TW561154B - Isothiazole derivatives useful as anticancer agents - Google Patents

Isothiazole derivatives useful as anticancer agents Download PDF

Info

Publication number: TW561154B
Authority: TW; Taiwan
Prior art keywords: ureido; methyl; carboxamidine; benzyloxy; isothiazole
Prior art date: 1998-06-04

Application number

TW088108991A

Other languages

English (en)

Chinese (zh)

Inventor

Eric Robert Larson

Mark Carl Noe

Thomas George Gant

Original Assignee

Pfizer Prod Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-06-04

Filing date

1999-05-31

Publication date

2003-11-11

1999-05-31 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2003-11-11 Application granted granted Critical

2003-11-11 Publication of TW561154B publication Critical patent/TW561154B/zh

Links

239000002246 antineoplastic agent Substances 0.000 title description 3
150000003854 isothiazoles Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 236
238000000034 method Methods 0.000 claims abstract description 98
150000003839 salts Chemical class 0.000 claims abstract description 38
-1 Methylamino, dimethylamino, isopropylamino, hydroxy, pyrrolidinyl Chemical group 0.000 claims description 927
238000011049 filling Methods 0.000 claims description 187
230000002079 cooperative effect Effects 0.000 claims description 104
239000004202 carbamide Substances 0.000 claims description 97
150000001412 amines Chemical class 0.000 claims description 73
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 64
REOJLIXKJWXUGB-UHFFFAOYSA-N mofebutazone Chemical group O=C1C(CCCC)C(=O)NN1C1=CC=CC=C1 REOJLIXKJWXUGB-UHFFFAOYSA-N 0.000 claims description 51
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 47
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 45
BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 41
125000000623 heterocyclic group Chemical group 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 16
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125000005843 halogen group Chemical group 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
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QKHKBGUGCQSJIO-UHFFFAOYSA-N 1,2-thiazole-4-carboximidamide Chemical compound NC(=N)C=1C=NSC=1 QKHKBGUGCQSJIO-UHFFFAOYSA-N 0.000 claims description 7
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238000006467 substitution reaction Methods 0.000 claims description 6
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125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
230000008719 thickening Effects 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000002053 thietanyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000002992 thymic effect Effects 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000005490 tosylate group Chemical class 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
210000000626 ureter Anatomy 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
208000037965 uterine sarcoma Diseases 0.000 description 1
206010046885 vaginal cancer Diseases 0.000 description 1
208000013139 vaginal neoplasm Diseases 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/58—Derivatives of thiocarboxylic acids, the doubly-bound oxygen atoms being replaced by nitrogen atoms, e.g. imino-thio ethers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

TW088108991A 1998-06-04 1999-05-31 Isothiazole derivatives useful as anticancer agents TW561154B (en)

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US8796398P	1998-06-04	1998-06-04

