HRP950033A2 - Tricyclic compounds capable of inhibiting tryosine kinases of the epidermal growth factor receptor family - Google Patents
Tricyclic compounds capable of inhibiting tryosine kinases of the epidermal growth factor receptor family Download PDFInfo
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- HRP950033A2 HRP950033A2 HR08/358,352A HRP950033A HRP950033A2 HR P950033 A2 HRP950033 A2 HR P950033A2 HR P950033 A HRP950033 A HR P950033A HR P950033 A2 HRP950033 A2 HR P950033A2
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- carbon atoms
- nitrogen
- represent
- carbon
- lower alkyl
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- 150000001875 compounds Chemical class 0.000 title claims description 66
- 102000001301 EGF receptor Human genes 0.000 title claims description 23
- 108060006698 EGF receptor Proteins 0.000 title claims description 21
- 230000002401 inhibitory effect Effects 0.000 title claims description 4
- 108091000080 Phosphotransferase Proteins 0.000 title description 3
- 102000020233 phosphotransferase Human genes 0.000 title description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 494
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 455
- 229910052757 nitrogen Inorganic materials 0.000 claims description 273
- 125000000217 alkyl group Chemical group 0.000 claims description 188
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 173
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- 239000001257 hydrogen Substances 0.000 claims description 159
- 229910052739 hydrogen Inorganic materials 0.000 claims description 159
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 129
- 229910052717 sulfur Inorganic materials 0.000 claims description 114
- 238000000034 method Methods 0.000 claims description 111
- 229910052760 oxygen Inorganic materials 0.000 claims description 109
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 102
- -1 -O-C(O)-R) Chemical group 0.000 claims description 97
- 235000001508 sulfur Nutrition 0.000 claims description 92
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 91
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 90
- 239000011593 sulfur Substances 0.000 claims description 88
- 239000000203 mixture Substances 0.000 claims description 81
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 76
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- 125000004663 dialkyl amino group Chemical group 0.000 claims description 44
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- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 229940116977 epidermal growth factor Drugs 0.000 claims description 34
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 33
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D491/12—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 three hetero rings
- C07D491/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
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- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Dermatology (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 Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/358,352 US5679683A (en) | 1994-01-25 | 1994-12-23 | Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
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AU (1) | AU686339B2 (cs) |
BG (1) | BG63432B1 (cs) |
CZ (1) | CZ197196A3 (cs) |
FI (1) | FI114098B (cs) |
GE (1) | GEP20002330B (cs) |
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IL (1) | IL112248A0 (cs) |
MD (1) | MD1616G2 (cs) |
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PL (1) | PL315632A1 (cs) |
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Families Citing this family (381)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2109796T3 (es) * | 1994-05-03 | 1998-01-16 | Ciba Geigy Ag | Derivados de pirrolopirimidilo con efecto antiproliferante. |
US5476851A (en) * | 1994-09-08 | 1995-12-19 | Rhone-Poulenc Rorer Pharmaceuticals, Inc. | Pyrazolo[3,4-g]quinoxaline compounds which inhibit PDGF receptor protein tyrosine kinase |
TW321649B (cs) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
GB9424233D0 (en) * | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
WO1996029331A1 (de) * | 1995-03-20 | 1996-09-26 | Dr. Karl Thomae Gmbh | Imidazochinazoline, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
DE69609602T2 (de) * | 1995-04-03 | 2001-04-12 | Novartis Ag | Pyrazolderivate und verfahren zu deren herstellung |
GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
DE69613367T2 (de) * | 1995-04-27 | 2002-04-18 | Astrazeneca Ab | Chinazolin derivate |
GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
GB9508537D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
GB9508535D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
CZ1598A3 (cs) * | 1995-07-06 | 1998-04-15 | Novartis Ag | Pyrrolopyrimidiny a způsoby jejich přípravy |
GB9520822D0 (en) * | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
BR9707495A (pt) | 1996-02-13 | 1999-07-27 | Zeneca Ltd | Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente |
GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9603097D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline compounds |
KR100489174B1 (ko) | 1996-03-05 | 2005-09-30 | 제네카-파마 소시에떼아노님 | 4-아닐리노퀴나졸린유도체 |
CN100503580C (zh) | 1996-04-12 | 2009-06-24 | 沃尼尔·朗伯公司 | 酪氨酸激酶的不可逆抑制剂 |
GB9607729D0 (en) * | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
CA2258548C (en) * | 1996-06-24 | 2005-07-26 | Pfizer Inc. | Phenylamino-substituted tricyclic derivatives for treatment of hyperproliferative diseases |
WO1998007726A1 (en) | 1996-08-23 | 1998-02-26 | Novartis Ag | Substituted pyrrolopyrimidines and processes for their preparation |
US6127541A (en) * | 1996-08-30 | 2000-10-03 | Kyowa Hakko Kogyo Co., Ltd. | Imidazoquinazoline derivatives |
