 (en) 2019-12-06 2021-06-10 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofurans as modulators of sodium channels
PH12022551513A1 (en) 2019-12-20 2023-04-24 Mirati Therapeutics Inc Sos1 inhibitors
TW202210633A (zh) 2020-06-05 2022-03-16 法商昂席歐公司 用於治療癌症之dbait分子與kras抑制劑的組合
TW202214574A (zh) * 2020-06-08 2022-04-16 加拿大商愛彼特生物製藥公司 經取代之(呔-1-基甲基)脲類、經取代之n-(呔-1-基甲基)醯胺類及其類似物
IL299131A (en) 2020-06-18 2023-02-01 Revolution Medicines Inc Methods for delaying, preventing and treating acquired resistance to RAS inhibitors
MX2023002248A (es) 2020-09-03 2023-05-16 Revolution Medicines Inc Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2.
WO2022056307A1 (en) 2020-09-11 2022-03-17 Mirati Therapeutics, Inc. Crystalline forms of a kras g12c inhibitor
WO2022132200A1 (en) 2020-12-15 2022-06-23 Mirati Therapeutics, Inc. Azaquinazoline pan-kras inhibitors
EP4262803A4 (en) 2020-12-16 2025-03-12 Mirati Therapeutics, Inc. Tetrahydropyridopyrimidine pan-kras inhibitors
CN116745291A (zh) 2020-12-17 2023-09-12 阿斯利康(瑞典)有限公司 N-(2-(4-氰基噻唑烷-3-基)-2-氧代乙基)-喹啉-4-甲酰胺
JP2024506858A (ja) 2021-02-02 2024-02-15 リミナル・バイオサイエンシーズ・リミテッド Ｇｐｒ８４アンタゴニストおよびその使用
WO2022221451A2 (en) * 2021-04-13 2022-10-20 University Of Virginia Patent Foundation Sulfonyl-triazole compounds useful as ligands and inhibitors of prostaglandin reductase 2
SI4347031T1 (sl) 2021-06-04 2026-01-30 Vertex Pharmaceuticals Incorporated N-(hidroksialkil (hetero)aril) tetrahidrofuran karboksamidi kot modulatorji natrijevih kanalčkov
AR127064A1 (es) 2021-09-15 2023-12-13 Hua Medicine Shanghai Ltd Prodroga de derivados de pirrolidona como activador de glucoquinasa
US20240408064A1 (en) * 2021-10-15 2024-12-12 Genetolead Inc. Ras inhibitors, compositions and methods of use thereof
US20250059187A1 (en) * 2021-12-22 2025-02-20 The Regents Of The University Of California Covalently binding inhibitors of g12s, g12d and/or g12e mutants of k-ras gtpase

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007514003A (ja) * 2003-12-15 2007-05-31 アルミラル プロデスファルマ アーゲー アデノシン受容体アンタゴニストとしての２，６−ビスヘテロアリール−４−アミノピリミジン
JP2010523599A (ja) * 2007-04-05 2010-07-15 シーメンス メディカル ソリューションズ ユーエスエー インコーポレイテッド クリックケミストリーを使用した炭酸脱水酵素−ｉｘのための分子イメージングプローブの開発
WO2016161361A1 (en) * 2015-04-03 2016-10-06 Nantbioscience, Inc. Compositions and methods of targeting mutant k-ras
WO2016179558A1 (en) * 2015-05-06 2016-11-10 The Regents Of The University Of California K-ras modulators