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CN (2)	CN1616386A (2)
AP (1)	AP1309A (2)
AR (1)	AR016725A1 (2)
AT (1)	ATE275553T1 (2)
AU (1)	AU3342199A (2)
BG (1)	BG65104B1 (2)
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CA (2)	CA2475113C (2)
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CZ (1)	CZ298559B6 (2)
DE (1)	DE69920009T2 (2)
EA (1)	EA004935B1 (2)
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MA (1)	MA26638A1 (2)
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Families Citing this family (239)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5849769A (en) *	1994-08-24	1998-12-15	Medivir Ab	N-arylalkyl-N-heteroarylurea and guandine compounds and methods of treating HIV infection
WO1999010349A1 (en)	1997-08-22	1999-03-04	Zeneca Limited	Oxindolylquinazoline derivatives as angiogenesis inhibitors
UA60365C2 (uk) *	1998-06-04	2003-10-15	Пфайзер Продактс Інк.	Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця
ATE538794T1 (de)	1999-01-13	2012-01-15	Bayer Healthcare Llc	Gamma carboxyarylsubstituierte diphenylharnstoffverbindungen als p38 kinasehemmer
US7351834B1 (en)	1999-01-13	2008-04-01	Bayer Pharmaceuticals Corporation	ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US8124630B2 (en)	1999-01-13	2012-02-28	Bayer Healthcare Llc	ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7125875B2 (en)	1999-04-15	2006-10-24	Bristol-Myers Squibb Company	Cyclic protein tyrosine kinase inhibitors
PL215901B1 (pl)	1999-04-15	2014-02-28	Bristol Myers Squibb Co	Cykliczny inhibitor bialkowych kinaz tyrozynowych, jego zastosowanie oraz kompozycja farmaceutyczna zawierajaca taki zwiazek
HN2000000051A (es) *	1999-05-19	2001-02-02	Pfizer Prod Inc	Derivados heterociclicos utiles como agentes anticancerosos
CN1427839A (zh)	2000-03-16	2003-07-02	根索福特股份有限公司	含有核酸结合部分的带电荷化合物及其用途
US7078536B2 (en)	2001-03-14	2006-07-18	Genesoft Pharmaceuticals, Inc.	Charged compounds comprising a nucleic acid binding moiety and uses therefor
EP1307462A2 (en)	2000-08-09	2003-05-07	Agouron Pharmaceuticals, Inc.	Pyrazole-thiazole compounds, pharmaceutical compositions containing them, and methods of their use for inhibiting cyclin-dependent kinases
WO2002014305A2 (en)	2000-08-17	2002-02-21	Lumera Corporation	Design and synthesis of advanced nlo materials for electro-optic applications
ATE295354T1 (de)	2000-08-18	2005-05-15	Agouron Pharma	Heterozyklische-hydroximino-fluorene und ihre verwendung zur inhibierung von proteinkinasen
DE60137273D1 (de)	2000-10-20	2009-02-12	Eisai R&D Man Co Ltd	Verfahren zur Herstellung von 4-Phenoxy chinolin Derivaten
CZ20031315A3 (cs) *	2000-11-28	2004-04-14	Pfizer Products Inc.	Soli isothiazolkarboxamidu a jejich použití jako prostředků proti hyperproliferaci
EP1343782B1 (en)	2000-12-21	2009-05-06	SmithKline Beecham Corporation	Pyrimidineamines as angiogenesis modulators
BRPI0116728B1 (pt)	2001-01-05	2018-10-30	Pfizer Inc.	anticorpos para receptor de fator de crescimento i semelhante à insulina
US6699866B2 (en)	2001-04-17	2004-03-02	Sepracor Inc.	Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof
AU2002345792A1 (en)	2001-06-21	2003-01-08	Pfizer Inc.	Thienopyridine and thienopyrimidine anticancer agents
HN2002000156A (es)	2001-07-06	2003-11-27	Inc Agouron Pharmaceuticals	Derivados de benzamida tiazol y composiciones farmaceuticas para inhibir la proliferacion de celulas y metodos para su utilización.