AU720135B2 (en) | 1996-10-02 | 2000-05-25 | Novartis Ag | Pyrimidine derivatives and processes for the preparation thereof |
US6225318B1 (en) | 1996-10-17 | 2001-05-01 | Pfizer Inc | 4-aminoquinazolone derivatives |
US6057329A (en) * | 1996-12-23 | 2000-05-02 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives |
US6002008A (en) * | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
ZA986732B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
US6251912B1 (en) | 1997-08-01 | 2001-06-26 | American Cyanamid Company | Substituted quinazoline derivatives |
US6323209B1 (en) | 1997-11-06 | 2001-11-27 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
EP2011499A3 (en) | 1998-06-02 | 2010-10-20 | OSI Pharmaceuticals, Inc. | Pyrrolo[2,3d]Pyrimidine compositions and their use |
US6878716B1 (en) | 1998-06-02 | 2005-04-12 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptor and uses thereof |
US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
JP4537582B2 (ja) | 1998-09-29 | 2010-09-01 | アメリカン・サイアナミド・カンパニー | プロテインチロシンキナーゼインヒビターとしての置換3−シアノキノリン |
KR20010099877A (ko) * | 1998-12-22 | 2001-11-09 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | 배합물 화학요법 |
US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
DE60017446T2 (de) * | 1999-11-05 | 2006-03-02 | Smithkline Beecham P.L.C., Brentford | Isochinolin- und Chinazolinderivate mit kombinierter 5-HT1A-, 5-HT1B- und 5-HT1D- Rezeptoraffinität |
AU769222B2 (en) | 1999-11-05 | 2004-01-22 | Genzyme Corporation | Quinazoline derivatives as VEGF inhibitors |
UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
US6680322B2 (en) | 1999-12-02 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
US7160890B2 (en) | 1999-12-02 | 2007-01-09 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
US6664252B2 (en) | 1999-12-02 | 2003-12-16 | Osi Pharmaceuticals, Inc. | 4-aminopyrrolo[2,3-d]pyrimidine compounds specific to adenosine A2a receptor and uses thereof |
US6638929B2 (en) | 1999-12-29 | 2003-10-28 | Wyeth | Tricyclic protein kinase inhibitors |
US6838484B2 (en) | 2000-08-24 | 2005-01-04 | University Of Tennessee Research Foundation | Formulations comprising selective androgen receptor modulators |
US6680324B2 (en) | 2000-12-01 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
JP2004523509A (ja) | 2000-12-29 | 2004-08-05 | ワイス | ベンゾ〔g〕キノリン−3−カルボニトリルの置換体およびベンゾ〔g〕キナゾリンの置換体の位置選択的調製方法 |
MX349009B (es) | 2001-01-05 | 2017-07-06 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina. |
AU2002345792A1 (en) | 2001-06-21 | 2003-01-08 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
EP1442039A1 (en) * | 2001-10-31 | 2004-08-04 | Bayer HealthCare AG | Pyrimido (4,5-b) indole derivatives |
AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
AU2002360436A1 (en) | 2001-11-30 | 2003-06-17 | Osi Pharmaceuticals, Inc. | 2-aryl pyrrologpyrimidines for a1 and a3 receptors |
JP2003183283A (ja) * | 2001-12-18 | 2003-07-03 | Takeda Chem Ind Ltd | 縮合インドール化合物、その製造法および用途 |
EP1466907B1 (en) * | 2001-12-19 | 2011-08-10 | Ube Industries, Ltd. | Process for producing quinazolin-4-one and derivative thereof |
CA2471059C (en) | 2001-12-20 | 2011-04-26 | Osi Pharmaceuticals, Inc. | Pyrimidine a2b selective antagonist compounds, their synthesis and use |
ES2328029T3 (es) | 2002-01-28 | 2009-11-06 | Ube Industries, Ltd. | Proceso para producir un derivado de quinazolin-4-ona. |
US7078409B2 (en) | 2002-03-28 | 2006-07-18 | Beta Pharma, Inc. | Fused quinazoline derivatives useful as tyrosine kinase inhibitors |
UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
AU2003262008A1 (en) * | 2002-11-18 | 2004-06-15 | Akimitsu Okamoto | Polynucleotide derivative and use thereof |
BR0317548A (pt) | 2002-12-19 | 2005-11-22 | Pfizer | Compostos de indazole e composições farmacêuticas para a inibição de proteìnas-cinases e métodos para o seu uso |
DK2476667T3 (da) | 2003-02-26 | 2014-09-15 | Sugen Inc | Aminoheteroaryl-forbindelser som proteinkinase-inhibitorer |
EP1637523A4 (en) * | 2003-06-18 | 2009-01-07 | Ube Industries | PROCESS FOR PRODUCING A PYRIMIDIN-4-ONE COMPOUND |
GB0315966D0 (en) * | 2003-07-08 | 2003-08-13 | Cyclacel Ltd | Compounds |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
ES2314444T3 (es) | 2003-08-29 | 2009-03-16 | Pfizer Inc. | Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos. |
AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
US7291733B2 (en) | 2003-10-10 | 2007-11-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted tricyclic heterocycles and their uses |
ES2305887T3 (es) | 2003-12-18 | 2008-11-01 | Janssen Pharmaceutica Nv | Derivados de pirido y pirimidopirimidinas como agentes antiproliferativos. |
CA2551508C (en) | 2003-12-23 | 2011-08-09 | Pfizer Inc. | Novel quinoline derivatives |
US7388014B2 (en) * | 2004-02-19 | 2008-06-17 | Rexahn Pharmaceuticals, Inc. | Quinazoline derivatives and therapeutic use thereof |
GEP20105024B (en) | 2004-06-02 | 2010-06-25 | Takeda Pharmaceuticals Co | Fused heterocyclic compound |
KR20080019733A (ko) | 2004-07-16 | 2008-03-04 | 화이자 프로덕츠 인코포레이티드 | 항-아이지에프-1알 항체를 사용하는 비-혈액학적악성종양에 대한 조합 치료 |
US8207172B2 (en) * | 2004-08-20 | 2012-06-26 | Bayer Intellectual Property Gmbh | Pyrimidinothienoindazoles useful for the treatment of hyperproliferative disorders |
UA87153C2 (ru) | 2004-08-26 | 2009-06-25 | Пфайзер Инк. | Энантиомерно чистые аминогетероарильные соединения как ингибиторы протеинкиназы |
JP5070059B2 (ja) | 2004-10-27 | 2012-11-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 新規ピリミドチエノインダゾール類 |
NI200700147A (es) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina inhibidores de cinasas dirigidos a multip |
US20090155247A1 (en) * | 2005-02-18 | 2009-06-18 | Ashkenazi Avi J | Methods of Using Death Receptor Agonists and EGFR Inhibitors |
