PT3233071T - Método de tratamento ou prevenção de doenças mediadas por ras - Google Patents

Método de tratamento ou prevenção de doenças mediadas por ras

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Publication number
PT3233071T
PT3233071T PT158212183T PT15821218T PT3233071T PT 3233071 T PT3233071 T PT 3233071T PT 158212183 T PT158212183 T PT 158212183T PT 15821218 T PT15821218 T PT 15821218T PT 3233071 T PT3233071 T PT 3233071T
Authority
PT
Portugal
Prior art keywords
treating
mediated diseases
preventing ras
ras
preventing
Prior art date
Application number
PT158212183T
Other languages
English (en)
Inventor
A Piazza Gary
Chen Xi
B Keeton Adam
R Boyd Michael
Original Assignee
Adt Pharmaceuticals Llc
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Filing date
Publication date
Application filed by Adt Pharmaceuticals Llc filed Critical Adt Pharmaceuticals Llc
Publication of PT3233071T publication Critical patent/PT3233071T/pt

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    • C07D317/44Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
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    • A61K31/167Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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    • C07D307/38Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07C2602/08One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9862698B2 (en) * 2014-12-16 2018-01-09 Adt Pharmaceuticals, Inc. Indenyl compounds, pharmaceutical compositions, and medical uses thereof
US20160168108A1 (en) 2014-12-16 2016-06-16 Adt Pharmaceuticals, Inc. Method of treating or preventing ras-mediated diseases
CA3056873A1 (en) * 2017-03-17 2018-09-20 University Of South Alabama Derivatives of sulindac can protect normal cells against oxidative damage
EP3676242B1 (en) 2017-08-31 2024-03-06 Musc Foundation for Research Development Indene derivatives and uses thereof
US11186596B2 (en) 2018-04-26 2021-11-30 Adt Pharmaceuticals, Llc Anticancer indenes, indanes, azaindenes, azaindanes, pharmaceutical compositions and uses
CA3099148A1 (en) 2018-05-10 2019-11-14 The University Of Louisville Research Foundation, Inc. Inhibitors of the ras oncoprotein, methods of making and methods of use thereof
WO2020041364A1 (en) * 2018-08-21 2020-02-27 Board Of Regents, The University Of Texas System Compositions and methods for the treatment of cancer cells by induction of cytotoxic oxidative stress
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
EP4208261A1 (en) 2020-09-03 2023-07-12 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
CN113289020B (zh) * 2021-05-17 2023-04-18 福州大学 蛋白质二硫键异构酶小分子抑制剂及其应用