US7265134B2 (en)	2001-08-17	2007-09-04	Merck & Co., Inc.	Tyrosine kinase inhibitors
AR039067A1 (es)	2001-11-09	2005-02-09	Pfizer Prod Inc	Anticuerpos para cd40
US20030143165A1 (en) *	2002-01-25	2003-07-31	Allan Evans	NSAID-containing topical formulations that demonstrate chemopreventive activity
MXPA04007832A (es)	2002-02-11	2005-09-08	Bayer Pharmaceuticals Corp	Aril-ureas con actividad inhibitoria de angiogenesis.
WO2003068229A1 (en)	2002-02-11	2003-08-21	Bayer Pharmaceuticals Corporation	Pyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors
US20040023961A1 (en) *	2002-02-11	2004-02-05	Bayer Corporation	Aryl ureas with raf kinase and angiogenisis inhibiting activity
WO2003092595A2 (en)	2002-05-02	2003-11-13	Merck & Co., Inc	Tyrosine kinase inhibitors
US6989451B2 (en) *	2002-06-04	2006-01-24	Valeant Research & Development	Heterocyclic compounds and uses thereof
EP1521577A1 (en) *	2002-06-13	2005-04-13	QLT, Inc.	Methods of using isothiazole derivatives to treat cancer or inflammation
BR0312023A (pt)	2002-06-27	2005-03-22	Novo Nordisk As	Composto, composto ativador da glicose cinase, método para evitar a hipoglicemia, uso de um composto, e, composição farmacêutica
EP1527071A1 (en) *	2002-07-25	2005-05-04	Pfizer Products Inc.	Isothiazole derivatives useful as anticancer agents
ATE425753T1 (de)	2002-08-02	2009-04-15	Genesoft Pharmaceuticals Inc	Biaryl-verbindungen mit antiinfektiver wirkung
CA2495962A1 (en) *	2002-08-19	2004-03-04	Pfizer Products Inc.	Combination therapy for hyperproliferative diseases
EP1562931A2 (en)	2002-10-25	2005-08-17	Genesoft Pharmaceuticals, Inc.	Anti-infective biaryl compounds
AU2003297822A1 (en)	2002-12-10	2004-06-30	Oscient Pharmaceuticals Corporation	Antibacterial compounds having a (pyrrole carboxamide)-(benzamide)-(imidazole carboxamide) motif
WO2004056806A1 (en)	2002-12-19	2004-07-08	Pfizer Inc.	2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases
CA2513140A1 (en) *	2003-01-27	2004-08-12	Pfizer Products Inc.	Isothiazole derivatives
US7557129B2 (en)	2003-02-28	2009-07-07	Bayer Healthcare Llc	Cyanopyridine derivatives useful in the treatment of cancer and other disorders
NZ543102A (en) *	2003-04-24	2008-12-24	Incyte Corp	Aza spiro alkane derivatives as inhibitors of metalloproteases
WO2004113274A2 (en)	2003-05-20	2004-12-29	Bayer Pharmaceuticals Corporation	Diaryl ureas with kinase inhibiting activity
KR101254371B1 (ko)	2003-07-18	2013-05-02	암젠 프레몬트 인코포레이티드	간세포 성장인자에 결합하는 분리된 항체
EA010485B1 (ru)	2003-07-23	2008-10-30	Байер Фамэсьютиклс Копэрейшн	Производное n,n'-дифенилмочевины, фармацевтическая композиция (варианты) и способ лечения и предупреждения заболеваний и состояний с его использованием (варианты)
HN2004000285A (es)	2003-08-04	2006-04-27	Pfizer Prod Inc	ANTICUERPOS DIRIGIDOS A c-MET
AR045563A1 (es)	2003-09-10	2005-11-02	Warner Lambert Co	Anticuerpos dirigidos a m-csf
US7683172B2 (en)	2003-11-11	2010-03-23	Eisai R&D Management Co., Ltd.	Urea derivative and process for preparing the same
JP4834840B2 (ja)	2004-01-06	2011-12-14	ノヴォノルディスクアー／エス	ヘテロアリール尿素およびグルコキナーゼ活性化剤としてのその使用
ES2246687B2 (es) *	2004-02-11	2006-11-16	Miguel Muñoz Saez	Utilizacion de antagonistas no peptidicos de receptores nk1 para la produccion de apoptosis en celulas tumorales.