US20060188498A1 (en) * | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
EP2444099A1 (en) | 2005-03-31 | 2012-04-25 | Agensys, Inc. | Antibodies and related molecules that bind to 161P2F10B proteins |
EP2444419A1 (en) | 2005-04-26 | 2012-04-25 | Pfizer Inc. | P-Cadherin antibodies |
UA94060C2 (ru) | 2005-09-07 | 2011-04-11 | Эмджен Фримонт Инк. | Моноклональное антитело, которое специфически связывает alk-1 |
CA2623125A1 (en) | 2005-09-20 | 2007-03-29 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
CA2651898A1 (en) * | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions |
CN101490046A (zh) | 2006-05-09 | 2009-07-22 | 辉瑞产品公司 | 环烷基氨基酸衍生物及其药物组合物 |
NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
DE102006029573A1 (de) * | 2006-06-22 | 2007-12-27 | Bayer Schering Pharma Ag | Neue Quinazoline als Kinase-Inhibitoren |
ES2530438T3 (es) | 2006-09-12 | 2015-03-02 | Genentech Inc | Procedimientos y composiciones para el diagnóstico y tratamiento del cáncer de pulmón utilizando el gen de KIT o KDR como marcador genético |
SG176461A1 (en) | 2006-11-06 | 2011-12-29 | Supergen Inc | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
EP2851091B1 (en) | 2007-04-13 | 2017-12-27 | Dana-Farber Cancer Institute, Inc. | Methods for treating cancer resistant to ERBB therapeutics |
WO2008147687A1 (en) * | 2007-05-21 | 2008-12-04 | Mayo Foundation For Medical Education And Research | Treating pancreatitis |
US8618121B2 (en) | 2007-07-02 | 2013-12-31 | Cancer Research Technology Limited | 9H-pyrimido[4,5-B]indoles, 9H-pyrido[4',3':4,5]pyrrolo[2,3-D]pyridines, and 9H 1,3,6,9 tetraaza-fluorenes as CHK1 kinase function inhibitors |
TWI595005B (zh) | 2007-08-21 | 2017-08-11 | 安健股份有限公司 | 人類c-fms抗原結合蛋白質 |
US7960400B2 (en) | 2007-08-27 | 2011-06-14 | Duquesne University Of The Holy Ghost | Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof |
US7982035B2 (en) | 2007-08-27 | 2011-07-19 | Duquesne University Of The Holy Spirit | Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof |
DK2185574T3 (da) | 2007-09-07 | 2013-08-05 | Agensys Inc | Antistoffer og relaterede molekyler, der bindes til 24P4C12-proteiner |
US20110053991A1 (en) * | 2007-11-19 | 2011-03-03 | Gore Lia | Treatment of Histone Deacetylase Mediated Disorders |
TW200930375A (en) * | 2007-12-21 | 2009-07-16 | Exelixis Inc | Benzofuropyrimidinones |
TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至her2結構域ii之抗體及其酸性變異體的組合物 |
HUE028347T2 (en) | 2008-06-10 | 2016-12-28 | Abbvie Inc | Tricyclic compounds |
CA2737597C (en) | 2008-10-16 | 2017-03-14 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof |
MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
US20100204221A1 (en) | 2009-02-09 | 2010-08-12 | Hariprasad Vankayalapati | Pyrrolopyrimidinyl axl kinase inhibitors |
JP2012518657A (ja) | 2009-02-25 | 2012-08-16 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 併用抗癌治療 |
US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
WO2010099363A1 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
US20120064072A1 (en) | 2009-03-18 | 2012-03-15 | Maryland Franklin | Combination Cancer Therapy Comprising Administration of an EGFR Inhibitor and an IGF-1R Inhibitor |
KR20150036824A (ko) | 2009-03-20 | 2015-04-07 | 제넨테크, 인크. | 이중특이적 항-her 항체 |
WO2011027249A2 (en) | 2009-09-01 | 2011-03-10 | Pfizer Inc. | Benzimidazole derivatives |
EP2473487B1 (en) | 2009-09-03 | 2016-10-26 | Bristol-Myers Squibb Company | Quinazolines as potassium ion channel inhibitors |
CN102612374A (zh) | 2009-11-12 | 2012-07-25 | 霍夫曼-拉罗奇有限公司 | 提升树突棘密度的方法 |
WO2011058164A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
KR101785257B1 (ko) * | 2009-12-01 | 2017-10-16 | 애브비 인코포레이티드 | 신규한 트리사이클릭 화합물 |
EP2523957A1 (en) | 2010-01-12 | 2012-11-21 | F. Hoffmann-La Roche AG | Tricyclic heterocyclic compounds, compositions and methods of use thereof |
RU2570198C2 (ru) | 2010-02-12 | 2015-12-10 | Пфайзер Инк. | СОЛИ И ПОЛИМОРФЫ 8-ФТОР-2-{4-[(МЕТИЛАМИНО)МЕТИЛ]ФЕНИЛ}-1,3,4,5-ТЕТРАГИДРО-6Н-АЗЕПИНО[5,4,3-cd]ИНДОЛ-6-ОНА |
SI2536748T1 (sl) | 2010-02-18 | 2014-12-31 | Genentech, Inc. | Nevrogulinski antagonisti in njihova uporaba pri zdravljenju raka |
AU2011223655A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
AU2011223643A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
EP2547338A2 (en) | 2010-03-17 | 2013-01-23 | F. Hoffmann-La Roche AG | Imidazopyridine compounds, compositions and methods of use |
RU2012148699A (ru) | 2010-04-16 | 2014-05-27 | Дженентек, Инк. | Foxo3a как прогностический биомаркер для эффективности ингибитора пути киназы pi3k/акт |
ES2695899T3 (es) | 2010-06-16 | 2019-01-11 | Univ Pittsburgh Commonwealth Sys Higher Education | Anticuerpos contra endoplasmina y su uso |
RU2013114360A (ru) | 2010-08-31 | 2014-10-10 | Дженентек, Инк. | Биомаркеры и способы лечения |
EP2616072A1 (en) | 2010-09-15 | 2013-07-24 | F.Hoffmann-La Roche Ag | Azabenzothiazole compounds, compositions and methods of use |
CA2813162C (en) | 2010-10-20 | 2015-06-16 | Pfizer Inc. | Pyridine-2- derivatives as smoothened receptor modulators |
MX2013005445A (es) | 2010-11-19 | 2013-07-29 | Hoffmann La Roche | Pirazolopiridinas y el uso de pirazolopiridinas como inhibidores de tirosina cinasa 2 (tyk2). |
EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
ES2740399T3 (es) | 2011-03-09 | 2020-02-05 | Richard G Pestell | Líneas de células de cáncer de próstata, firmas genéticas y usos de estas |
WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
WO2012142164A1 (en) | 2011-04-12 | 2012-10-18 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii |
US20140178368A1 (en) | 2011-04-19 | 2014-06-26 | Leslie Lynne SHARP | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 癌薬剤発見、診断、および治療におけるemt遺伝子シグネチャーの使用 |
WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
US9416132B2 (en) | 2011-07-21 | 2016-08-16 | Tolero Pharmaceuticals, Inc. | Substituted imidazo[1,2-b]pyridazines as protein kinase inhibitors |
CN103889976A (zh) | 2011-08-12 | 2014-06-25 | 弗·哈夫曼-拉罗切有限公司 | 吲唑化合物、组合物及使用方法 |
US20140363438A1 (en) | 2011-08-17 | 2014-12-11 | Genentech, Inc. | Neuregulin antibodies and uses thereof |
CN103797002B (zh) * | 2011-08-19 | 2017-02-22 | 迪亚克森海特公司 | Dyrk1抑制剂及其用途 |
JP6297490B2 (ja) | 2011-08-31 | 2018-03-20 | ジェネンテック, インコーポレイテッド | 診断マーカー |
JP2014526538A (ja) | 2011-09-20 | 2014-10-06 | エフ.ホフマン−ラ ロシュ アーゲー | イミダゾピリジン化合物、組成物及び使用方法 |
UA110259C2 (uk) | 2011-09-22 | 2015-12-10 | Пфайзер Інк. | Похідні піролопіримідину і пурину |
AU2012321248A1 (en) | 2011-09-30 | 2014-04-24 | Genentech, Inc. | Diagnostic methylation markers of epithelial or mesenchymal phenotype and response to EGFR kinase inhibitor in tumours or tumour cells |
US9783613B2 (en) | 2011-10-04 | 2017-10-10 | Igem Therapeutics Limited | IgE anti-HMW-MAA antibody |
RU2014114015A (ru) | 2011-11-08 | 2015-12-20 | Пфайзер Инк. | Способы лечения воспалительных расстройств с использованием антител против m-csf |
BR112014010938A2 (pt) | 2011-11-09 | 2017-05-16 | Cancer Res Tech Ltd | compostos de 5-(piridin-2-il-amino)-pirazina-2-carbonitrila e seu uso terapêutico |
MX2014006529A (es) | 2011-11-30 | 2014-11-25 | Genentech Inc | Mutaciones de erbb3 en cancer. |
TR201909582T4 (tr) | 2012-01-27 | 2019-07-22 | Univ Montreal | Pirimido[4,5-b]indol türevleri ve hematopoetik kök hücrelerinin ekspresyonunda bunlarin kullanimi. |
AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
EP2831115A1 (en) | 2012-03-27 | 2015-02-04 | F. Hoffmann-La Roche AG | Diagnosis and treatments relating to her3 inhibitors |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
US9453836B2 (en) | 2012-05-14 | 2016-09-27 | Richard G. Pestell | Use of modulators of CCR5 in the treatment of cancer and cancer metastasis |
KR102090792B1 (ko) | 2012-05-15 | 2020-03-18 | 캔써 리서치 테크놀로지 리미티드 | 5-[[4-[[모르폴린-2-일]메틸아미노]-5-(트리플루오로메틸)-2-피리딜]아미노]피라진-2-카보니트릴 및 그의 치료적 용도 |
WO2013174743A1 (en) | 2012-05-21 | 2013-11-28 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyrimidines |
WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
DK2909181T3 (da) | 2012-10-16 | 2017-11-20 | Tolero Pharmaceuticals Inc | PKM2-modulatorer og fremgangsmåder til anvendelse deraf |
CN102875558A (zh) * | 2012-11-05 | 2013-01-16 | 贵州大学 | 2-氯-4-取代-8-硝基苯并呋喃[3,2-d]嘧啶类化合物及其制备方法和用途 |
US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
KR20150118159A (ko) | 2013-02-22 | 2015-10-21 | 에프. 호프만-라 로슈 아게 | 암의 치료 방법 및 약물 내성의 예방 방법 |
JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス,インク. | 癌治療 |
WO2014138364A2 (en) | 2013-03-06 | 2014-09-12 | Genentech, Inc. | Methods of treating and preventing cancer drug resistance |
MX2015011898A (es) | 2013-03-13 | 2016-05-05 | Genentech Inc | Compuestos de pirazolo y usos de los mismos. |
MX2015010854A (es) | 2013-03-14 | 2016-07-20 | Genentech Inc | Combinaciones de un compuesto inhibidor de mek con un compuesto inhibidor de her3/egfr y metodos de uso. |
WO2014153030A2 (en) | 2013-03-14 | 2014-09-25 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
MX2015012062A (es) | 2013-03-14 | 2016-05-05 | Tolero Pharmaceuticals Inc | Inhibidores de jak2 y alk2 y metodos para su uso. |
RU2015143437A (ru) | 2013-03-15 | 2017-04-27 | Дженентек, Инк. | Способы лечения рака и предотвращения устойчивости к лекарственным препаратам для лечения рака |
WO2014147246A1 (en) | 2013-03-21 | 2014-09-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
WO2015035062A1 (en) | 2013-09-05 | 2015-03-12 | Genentech, Inc. | Antiproliferative compounds |
WO2015035410A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutic, Inc. | Cancer therapy |
AR097894A1 (es) | 2013-10-03 | 2016-04-20 | Hoffmann La Roche | Inhibidores terapéuticos de cdk8 o uso de los mismos |
EA032196B1 (ru) * | 2013-10-03 | 2019-04-30 | Кура Онколоджи, Инк. | Ингибиторы erk и способы применения |
WO2015051302A1 (en) | 2013-10-04 | 2015-04-09 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
CN105744954B (zh) | 2013-10-18 | 2021-03-05 | 豪夫迈·罗氏有限公司 | 抗rspo2和/或抗rspo3抗体及其用途 |
UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
US20150190506A1 (en) | 2013-12-17 | 2015-07-09 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
SG11201604995YA (en) | 2013-12-17 | 2016-07-28 | Genentech Inc | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
CN107002119A (zh) | 2014-03-24 | 2017-08-01 | 豪夫迈·罗氏有限公司 | 使用c‑met拮抗剂的癌症治疗及前者与hgf表达的关联 |
LT3126394T (lt) | 2014-03-31 | 2020-01-27 | F. Hoffmann-La Roche Ag | Antikūnai prieš ox40 ir jų naudojimo būdai |
MA39817A (fr) | 2014-03-31 | 2017-02-08 | Hoffmann La Roche | Thérapie combinatoires comprenant des agents anti-angiogenèse et des agonistes se liant à ox40 |
US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
CR20160497A (es) | 2014-04-30 | 2016-12-20 | Pfizer | Derivados de diheterociclo enlazado a cicloalquilo |
WO2015195684A2 (en) | 2014-06-16 | 2015-12-23 | University Of Rochester | Small molecule anti-scarring agents |
WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
ES2925224T3 (es) | 2014-07-31 | 2022-10-14 | Us Gov Health & Human Services | Anticuerpos monoclonales humanos contra EphA4 y su uso |
EP3189046B1 (en) | 2014-09-05 | 2020-08-26 | Genentech, Inc. | Therapeutic compounds and uses thereof |
CN107073125A (zh) | 2014-09-19 | 2017-08-18 | 基因泰克公司 | Cbp/ep300和bet抑制剂用于治疗癌症的用途 |
EP3204379B1 (en) | 2014-10-10 | 2019-03-06 | Genentech, Inc. | Pyrrolidine amide compounds as histone demethylase inhibitors |
EP3215637B1 (en) | 2014-11-03 | 2019-07-03 | F. Hoffmann-La Roche AG | Methods and biomarkers for predicting efficacy and valuation of an ox40 agonist treatment |