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL7005270A (pt) 1969-04-29 1970-11-02
US3888902A (en) 1972-10-30 1975-06-10 Merck & Co Inc Cyano-indenyl acetic acids
US3642785A (en) 1969-08-11 1972-02-15 Merck & Co Inc Indenyl-3-aliphatic amines
NL7200058A (pt) 1971-01-21 1972-07-25
ATE40561T1 (de) 1983-07-21 1989-02-15 Troponwerke Gmbh & Co Kg Antiphlogistika enthaltende thermoplastische kunststoffe.
US4656190A (en) 1983-11-14 1987-04-07 Merck & Co., Inc. Indene derivatives and their use as PAF-antagonists
US5093356A (en) 1990-01-16 1992-03-03 Merck Frosst Canada, Inc. Indenyl hydroxamic acids and hydroxy ureas as inhibitors of 5-lipoxygenase
US5401774A (en) 1991-03-08 1995-03-28 University Of Arizona Method for treating patients with precancerous lesions by administering substituted sulfonyl idenyl acetic and propionic acids and esters to patients with lesions sensitive to such compounds
WO1996004266A2 (de) 1994-08-03 1996-02-15 Asta Medica Aktiengesellschaft Indol-, indazol-, pyridopyrrol- und pyridopyrazol-derivate mit antiasthmatischer, antiallergischer, entzündungshemmender und immunmodulierender wirkung
US6063818A (en) 1996-06-13 2000-05-16 Cell Pathways Inc. Substituted benzylidene indenyl formamides, acetamides and propionamides
US5965619A (en) 1996-06-13 1999-10-12 Cell Pathways Inc. Method for treating patients having precancerous lesions with substituted indene derivatives
US6121321A (en) 1996-06-13 2000-09-19 Cell Pathways, Inc. Substituted methoxy benzylidene indenyl acetic and propionic acids for treating patients with precancerous lesions
US6071934A (en) 1997-03-25 2000-06-06 Cell Pathways, Inc. Indenyl hydroxamic acids, (hydroxy) ureas and urethanes for treating patients with precancerous lesions
HUP9903620A3 (en) 1997-06-12 2001-03-28 Univ Arizona Tucson Pharmaceutical compositions containing substituted benzylidene indenyl formamides, acetamide and propionamide derivatives and use of these compounds
TR200001687T2 (tr) 1997-12-12 2000-10-23 Cell Pathways, Inc. Neopleasyo için N-benzil-3-indenilasetamid türevleri.
US6028116A (en) 1998-04-03 2000-02-22 Cell Pathways, Inc. Substituted condensation products of 1H-indenyl-hydroxyalkanes with aldehydes for neoplasia
MXPA02006312A (es) 1999-12-23 2004-06-21 Nitromed Inc Inhibidores de ciclooxigenasa-2 nitrosilatados y nitrosados, composiciones y metodos para utilizarse.
EP1157027B1 (en) 1999-12-28 2007-09-19 Basell Polyolefine GmbH Heterocyclic metallocene compounds and use thereof in catalyst systems for producing olefin polymers
JP2004510762A (ja) 2000-10-02 2004-04-08 メルク エンド カムパニー インコーポレーテッド プレニル−蛋白質トランスフェラーゼの阻害剤
US20030176316A1 (en) 2001-08-24 2003-09-18 Whitehead Clark M. Methods for treatment of rheumatoid arthritis
DE10163426A1 (de) * 2001-12-21 2003-07-03 Max Planck Gesellschaft Pharmakologisch wirksame Inden-Derivate
US20030194750A1 (en) 2002-04-05 2003-10-16 Han Li Methods for treatment of diseases where GSK 3-beta is desired, and methods to identify compounds usefule for that
US6538029B1 (en) 2002-05-29 2003-03-25 Cell Pathways Methods for treatment of renal cell carcinoma
EP1539679A4 (en) 2002-06-28 2007-07-04 Nitromed Inc OXIM- AND / OR HYDRAZO-CONTAINING, NITROSED AND / OR NITROSYLATED CYCLOOXIGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND USE METHODS
EP1744747A4 (en) 2004-04-26 2009-12-02 Univ Vanderbilt INDIC ACID AND INDULECTIC ACID DERIVATIVES AS THERAPEUTIC ACTIVITIES WITH REDUCED GASTROINTESTINAL TOXICITY
WO2006124874A2 (en) 2005-05-12 2006-11-23 Kalypsys, Inc. Inhibitors of b-raf kinase
GB0525143D0 (en) 2005-12-09 2006-01-18 Novartis Ag Organic compounds
EA016323B1 (ru) 2006-01-04 2012-04-30 Саутерн Рисерч Инститьют Производные сулиндака, их применение и получение
WO2008012603A1 (en) 2006-07-26 2008-01-31 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of diflunisal and related compounds with very fast skin penetration rate