WO2005081997A2 (en) *	2004-02-20	2005-09-09	The Scripps Research Institute	Isothiazole based protein kinase inhibitors
WO2005102327A1 (en) *	2004-04-20	2005-11-03	Pfizer Products Inc.	Dosage forms and methods of treatment using vegfr inhibitors
CN101010315A (zh)	2004-04-30	2007-08-01	拜耳制药公司	用于治疗癌症的取代的吡唑基脲衍生物
TW200538104A (en) *	2004-05-17	2005-12-01	Pfizer Prod Inc	Phenyl derivatives for the treatment of abnormal cell growth
KR20070036130A (ko)	2004-07-16	2007-04-02	화이자 프로덕츠 인코포레이티드	항-아이지에프-1알 항체를 사용하는 비-혈액학적악성종양에 대한 조합 치료
BR122020017756B1 (pt)	2004-08-26	2022-02-15	Pfizer Inc	Uso de compostos de aminoeteroarila enantiomericamente puros na preparação de um medicamento para o tratamento de crescimento celular anormal em um mamífero
PT1784183E (pt) *	2004-08-26	2012-03-09	Pfizer	Processos para a preparação de derivados de isotiazole
EP2364699A1 (en)	2004-09-13	2011-09-14	Eisai R&D Management Co., Ltd.	Joint use of sulfonamide based compound with angiogenesis inhibitor
US8772269B2 (en)	2004-09-13	2014-07-08	Eisai R&D Management Co., Ltd.	Use of sulfonamide-including compounds in combination with angiogenesis inhibitors
AU2005283422C1 (en)	2004-09-17	2017-02-02	Eisai R & D Management Co., Ltd.	Medicinal composition
MX2007006230A (es)	2004-11-30	2007-07-25	Amgen Inc	Quinolinas y analogos de quinazolinas y su uso como medicamentos para tratar cancer.
US7429667B2 (en) *	2005-01-20	2008-09-30	Ardea Biosciences, Inc.	Phenylamino isothiazole carboxamidines as MEK inhibitors
CA2601157A1 (en)	2005-03-16	2006-09-28	Osi Pharmaceuticals, Inc.	Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors
US20060216288A1 (en) *	2005-03-22	2006-09-28	Amgen Inc	Combinations for the treatment of cancer
CA2603093A1 (en)	2005-03-31	2006-10-05	Agensys, Inc.	Antibodies and related molecules that bind to 161p2f10b proteins
CA2763671A1 (en)	2005-04-26	2006-11-02	Pfizer Inc.	P-cadherin antibodies
US7582769B2 (en)	2005-07-08	2009-09-01	Novo Nordisk A/S	Dicycloalkyl urea glucokinase activators
WO2007015578A1 (ja)	2005-08-02	2007-02-08	Eisai R & D Management Co., Ltd.	血管新生阻害物質の効果を検定する方法
CA2621371C (en)	2005-09-07	2018-05-15	Amgen Fremont Inc.	Human monoclonal antibodies to activin receptor-like kinase-1
AU2006292278B2 (en)	2005-09-20	2012-03-08	Osi Pharmaceuticals, Inc.	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
US20080108664A1 (en)	2005-12-23	2008-05-08	Liu Belle B	Solid-state form of AMG 706 and pharmaceutical compositions thereof
AR059066A1 (es)	2006-01-27	2008-03-12	Amgen Inc	Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf)
ATE489380T1 (de) *	2006-02-10	2010-12-15	Amgen Inc	Hydratformen von amg706
US7842836B2 (en)	2006-04-11	2010-11-30	Ardea Biosciences	N-aryl-N'alkyl sulfamides as MEK inhibitors
MX2008013097A (es) *	2006-04-18	2008-10-27	Ardea Biosciences Inc	Piridona sulfonamidas y piridona sulfamidas como inhibidores de metiletilcetona.
EA200802058A1 (ru)	2006-05-09	2009-06-30	Пфайзер Продактс Инк.	Производные циклоалкиламинокислот и их фармацевтические композиции
RU2448708C3 (ru)	2006-05-18	2017-09-28	Эйсай Ар Энд Ди Менеджмент Ко., Лтд.	Противоопухолевое средство против рака щитовидной железы
US7910108B2 (en) *	2006-06-05	2011-03-22	Incyte Corporation	Sheddase inhibitors combined with CD30-binding immunotherapeutics for the treatment of CD30 positive diseases