MX2017005750A (es) | 2014-11-03 | 2017-12-15 | Genentech Inc | Ensayos para detectar subgrupos inmunes de células t y sus métodos de uso. |
RU2017119428A (ru) | 2014-11-06 | 2018-12-06 | Дженентек, Инк. | Комбинированная терапия, включающая применение агонистов, связывающихся с ох40, и ингибиторов tigit |
MA40940A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
CN107108613B (zh) | 2014-11-10 | 2020-02-25 | 基因泰克公司 | 布罗莫结构域抑制剂及其用途 |
MA40943A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
KR20170096112A (ko) | 2014-11-17 | 2017-08-23 | 제넨테크, 인크. | Ox40 결합 효능제 및 pd-1 축 결합 길항제를 포함하는 조합 요법 |
EP3224258B1 (en) | 2014-11-27 | 2019-08-14 | Genentech, Inc. | 4,5,6,7-tetrahydro-1h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
EP3233829B1 (en) | 2014-12-18 | 2019-08-14 | Pfizer Inc | Pyrimidine and triazine derivatives and their use as axl inhibitors |
KR20170094165A (ko) | 2014-12-23 | 2017-08-17 | 제넨테크, 인크. | 화학요법-내성 암을 치료 및 진단하는 조성물 및 방법 |
CA2969830A1 (en) | 2014-12-24 | 2016-06-30 | Genentech, Inc. | Therapeutic, diagnostic and prognostic methods for cancer of the bladder |
CN107208138A (zh) | 2014-12-30 | 2017-09-26 | 豪夫迈·罗氏有限公司 | 用于癌症预后和治疗的方法和组合物 |
CN107406429B (zh) | 2015-01-09 | 2021-07-06 | 基因泰克公司 | 哒嗪酮衍生物及其在治疗癌症中的用途 |
JP6855379B2 (ja) | 2015-01-09 | 2021-04-07 | ジェネンテック, インコーポレイテッド | 癌の処置のためのヒストンデメチラーゼkdm2bのインヒビターとしての(ピペリジン−3−イル)(ナフタレン−2−イル)メタノン誘導体および関連化合物 |
JP6889661B2 (ja) | 2015-01-09 | 2021-06-18 | ジェネンテック, インコーポレイテッド | 4,5−ジヒドロイミダゾール誘導体およびヒストンジメチラーゼ(kdm2b)インヒビターとしてのその使用 |
EP3250571B1 (en) | 2015-01-29 | 2022-11-30 | Genentech, Inc. | Therapeutic compounds and uses thereof |
JP6636031B2 (ja) | 2015-01-30 | 2020-01-29 | ジェネンテック, インコーポレイテッド | 治療用化合物およびその使用 |
MA41598A (fr) | 2015-02-25 | 2018-01-02 | Constellation Pharmaceuticals Inc | Composés thérapeutiques de pyridazine et leurs utilisations |
CN107709364A (zh) | 2015-04-07 | 2018-02-16 | 豪夫迈·罗氏有限公司 | 具有激动剂活性的抗原结合复合体及使用方法 |
AU2016252609B2 (en) | 2015-04-20 | 2022-06-30 | Sumitomo Pharma Oncology, Inc. | Predicting response to alvocidib by mitochondrial profiling |
US10011629B2 (en) | 2015-05-01 | 2018-07-03 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
LT3294770T (lt) | 2015-05-12 | 2020-12-28 | F. Hoffmann-La Roche Ag | Vėžio gydymo ir diagnostikos būdai |
TR201911032T4 (tr) | 2015-05-18 | 2019-08-21 | Tolero Pharmaceuticals Inc | Artırılmış biyoyararlanıma sahip alvocıdıb ön ilaçları. |
CA2984003A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
US10828329B2 (en) | 2015-06-05 | 2020-11-10 | Hema-Quebec | Methods for culturing and/or differentiating hematopoietic stem cells into progenitors and uses thereof |
WO2016200835A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
AU2016274585A1 (en) | 2015-06-08 | 2017-12-14 | Genentech, Inc. | Methods of treating cancer using anti-OX40 antibodies |
WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
RU2759963C2 (ru) | 2015-08-03 | 2021-11-19 | Сумитомо Даиниппон Фарма Онколоджи, Инк. | Комбинированные терапии для лечения рака |
CN108026110B (zh) | 2015-08-26 | 2022-02-08 | 国家公共部门基金会卡洛斯三世国家癌症研究中心(F.S.P.Cnio) | 作为蛋白激酶抑制剂的稠合三环化合物 |
MX2018003633A (es) | 2015-09-25 | 2018-08-01 | Genentech Inc | Anticuerpos anti-tigit y metodos de uso. |
US11773106B2 (en) | 2015-10-16 | 2023-10-03 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US11512092B2 (en) | 2015-10-16 | 2022-11-29 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US10550126B2 (en) | 2015-10-16 | 2020-02-04 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US11365198B2 (en) | 2015-10-16 | 2022-06-21 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
CN108368121B (zh) | 2015-10-16 | 2023-01-13 | 艾伯维公司 | 制备咪唑并[1,2-a]吡咯并[2,3-e]吡嗪类化合物的方法 |
US11524964B2 (en) | 2015-10-16 | 2022-12-13 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US20180371551A1 (en) | 2015-12-03 | 2018-12-27 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
HRP20220227T1 (hr) | 2015-12-16 | 2022-04-29 | Genentech, Inc. | Postupak priprave tricikličnih spojeva inhibitora p13k i postupci upotrebe navedenih spojeva u liječenju raka |
AU2017205089B2 (en) | 2016-01-08 | 2023-10-05 | F. Hoffmann-La Roche Ag | Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies |
KR20180119632A (ko) | 2016-02-29 | 2018-11-02 | 제넨테크, 인크. | 암에 대한 치료 및 진단 방법 |
AU2017229575A1 (en) | 2016-03-08 | 2018-09-27 | Janssen Biotech, Inc. | GITR antibodies, methods, and uses |
RU2625316C1 (ru) * | 2016-04-13 | 2017-07-13 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | 2-АМИНОЗАМЕЩЕННЫЕ 6-МЕТОКСИ-4-ТРИФТОРМЕТИЛ-9Н-ПИРИМИДО[4,5b]ИНДОЛЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ПРИМЕНЕНИЕ И ПРЕДШЕСТВЕННИКИ |
US20170319688A1 (en) | 2016-04-14 | 2017-11-09 | Genentech, Inc. | Anti-rspo3 antibodies and methods of use |
ES2850428T3 (es) | 2016-04-15 | 2021-08-30 | Hoffmann La Roche | Procedimientos de monitorización y tratamiento del cáncer |
AU2017249229A1 (en) | 2016-04-15 | 2018-10-04 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
KR20190003957A (ko) | 2016-04-15 | 2019-01-10 | 제넨테크, 인크. | 암 모니터링 및 치료 방법 |
MA45146A (fr) | 2016-05-24 | 2021-03-24 | Constellation Pharmaceuticals Inc | Dérivés de pyrazolopyridine pour le traitement du cancer |
CN109476641B (zh) | 2016-05-24 | 2022-07-05 | 基因泰克公司 | Cbp/ep300的杂环抑制剂及其在治疗癌症中的用途 |
JP2019527037A (ja) | 2016-06-08 | 2019-09-26 | ジェネンテック, インコーポレイテッド | がんのための診断及び治療方法 |
CR20180598A (es) | 2016-06-22 | 2019-11-20 | Univ Vanderbilt | Moduladores alostéricos positivos del receptor muscarínico de acetilcolina m4 |
CN109963871A (zh) | 2016-08-05 | 2019-07-02 | 豪夫迈·罗氏有限公司 | 具有激动活性的多价及多表位抗体以及使用方法 |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
CA3038712A1 (en) | 2016-10-06 | 2018-04-12 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