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3131527A1 (de) * 1981-08-08 1983-02-24 Kali-Chemie Pharma Gmbh, 3000 Hannover 1-phenyl-2-aminocarbonylindol-verbindungen sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
JPS61227567A (ja) 1985-04-01 1986-10-09 Eisai Co Ltd １，４−ジヒドロピリジン誘導体
DK626889A (da) 1988-12-16 1990-06-17 Roussel Uclaf Indanderivater, deres fremstilling samt laegemidler med indhold deraf
IL111730A (en) 1993-11-29 1998-12-06 Fujisawa Pharmaceutical Co Piperazine derivatives processes for the preparation thereof and pharmaceutical compositions containing the same
WO1996006078A1 (en) * 1994-08-24 1996-02-29 Pfizer Pharmaceuticals Inc. N-(2-(pyrrolidinyl-1)-1-phenylethyl)acetamides as kappa receptor antagonists
US5475109A (en) 1994-10-17 1995-12-12 Merck & Co., Inc. Dioxobutanoic acid derivatives as inhibitors of influenza endonuclease
US5631251A (en) 1995-06-07 1997-05-20 Merck & Co., Inc. 5-cyclopropyl-1,4 benzodiazepine-2-ones
US6953855B2 (en) 1998-12-11 2005-10-11 Targacept, Inc. 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof
EP1187811B1 (en) 1999-06-04 2007-03-07 AstraZeneca AB Inhibitors of metalloproteinases
KR20020060160A (ko) 1999-08-12 2002-07-16 파마시아 이탈리아 에스.피.에이. 3(5)-아미노-피라졸 유도체, 이의 제조 방법 및항종양제로서의 이의 용도
EP1233013B1 (en) * 1999-11-18 2007-02-28 Ajinomoto Co., Inc. Novel phenylalanine derivatives
WO2003004474A1 (en) * 2001-07-06 2003-01-16 Syngenta Participations Ag Pesticidally active aminoacetonitriles
CA2501611A1 (en) 2002-10-11 2004-04-22 Astrazeneca Ab 1,4-disubstituted piperidine derivatives and their use as 11-betahsd1 inhibitors
BRPI0408284B8 (pt) 2003-03-12 2021-05-25 Kudos Pharm Ltd compostos derivados de ftalazinona, seu uso e composição farmacêutica compreendendo os mesmos
WO2004113274A2 (en) * 2003-05-20 2004-12-29 Bayer Pharmaceuticals Corporation Diaryl ureas with kinase inhibiting activity
US20050119266A1 (en) 2003-10-01 2005-06-02 Yan Shi Pyrrolidine and piperidine derivatives as factor Xa inhibitors
GB0326029D0 (en) 2003-11-07 2003-12-10 Astrazeneca Ab Chemical compounds
JPWO2005047286A1 (ja) 2003-11-13 2007-05-31 小野薬品工業株式会社 スピロ複素環化合物
ES2330451T3 (es) 2004-01-16 2009-12-10 Wyeth Inhibidores a base de sulfonamidas heterociclicas de la produccion de beta-amiloides que contienen un azol.
JP4855485B2 (ja) 2006-02-17 2012-01-18 エフ．ホフマン−ラ ロシュ アーゲー ５ｈｔ２／ｄ３モジュレーターとしてのベンゾイル−ピペリジン誘導体
CA2645652A1 (en) * 2006-03-16 2007-09-27 Renovis, Inc. Bicycloheteroaryl compounds as p2x7 modulators and uses thereof
US20100267779A1 (en) 2007-07-23 2010-10-21 Syndax Pharmaceuticals, Inc. Novel Compounds and Methods of Using Them
SA08290475B1 (ar) 2007-08-02 2013-06-22 Targacept Inc (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه
HUE015568T4 (en) 2008-12-19 2017-10-30 Elanco Tiergesundheit Ag Isoxazoline derivatives and their use as pesticides
MX373926B (es) 2009-05-27 2020-07-10 Ptc Therapeutics Inc Metodos para tratar cancer y estados no neoplasicos.
AR082453A1 (es) 2010-04-21 2012-12-12 Novartis Ag Compuestos de furopiridina, composiciones farmaceuticas que los contienen y usos de los mismos
EP2836482B1 (en) 2012-04-10 2019-12-25 The Regents of The University of California Compositions and methods for treating cancer
EP2698367A1 (en) * 2012-08-14 2014-02-19 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Benzimidazoles for the treatment of cancer
WO2014093230A2 (en) 2012-12-10 2014-06-19 Merck Patent Gmbh Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity
JP6473133B2 (ja) * 2013-03-15 2019-02-20 アラクセス ファーマ エルエルシー Ｋｒａｓｇ１２ｃの共有結合性阻害剤
UY35464A (es) 2013-03-15 2014-10-31 Araxes Pharma Llc Inhibidores covalentes de kras g12c.
US10196369B2 (en) 2013-09-26 2019-02-05 Sanford Burnham Prebys Medical Discovery Institute Spirocyclic EBI2 modulators
HUE064145T2 (hu) * 2016-04-15 2024-03-28 Epizyme Inc Amin-szubsztituált aril- vagy heteroaril vegyületek, mint EHMT1 és EHMT2 inhibitorok

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007514003A (ja) * 2003-12-15 2007-05-31 アルミラル プロデスファルマ アーゲー アデノシン受容体アンタゴニストとしての２，６−ビスヘテロアリール−４−アミノピリミジン
JP2010523599A (ja) * 2007-04-05 2010-07-15 シーメンス メディカル ソリューションズ ユーエスエー インコーポレイテッド クリックケミストリーを使用した炭酸脱水酵素−ｉｘのための分子イメージングプローブの開発
WO2016161361A1 (en) * 2015-04-03 2016-10-06 Nantbioscience, Inc. Compositions and methods of targeting mutant k-ras
WO2016179558A1 (en) * 2015-05-06 2016-11-10 The Regents Of The University Of California K-ras modulators

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GRANT D. GESKE ET AL: "Evaluation of a focused library of N-aryl L-homoserine lactones reveals a new set of potent quorum sensing modulators", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 *
OKAMOTO, K.A,B ET AL: "Reversal of mutant KRAS-mediated apoptosis resistance by concurrent Noxa/Bik induction and Bcl-2/Bcl-xL antagonism in colon cancer cells", 《MOLECULAR CANCER RESEARCH》 *
STN REGISTRY: "STN REGISTRY", 《STN REGISTRY》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112574174A (zh) * 2019-09-27 2021-03-30 恩瑞生物医药科技（上海）有限公司 蛋白降解靶向嵌合体类化合物及其制备方法和医药用途
CN112574174B (zh) * 2019-09-27 2021-12-07 恩瑞生物医药科技（上海）有限公司 蛋白降解靶向嵌合体类化合物及其制备方法和医药用途
CN115028678A (zh) * 2022-07-08 2022-09-09 杭州医学院 基于vhl配体诱导bcr-abl蛋白降解的双功能分子及其制备方法和应用

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