UA95480C2 (uk) *	2006-06-08	2011-08-10	Елі Ліллі Енд Компані	Заміщені карбоксаміди
US7932390B2 (en)	2006-06-29	2011-04-26	Hoffman-La Roche Inc.	Substituted thieno[3,2-C]pyridine carboxylic acid derivatives
PE20080403A1 (es)	2006-07-14	2008-04-25	Amgen Inc	Derivados heterociclicos fusionados y metodos de uso
US8217177B2 (en)	2006-07-14	2012-07-10	Amgen Inc.	Fused heterocyclic derivatives and methods of use
CN101511793B (zh)	2006-08-28	2011-08-03	卫材R&D管理有限公司	针对未分化型胃癌的抗肿瘤剂
EP2125781A2 (en)	2006-12-20	2009-12-02	Amgen Inc.	Substituted heterocycles and methods of use
AU2008205252B2 (en)	2007-01-09	2013-02-21	Amgen Inc.	Bis-aryl amide derivatives useful for the treatment of cancer
CN101600694A (zh)	2007-01-29	2009-12-09	卫材R&D管理有限公司	未分化型胃癌治疗用组合物
AU2008219166B2 (en)	2007-02-16	2013-05-16	Amgen Inc.	Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors
KR20090115749A (ko) *	2007-02-26	2009-11-05	산텐 세이야꾸 가부시키가이샤	우레이드기와 아미노카르보닐기를 치환기로서 갖는 신규 피롤 유도체
CA2683559C (en)	2007-04-13	2019-09-24	Dana Farber Cancer Institute, Inc.	Methods for treating cancer resistant to erbb therapeutics
US20100255004A1 (en) *	2007-04-13	2010-10-07	Dana Farber Cancer Institute	Receptor tyrosine kinase profiling
US8509487B2 (en) *	2007-04-19	2013-08-13	Avago Technologies General Ip (Singapore) Pte. Ltd.	System and method for optically measuring a parameter of an object
MX2010001636A (es)	2007-08-14	2010-03-15	Hoffmann La Roche	Derivados de pirazolo[3,4-d]-pirimidina como agentes antiproliferativos.
ES2650224T3 (es)	2007-08-21	2018-01-17	Amgen, Inc.	Proteínas de unión al antígeno C-FMS humano
KR101513326B1 (ko)	2007-11-09	2015-04-17	에자이 알앤드디 매니지먼트 가부시키가이샤	혈관 신생 저해 물질과 항종양성 백금 착물의 병용
US20100029491A1 (en) *	2008-07-11	2010-02-04	Maike Schmidt	Methods and compositions for diagnostic use for tumor treatment
AU2009329994B2 (en)	2008-12-23	2014-04-03	Genentech, Inc.	Methods and compositions for diagnostic use in cancer patients
WO2010099139A2 (en)	2009-02-25	2010-09-02	Osi Pharmaceuticals, Inc.	Combination anti-cancer therapy
US20110171124A1 (en)	2009-02-26	2011-07-14	Osi Pharmaceuticals, Inc.	In situ methods for monitoring the EMT status of tumor cells in vivo
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
EP2401614A1 (en)	2009-02-27	2012-01-04	OSI Pharmaceuticals, LLC	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
MY173526A (en)	2009-03-25	2020-01-31	Genentech Inc	Novel anti-?5?1 antibodies and uses thereof
CN102482715A (zh)	2009-07-13	2012-05-30	霍夫曼-拉罗奇有限公司	用于癌症治疗的诊断方法和组合物
WO2011014726A1 (en)	2009-07-31	2011-02-03	Osi Pharmaceuticals, Inc.	Mtor inhibitor and angiogenesis inhibitor combination therapy
DK2468281T3 (en)	2009-08-19	2016-03-21	Eisai R&D Man Co Ltd	Quinolinderivatholdig pharmaceutical composition
AU2010297344A1 (en)	2009-09-17	2012-02-23	F. Hoffmann-La Roche Ag	Methods and compositions for diagnostics use in cancer patients
WO2011073521A1 (en)	2009-12-15	2011-06-23	Petri Salven	Methods for enriching adult-derived endothelial progenitor cells and uses thereof
JP6214161B2 (ja)	2009-12-21	2017-10-18	ジェネンテック，インコーポレイテッド	抗体製剤
EP2534153B2 (en)	2010-02-12	2024-05-22	Pfizer Inc.	Salts and polymorphs of 8-fluoro-2-{4-[(methylamino}methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one
CA2783665A1 (en)	2010-03-03	2011-09-09	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