CN110267678A (zh) | 2016-10-29 | 2019-09-20 | 霍夫曼-拉罗奇有限公司 | 抗mic抗体和使用方法 |
WO2018085803A1 (en) | 2016-11-07 | 2018-05-11 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
BR112018013879A2 (pt) | 2016-11-07 | 2018-12-11 | Univ Vanderbilt | moduladores alostéricos positivos do receptor muscarínico de acetilcolina m4 |
CN109862893B (zh) * | 2016-11-07 | 2023-02-17 | 范德比尔特大学 | 毒蕈碱型乙酰胆碱受体m4的正向别构调节剂 |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
WO2018119000A1 (en) | 2016-12-19 | 2018-06-28 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
UA124474C2 (uk) | 2016-12-22 | 2021-09-22 | Емджен Інк. | БЕНЗІЗОТІАЗОЛЬНІ, ІЗОТІАЗОЛО[3,4-b]ПІРИДИНОВІ, ХІНАЗОЛІНОВІ, ФТАЛАЗИНОВІ, ПІРИДО[2,3-d]ПІРИДАЗИНОВІ Й ПІРИДО[2,3-d]ПІРИМІДИНОВІ ПОХІДНІ ЯК ІНГІБІТОРИ G12C KRAS ДЛЯ ЛІКУВАННЯ РАКУ ЛЕГЕНІ, РАКУ ПІДШЛУНКОВОЇ ЗАЛОЗИ АБО КОЛОРЕКТАЛЬНОГО РАКУ |
CN106699755B (zh) * | 2017-01-10 | 2018-09-21 | 清华大学深圳研究生院 | 一种氮杂吖啶类化合物及其制备方法与用途 |
MX2019010295A (es) | 2017-03-01 | 2019-11-21 | Genentech Inc | Métodos de diagnóstico y terapéuticos para el cáncer. |
JP2020516638A (ja) | 2017-04-13 | 2020-06-11 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | がんを処置する方法における使用のための、インターロイキン2イムノコンジュゲート、cd40アゴニスト、および任意選択のpd−1軸結合アンタゴニスト |
JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
KR20200093518A (ko) | 2017-07-21 | 2020-08-05 | 제넨테크, 인크. | 암에 대한 치료 및 진단 방법 |
EP3665197A2 (en) | 2017-08-11 | 2020-06-17 | H. Hoffnabb-La Roche Ag | Anti-cd8 antibodies and uses thereof |
IL293443A (en) | 2017-09-08 | 2022-07-01 | Amgen Inc | kras g12c inhibitors and methods of using them |
TWI827550B (zh) | 2017-09-08 | 2024-01-01 | 美商建南德克公司 | 癌症之診斷及治療方法 |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
JP2021502066A (ja) | 2017-11-06 | 2021-01-28 | ジェネンテック, インコーポレイテッド | がんの診断及び療法 |
WO2019113174A1 (en) * | 2017-12-05 | 2019-06-13 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
TW201930311A (zh) | 2017-12-05 | 2019-08-01 | 泛德比爾特大學 | 蕈毒鹼型乙醯膽鹼受體m4之正向別構調節劑 |
KR20200135313A (ko) | 2018-02-26 | 2020-12-02 | 제넨테크, 인크. | 항-tigit 및 항-pd-l1 길항제 항체에 의한 치료를 위한 투약 |
US11090304B2 (en) | 2018-05-04 | 2021-08-17 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
JP7361722B2 (ja) | 2018-05-04 | 2023-10-16 | アムジエン・インコーポレーテツド | Kras g12c阻害剤及び同一物の使用方法 |
CA3099045A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
CN108676009B (zh) * | 2018-05-14 | 2020-04-21 | 武汉九州钰民医药科技有限公司 | 作为her2酪氨酸激酶抑制剂的嘧啶衍生物及其应用 |
WO2019226514A2 (en) | 2018-05-21 | 2019-11-28 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
JP7360396B2 (ja) | 2018-06-01 | 2023-10-12 | アムジエン・インコーポレーテツド | Kras g12c阻害剤及び同一物の使用方法 |
EP4268898A3 (en) | 2018-06-11 | 2024-01-17 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
MX2020012261A (es) | 2018-06-12 | 2021-03-31 | Amgen Inc | Inhibidores de kras g12c que comprenden un anillo de piperazina y uso de estos en el tratamiento del cancer. |
MA52968A (fr) | 2018-06-23 | 2021-04-28 | Hoffmann La Roche | Méthodes de traitement du cancer du poumon à l'aide d'un antagoniste de liaison à l'axe pd-1, d'un agent de platine et d'un inhibiteur de la topoisomérase ii |
MX2021000558A (es) | 2018-07-18 | 2021-04-13 | Genentech Inc | Metodos para tratar el cancer de pulmon con un antagonista de fijacion al eje pd-1, un antimetabolito y un agente de platino. |
AU2019310590A1 (en) | 2018-07-26 | 2021-01-14 | Sumitomo Pharma Oncology, Inc. | Methods for treating diseases associated with abnormal acvr1 expression and acvr1 inhibitors for use in the same |
CN112805267B (zh) | 2018-09-03 | 2024-03-08 | 豪夫迈·罗氏有限公司 | 用作tead调节剂的甲酰胺和磺酰胺衍生物 |
MX2021003214A (es) | 2018-09-19 | 2021-05-12 | Genentech Inc | Metodos terapeuticos y de diagnostico para el cancer de vejiga. |
EP4249917A3 (en) | 2018-09-21 | 2023-11-08 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
WO2020070239A1 (en) | 2018-10-04 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
CA3116324A1 (en) | 2018-10-18 | 2020-04-23 | Genentech, Inc. | Diagnostic and therapeutic methods for sarcomatoid kidney cancer |
JP2020090482A (ja) | 2018-11-16 | 2020-06-11 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の重要な中間体の改良合成法 |
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 |
MA55136A (fr) | 2018-11-19 | 2022-02-23 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
CN113490499A (zh) | 2018-12-04 | 2021-10-08 | 大日本住友制药肿瘤公司 | 用作治疗癌症的活性剂的cdk9抑制剂及其多晶型物 |
CN113490666A (zh) | 2018-12-19 | 2021-10-08 | 奥瑞生物药品公司 | 作为fgfr酪氨酸激酶的抑制剂的取代的吡唑并[1,5-a]吡啶化合物 |
WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
US11236069B2 (en) | 2018-12-20 | 2022-02-01 | Amgen Inc. | KIF18A inhibitors |
US20220002311A1 (en) | 2018-12-20 | 2022-01-06 | Amgen Inc. | Kif18a inhibitors |
MX2021007158A (es) | 2018-12-20 | 2021-08-16 | Amgen Inc | Heteroarilamidas utiles como inhibidores de kif18a. |
MX2021007104A (es) | 2018-12-20 | 2021-08-11 | Amgen Inc | Inhibidores de kif18a. |
JP2022519649A (ja) | 2019-02-08 | 2022-03-24 | ジェネンテック, インコーポレイテッド | がんの診断および治療方法 |
KR20210146290A (ko) | 2019-02-12 | 2021-12-03 | 스미토모 다이니폰 파마 온콜로지, 인크. | 헤테로시클릭 단백질 키나제 억제제를 포함하는 제제 |
CA3130695A1 (en) | 2019-02-27 | 2020-09-03 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies |
CA3131268A1 (en) | 2019-02-27 | 2020-09-03 | Epiaxis Therapeutics Pty Ltd | Methods and agents for assessing t-cell function and predicting response to therapy |
WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
MX2021010323A (es) | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos bicíclicos de heterociclilo y usos de este. |
JP2022525149A (ja) | 2019-03-20 | 2022-05-11 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | ベネトクラクスが失敗した急性骨髄性白血病(aml)の処置 |
AU2020245437A1 (en) | 2019-03-22 | 2021-09-30 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