AU2016219617B2 (en) 2006-07-09 2018-05-17 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of aspirin
WO2008044095A1 (en) 2006-10-11 2008-04-17 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of oxicams and related compounds with very high skin penetration rate
JP5759672B2 (ja) 2006-07-09 2015-08-05 テックフィールズ バイオケム カンパニー リミテッド アスピリンの正荷電水溶性プロドラッグ
AU2013206215C9 (en) 2006-07-09 2018-03-08 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of aspirin
US20090221703A1 (en) 2006-07-09 2009-09-03 Chongxi Yu High penetration composition and uses thereof
AU2013231152B2 (en) 2006-07-18 2016-06-09 Techfields Biochem Co. Ltd Positively charged water-soluble pro-drugs of ibuprofen
DK2041068T3 (en) 2006-07-18 2017-02-27 Techfields Biochem Co Ltd POSITIVELY CHARGED, WATER SOLUBLE PRODRUGS OF IBUPROFEN WITH VERY FAST SKIN PENETRATION SPEED
PL2046727T3 (pl) 2006-07-25 2014-08-29 Techfields Biochem Co Ltd Dodatnio naładowane rozpuszczalne w wodzie proleki diklofenaku o bardzo szybkim stopniu przenikania przez skórę
CN101500984A (zh) 2006-07-27 2009-08-05 于崇曦 具有快速皮肤穿透速度的带正电荷的水溶性酮洛芬及相关化合物的前药
EA018724B1 (ru) 2006-08-07 2013-10-30 Айронвуд Фармасьютикалз, Инк. Соединения индола
PL2049482T3 (pl) 2006-08-08 2016-04-29 Techfields Biochem Co Ltd Dodatnio naładowane rozpuszczalne w wodzie proleki kwasów arylo- i heteroarylooctowych o bardzo dużej szybkości przenikania przez skórę
CA2660814C (en) 2006-08-15 2017-07-18 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of aryl- and heteroarylpropionic acids with very fast skin penetration rate
AU2013206218B2 (en) 2006-08-15 2016-06-30 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of aryl- and heteroarylpropionic acids with very fast skin penetration rate
PL2084132T3 (pl) 2006-09-03 2019-03-29 Techfields Biochem Co. Ltd Dodatnio naładowane rozpuszczalne w wodzie proleki z kwasów n-arylantranilowych z bardzo szybką penetracją skóry
AU2014201024B2 (en) 2006-09-03 2016-05-05 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of acetaminophen and related compounds with very fast skin penetration rate
EP2061749B1 (en) 2006-09-03 2018-02-21 Techfields Biochem Co. Ltd Positively charged water-soluble prodrugs of acetaminophen and related compounds with very fast skin penetration rate
AU2007354632B2 (en) 2007-06-04 2014-06-26 Techfields Inc Pro-drugs of NSAIAs with very high skin and membranes penetration rates and their new medicinal uses
EA201201031A1 (ru) 2010-01-25 2013-02-28 Энанта Фармасьютиклз, Инк. Ингибиторы вируса гепатита с
BR112013024525A2 (pt) 2011-04-01 2017-04-18 Southern Res Inst compostos, composição farmacêutica e métodos para tratar condição pré-cancerosa ou câncer em mamífero, pacientes com doença inflamatória crônica ou doença neurodegenerativa e para preparar compostos e usos de compostos e de composição farmacêutica
EP2897621A4 (en) 2012-09-21 2016-08-10 Basil Rigas COMPOUNDS AND COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF INFLAMMATORY DISEASES, PAIN AND FEVER, SKIN DISEASES, CANCER AND PRECULTURAL INJURIES
CA2908383A1 (en) 2013-04-09 2014-10-16 Materia, Inc. Preparation of surfactants via cross-metathesis
WO2015126462A1 (en) 2014-02-19 2015-08-27 Materia, Inc. Preparation of surfactants via cross-metathesis
US20170342021A1 (en) 2014-12-16 2017-11-30 Adt Pharmaceuticals, Inc. Ras-inhibiting indenyl acetamide compounds, compositions, and uses
US9862698B2 (en) 2014-12-16 2018-01-09 Adt Pharmaceuticals, Inc. Indenyl compounds, pharmaceutical compositions, and medical uses thereof
US20160168108A1 (en) 2014-12-16 2016-06-16 Adt Pharmaceuticals, Inc. Method of treating or preventing ras-mediated diseases
WO2017106520A1 (en) 2015-12-16 2017-06-22 Adt Pharmaceuticals, Inc. Compounds, compositions and methods of treating cancer
US11186596B2 (en) 2018-04-26 2021-11-30 Adt Pharmaceuticals, Llc Anticancer indenes, indanes, azaindenes, azaindanes, pharmaceutical compositions and uses

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