CA2783656A1 (en)	2010-03-03	2011-09-09	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
WO2011153224A2 (en)	2010-06-02	2011-12-08	Genentech, Inc.	Diagnostic methods and compositions for treatment of cancer
ES2611479T3 (es)	2010-06-16	2017-05-09	University Of Pittsburgh- Of The Commonwealth System Of Higher Education	Anticuerpos contra endoplasmina y su uso
WO2011161217A2 (en)	2010-06-23	2011-12-29	Palacký University in Olomouc	Targeting of vegfr2
WO2011162343A1 (ja)	2010-06-25	2011-12-29	エーザイ・アール・アンド・ディー・マネジメント株式会社	キナーゼ阻害作用を有する化合物の併用による抗腫瘍剤
SG187592A1 (en)	2010-07-23	2013-03-28	Univ Boston	Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery
WO2012042421A1 (en)	2010-09-29	2012-04-05	Pfizer Inc.	Method of treating abnormal cell growth
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
GB201103578D0 (en)	2011-03-02	2011-04-13	Sabrepharm Ltd	Dipyridinium derivatives
UA112539C2 (uk)	2011-03-03	2016-09-26	Новартіс Аг	Спосіб одержання похідних 2-карбоксамідциклоаміносечовини
CN103703000B (zh)	2011-03-23	2015-11-25	安姆根有限公司	Cdk4/6和flt3的稠合三环双重抑制剂
CN103402519B (zh)	2011-04-18	2015-11-25	卫材R&D管理有限公司	肿瘤治疗剂
EP2702173A1 (en)	2011-04-25	2014-03-05	OSI Pharmaceuticals, LLC	Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment
JP6038128B2 (ja)	2011-06-03	2016-12-07	エーザイ・アール・アンド・ディー・マネジメント株式会社	レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー
EP2734205B1 (en)	2011-07-21	2018-03-21	Tolero Pharmaceuticals, Inc.	Heterocyclic protein kinase inhibitors
US9745288B2 (en)	2011-08-16	2017-08-29	Indiana University Research And Technology Corporation	Compounds and methods for treating cancer by inhibiting the urokinase receptor
ES2623652T3 (es)	2011-12-28	2017-07-11	Allergan, Inc.	Derivados de 3-fenil-5-ureidoisotiazol-4-carboximida y 3-amino-5-fenilisotiazol como inhibidores de cinasa
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
WO2013152252A1 (en)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
CN103508961B (zh) *	2012-06-26	2015-07-22	中美冠科生物技术（太仓）有限公司	抗肿瘤药物
WO2014036022A1 (en)	2012-08-29	2014-03-06	Amgen Inc.	Quinazolinone compounds and derivatives thereof
DK2909181T3 (da)	2012-10-16	2017-11-20	Tolero Pharmaceuticals Inc	PKM2-modulatorer og fremgangsmåder til anvendelse deraf
AU2013364953A1 (en)	2012-12-21	2015-04-30	Eisai R&D Management Co., Ltd.	Amorphous form of quinoline derivative, and method for producing same
CN110538322A (zh)	2013-03-13	2019-12-06	豪夫迈·罗氏有限公司	抗体配制剂
PL2968650T3 (pl)	2013-03-14	2019-05-31	Panoptica Inc	Preparaty do oczu do dostarczania leku do tylnego fragmentu oka
MX394360B (es)	2013-03-14	2025-03-24	Sumitomo Pharma Oncology Inc	Inhibidores de jak2 y alk2 y metodos para su uso.
EP2997377B1 (en)	2013-05-14	2018-07-18	Eisai R&D Management Co., Ltd.	Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds
EP3126521B1 (en)	2014-04-04	2019-03-20	Crown Bioscience, Inc. (Taicang)	Hnf4g-rspo2 fusion gene
PT3524595T (pt)	2014-08-28	2022-09-19	Eisai R&D Man Co Ltd	Derivado de quinolina altamente puro e método para produção do mesmo
JP7072384B2 (ja)	2014-09-15	2022-05-20	ジェネンテック，インコーポレイテッド	抗体製剤
ES2863601T3 (es)	2014-09-17	2021-10-11	Panoptica Inc	Formulaciones oculares para administración de fármacos y protección del segmento anterior del ojo
US9353093B2 (en)	2014-10-07	2016-05-31	Allergan, Inc.	Indole-1-carboxamides as kinase inhibitors