AU2020270376A1 (en) | 2019-05-03 | 2021-10-07 | Genentech, Inc. | Methods of treating cancer with an anti-PD-L1 antibody |
EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
EP3972973A1 (en) | 2019-05-21 | 2022-03-30 | Amgen Inc. | Solid state forms |
CN110156792A (zh) * | 2019-06-28 | 2019-08-23 | 广州暨南生物医药研究开发基地有限公司 | 一种嘧啶并吲哚化合物及其制备方法和应用 |
CN112300279A (zh) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | 针对抗cd73抗体和变体的方法和组合物 |
JP2022542319A (ja) | 2019-08-02 | 2022-09-30 | アムジエン・インコーポレーテツド | Kif18a阻害剤 |
MX2022001295A (es) | 2019-08-02 | 2022-02-22 | Amgen Inc | Inhibidores de kif18a. |
CN114269731A (zh) | 2019-08-02 | 2022-04-01 | 美国安进公司 | Kif18a抑制剂 |
US20220372018A1 (en) | 2019-08-02 | 2022-11-24 | Amgen Inc. | Kif18a inhibitors |
CN110437149B (zh) * | 2019-08-20 | 2021-01-29 | 大连民族大学 | 抗肿瘤活性的天然萘基异喹啉类化合物及其组合物、应用 |
WO2021046159A1 (en) | 2019-09-04 | 2021-03-11 | Genentech, Inc. | Cd8 binding agents and uses thereof |
TW202126690A (zh) | 2019-09-27 | 2021-07-16 | 美商建南德克公司 | 用抗tigit和抗pd-l1拮抗劑抗體給藥治療 |
JP2022552873A (ja) | 2019-10-24 | 2022-12-20 | アムジエン・インコーポレーテツド | がんの治療におけるkras g12c及びkras g12d阻害剤として有用なピリドピリミジン誘導体 |
EP4051674A1 (en) | 2019-10-29 | 2022-09-07 | F. Hoffmann-La Roche AG | Bifunctional compounds for the treatment of cancer |
TW202132315A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ras 抑制劑 |
CR20220243A (es) | 2019-11-04 | 2022-08-04 | Revolution Medicines Inc | Inhibidores de ras |
EP4054719A1 (en) | 2019-11-04 | 2022-09-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021092171A1 (en) | 2019-11-06 | 2021-05-14 | Genentech, Inc. | Diagnostic and therapeutic methods for treatment of hematologic cancers |
EP4055017A1 (en) | 2019-11-08 | 2022-09-14 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
CR20220207A (es) | 2019-11-13 | 2022-06-06 | Genentech Inc | Compuestos terapéuticos y métodos de uso |
KR20220101125A (ko) | 2019-11-14 | 2022-07-19 | 암젠 인크 | Kras g12c 억제제 화합물의 개선된 합성 |
AR120456A1 (es) | 2019-11-14 | 2022-02-16 | Amgen Inc | Síntesis mejorada del compuesto inhibidor de g12c de kras |
WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
IL293423A (en) | 2019-12-13 | 2022-07-01 | Genentech Inc | Anti-ly6g6d antibodies and methods of use |
WO2021127404A1 (en) | 2019-12-20 | 2021-06-24 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
MX2022008305A (es) | 2020-01-07 | 2022-08-08 | Revolution Medicines Inc | Dosificacion de inhibidores de shp2 y metodos de tratamiento del cancer. |
AU2021212662A1 (en) | 2020-01-27 | 2022-08-11 | F. Hoffmann-La Roche Ag | Methods for treatment of cancer with an anti-TIGIT antagonist antibody |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
CN115698717A (zh) | 2020-04-03 | 2023-02-03 | 基因泰克公司 | 癌症的治疗和诊断方法 |
WO2021222167A1 (en) | 2020-04-28 | 2021-11-04 | Genentech, Inc. | Methods and compositions for non-small cell lung cancer immunotherapy |
AU2021293038A1 (en) | 2020-06-16 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating triple-negative breast cancer |
KR20230024368A (ko) | 2020-06-18 | 2023-02-20 | 제넨테크, 인크. | 항-tigit 항체 및 pd-1 축 결합 길항제를 사용한 치료 |
IL299131A (en) | 2020-06-18 | 2023-02-01 | Revolution Medicines Inc | Methods for delaying, preventing and treating acquired resistance to RAS inhibitors |
US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
CN116568824A (zh) | 2020-08-03 | 2023-08-08 | 基因泰克公司 | 淋巴瘤的诊断和治疗方法 |
WO2022036146A1 (en) | 2020-08-12 | 2022-02-17 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
IL301062A (en) | 2020-09-03 | 2023-05-01 | Revolution Medicines Inc | Use of SOS1 inhibitors to treat malignancies with SHP2 mutations |
EP4214209A1 (en) | 2020-09-15 | 2023-07-26 | Revolution Medicines, Inc. | Indole derivatives as ras inhibitors in the treatment of cancer |
CA3196277A1 (en) | 2020-09-23 | 2022-03-31 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
AU2021358031A1 (en) | 2020-10-05 | 2023-05-04 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
TW202229291A (zh) * | 2020-12-07 | 2022-08-01 | 大陸商北京泰德製藥股份有限公司 | Sos1抑制劑、包含其的藥物組合物及其用途 |
US20230107642A1 (en) | 2020-12-18 | 2023-04-06 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
EP4267250A1 (en) | 2020-12-22 | 2023-11-01 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
CR20230382A (es) | 2021-02-12 | 2023-09-06 | Hoffmann La Roche | Derivados de tetrahidroazepina bicíclicos para el tratamiento del cáncer |
WO2022222875A1 (zh) * | 2021-04-19 | 2022-10-27 | 昆药集团股份有限公司 | 一种苯并嘧啶三环衍生物及其制备方法和应用 |
WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
BR112023022819A2 (pt) | 2021-05-05 | 2024-01-16 | Revolution Medicines Inc | Compostos, composição farmacêutica, conjugados e métodos para tratar câncer em um sujeito, para tratar um distúrbio e para inibir uma proteína ras em uma célula |
CR20230558A (es) | 2021-05-05 | 2024-01-24 | Revolution Medicines Inc | Inhibidores de ras para el tratamiento del cáncer |
KR20240026948A (ko) | 2021-05-25 | 2024-02-29 | 에라스카, 아이엔씨. | 황 함유 헤테로방향족 트리사이클릭 kras 억제제 |
WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
WO2023018699A1 (en) | 2021-08-10 | 2023-02-16 | Erasca, Inc. | Selective kras inhibitors |
AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
US20230202984A1 (en) | 2021-11-24 | 2023-06-29 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2023097194A2 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic compounds and methods of use |
TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024033457A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033388A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
WO2024033389A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
WO2024085242A2 (en) | 2022-10-21 | 2024-04-25 | Kawasaki Institute Of Industrial Promotion | Non-fouling or super stealth vesicle |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2949466A (en) | 1958-03-04 | 1960-08-16 | Parke Davis & Co | Pyrimidine compounds and means of producing the same |
GB1199768A (en) | 1966-10-31 | 1970-07-22 | Pfizer & Co C | Nitrogen Heterocycles and process for their preparation |
US3812127A (en) | 1966-10-31 | 1974-05-21 | Pfizer | 4-(quinolin-4-yl)piperazine-1-carboxylic acid esters |
US3702849A (en) | 1967-10-26 | 1972-11-14 | Pfizer | 4-(isoquinolin-1-yl) piperazine-1-carboxylic acid esters |
US3517005A (en) | 1967-10-26 | 1970-06-23 | Pfizer & Co C | Certain 2- and 4-substituted quinazolines |
CH530412A (de) | 1968-07-15 | 1972-11-15 | Ciba Geigy Ag | Verfahren zur Herstellung von (1)Benzothieno-(2,3-d)pyrimidinen |
US3755583A (en) * | 1970-06-05 | 1973-08-28 | Chas0!nhx | |
FR2137271B1 (cs) | 1971-05-11 | 1973-05-11 | Progil | |
GB1417029A (en) | 1973-03-07 | 1975-12-10 | Pfizer Ltd | Quinazoline-derived amines |
US3971783A (en) | 1973-03-07 | 1976-07-27 | Pfizer Inc. | 4-Aminoquinazoline derivatives as cardiac stimulants |
SE435380B (sv) | 1976-06-15 | 1984-09-24 | Pfizer | Forfarande for framstellning av kinazolinforeningar |
US4466965A (en) | 1982-07-26 | 1984-08-21 | American Hospital Supply Corporation | Phthalazine compounds, compositions and use |
WO1984001151A1 (en) | 1982-09-24 | 1984-03-29 | Beecham Group Plc | Amino-azabicycloalkyl derivatives as dopamine antagonists |
IN157280B (cs) | 1983-07-15 | 1986-02-22 | Hoechst India | |
KR930009443B1 (ko) | 1985-03-14 | 1993-10-04 | 상꾜 가부시끼가이샤 | 페녹시알킬아미노 피리미딘 유도체의 제조방법 |
US5141941A (en) | 1988-11-21 | 1992-08-25 | Ube Industries, Ltd. | Aralkylamine derivatives, and fungicides containing the same |
GB8912336D0 (en) | 1989-05-30 | 1989-07-12 | Smithkline Beckman Intercredit | Compounds |
US5034393A (en) | 1989-07-27 | 1991-07-23 | Dowelanco | Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives |
JPH03173872A (ja) | 1989-09-14 | 1991-07-29 | Ube Ind Ltd | アミノピリミジン誘導体、その製造方法及び殺虫・殺菌剤 |
GB9022644D0 (en) | 1990-10-18 | 1990-11-28 | Ici Plc | Heterocyclic compounds |
SK400992A3 (en) | 1990-11-06 | 1995-08-09 | Pfizer | Quinazolines derivatives for enhancing antitumor activity |
JP2762430B2 (ja) | 1991-01-18 | 1998-06-04 | 宇部興産株式会社 | アラルキルアミノピリミジン類の製法 |
DE9290018U1 (de) | 1991-02-20 | 1993-10-14 | Pfizer | 2,4-Diaminochinazolin-Derivate zur Verbesserung der Antitumor-Aktivität |
ES2108120T3 (es) * | 1991-05-10 | 1997-12-16 | Rhone Poulenc Rorer Int | Compuestos bis arilicos y heteroarilicos mono- y biciclicos que inhiben tirosina quinasa receptora de egf y/o pdgf. |
NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
DE4131029A1 (de) | 1991-09-18 | 1993-07-29 | Basf Ag | Substituierte pyrido (2,3-d) pyrimidine als antidots |
PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
US5187168A (en) | 1991-10-24 | 1993-02-16 | American Home Products Corporation | Substituted quinazolines as angiotensin II antagonists |
AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
JP3173872B2 (ja) | 1992-05-15 | 2001-06-04 | オリンパス光学工業株式会社 | 光学素子成形用型および該成形用型を用いた光学素子の成形方法 |
JPH0641134A (ja) | 1992-07-21 | 1994-02-15 | Nippon Soda Co Ltd | ピリミドプテリジン誘導体及びその製造方法 |
GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
TW444018B (en) | 1992-12-17 | 2001-07-01 | Pfizer | Pyrazolopyrimidines |
JPH06220059A (ja) | 1993-01-28 | 1994-08-09 | Tanabe Seiyaku Co Ltd | 縮合ピリミジン誘導体及びその製法 |
DE4308014A1 (de) | 1993-03-13 | 1994-09-15 | Hoechst Schering Agrevo Gmbh | Kondensierte Stickstoffheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide |
-
1995
- 1995-01-04 IL IL11224895A patent/IL112248A0/xx unknown
- 1995-01-23 WO PCT/US1995/000911 patent/WO1995019970A1/en active IP Right Grant
- 1995-01-23 NZ NZ281404A patent/NZ281404A/xx unknown
- 1995-01-23 GE GEAP19953312A patent/GEP20002330B/en unknown
- 1995-01-23 SK SK895-96A patent/SK89596A3/sk unknown
- 1995-01-23 PL PL95315632A patent/PL315632A1/xx unknown
- 1995-01-23 AU AU18334/95A patent/AU686339B2/en not_active Ceased
- 1995-01-23 HU HU9602016A patent/HU222572B1/hu not_active IP Right Cessation
- 1995-01-23 EP EP95910116A patent/EP0741711A1/en not_active Withdrawn
- 1995-01-23 JP JP51972195A patent/JP3965439B2/ja not_active Expired - Fee Related
- 1995-01-23 MD MD96-0211A patent/MD1616G2/ro unknown
- 1995-01-23 MX MX9602109A patent/MX9602109A/es unknown
- 1995-01-23 CN CNB951913182A patent/CN1137100C/zh not_active Expired - Fee Related
- 1995-01-23 CZ CZ961971A patent/CZ197196A3/cs unknown
- 1995-01-24 HR HR08/358,352A patent/HRP950033A2/hr not_active Application Discontinuation
-
1996
- 1996-05-20 BG BG100615A patent/BG63432B1/bg unknown
- 1996-07-15 FI FI962855A patent/FI114098B/fi active
- 1996-07-24 NO NO963093A patent/NO307182B1/no unknown
-
1997
- 1997-03-06 US US08/811,803 patent/US6596726B1/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
FI962855A (fi) | 1996-09-13 |
FI962855A0 (fi) | 1996-07-15 |
CN1139430A (zh) | 1997-01-01 |
HU222572B1 (hu) | 2003-08-28 |
IL112248A0 (en) | 1995-03-30 |
CZ197196A3 (en) | 1997-07-16 |
FI114098B (fi) | 2004-08-13 |
NO963093D0 (no) | 1996-07-24 |
AU1833495A (en) | 1995-08-08 |
NO963093L (no) | 1996-07-24 |
PL315632A1 (en) | 1996-11-25 |
NZ281404A (en) | 1999-05-28 |
SK89596A3 (en) | 1997-08-06 |
NO307182B1 (no) | 2000-02-21 |
EP0741711A1 (en) | 1996-11-13 |
CN1137100C (zh) | 2004-02-04 |
JPH09508126A (ja) | 1997-08-19 |
MD1616G2 (ro) | 2001-11-30 |
HU9602016D0 (en) | 1996-09-30 |
AU686339B2 (en) | 1998-02-05 |
MD960211A (en) | 1998-04-30 |
JP3965439B2 (ja) | 2007-08-29 |
BG63432B1 (bg) | 2002-01-31 |
HUT74590A (en) | 1997-01-28 |
WO1995019970A1 (en) | 1995-07-27 |
GEP20002330B (en) | 2000-12-25 |
MX9602109A (es) | 1997-05-31 |
MD1616F2 (en) | 2001-02-28 |
US6596726B1 (en) | 2003-07-22 |
BG100615A (bg) | 1997-02-28 |
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