US9403803B2 (en)	2014-10-08	2016-08-02	Allergan, Inc.	Indole-3-carboxamides as kinase inhibitors
US9359336B2 (en)	2014-10-09	2016-06-07	Allergan, Inc.	Heterocycle-substituted pyridyl benzothiophenes as kinase inhibitors
US9371314B2 (en)	2014-10-09	2016-06-21	Allergan, Inc.	Pyridyl benzothiophenes as kinase inhibitors
ES2746839T3 (es)	2014-12-18	2020-03-09	Pfizer	Derivados de pirimidina y triazina y su uso como inhibidores de AXL
US11083755B2 (en)	2015-01-08	2021-08-10	The Board Of Trustees Of The Leland Stanford Junior University	Factors and cells that provide for induction of bone, bone marrow, and cartilage
AU2016224583B2 (en)	2015-02-25	2021-06-03	Eisai R&D Management Co., Ltd.	Method for suppressing bitterness of quinoline derivative
KR102662228B1 (ko)	2015-03-04	2024-05-02	머크 샤프 앤드 돔 코포레이션	암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합
US9901574B2 (en)	2015-04-20	2018-02-27	Tolero Pharmaceuticals, Inc.	Predicting response to alvocidib by mitochondrial profiling
ES2739749T3 (es)	2015-05-18	2020-02-03	Tolero Pharmaceuticals Inc	Profármacos de alvocidib que tienen biodisponibilidad aumentada
BR112017027227B1 (pt)	2015-06-16	2023-12-12	Eisai R&D Management Co., Ltd	Agente anti-câncer
MX2018001289A (es)	2015-08-03	2018-04-30	Tolero Pharmaceuticals Inc	Terapias de combinacion para el tratamiento del cancer.
JP6553726B2 (ja)	2015-08-20	2019-07-31	エーザイ・アール・アンド・ディー・マネジメント株式会社	腫瘍治療剤
GB2543550A (en)	2015-10-21	2017-04-26	Hox Therapeutics Ltd	Peptides
CN108601752A (zh)	2015-12-03	2018-09-28	安吉奥斯医药品有限公司	用于治疗mtap缺失型癌症的mat2a抑制剂
WO2018094275A1 (en)	2016-11-18	2018-05-24	Tolero Pharmaceuticals, Inc.	Alvocidib prodrugs and their use as protein kinase inhibitors
KR20190099260A (ko)	2016-12-19	2019-08-26	톨레로 파마수티컬스, 인크.	프로파일링 펩티드 및 감도 프로파일링을 위한 방법
WO2018119183A2 (en)	2016-12-22	2018-06-28	Amgen Inc.	Kras g12c inhibitors and methods of using the same
JP6581320B2 (ja)	2017-02-08	2019-09-25	エーザイ・アール・アンド・ディー・マネジメント株式会社	腫瘍治療用医薬組成物
EP3624800A4 (en)	2017-05-16	2021-02-17	Eisai R&D Management Co., Ltd.	TREATMENT OF HEPATOCELLULAR CARCINOMA
EA201992781A1 (ru)	2017-05-22	2020-04-01	Эмджен Инк.	Ингибиторы g12c kras и способы их применения
MA50077A (fr)	2017-09-08	2020-07-15	Amgen Inc	Inhibiteurs de kras g12c et leurs procédés d'utilisation
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
WO2019213516A1 (en)	2018-05-04	2019-11-07	Amgen Inc.	Kras g12c inhibitors and methods of using the same
ES2995514T3 (en)	2018-05-04	2025-02-10	Amgen Inc	Kras g12c inhibitors and methods of using the same
EP3790886B1 (en)	2018-05-10	2024-06-26	Amgen Inc.	Kras g12c inhibitors for the treatment of cancer
ES2938987T3 (es)	2018-06-01	2023-04-18	Amgen Inc	Inhibidores de KRAS G12c y métodos de uso de los mismos
US20190375749A1 (en)	2018-06-11	2019-12-12	Amgen Inc.	Kras g12c inhibitors and methods of using the same
CN112040945A (zh)	2018-06-12	2020-12-04	Vtv治疗有限责任公司	葡萄糖激酶激活剂与胰岛素或胰岛素类似物组合的治疗用途
ES3060664T3 (en)	2018-06-12	2026-03-27	Amgen Inc	Kras g12c inhibitors encompassing a piperazine ring and use thereof in the treatment of cancer
MX2021000977A (es)	2018-07-26	2021-04-12	Sumitomo Pharma Oncology Inc	Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos.
JP7516029B2 (ja)	2018-11-16	2024-07-16	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法
US11053226B2 (en)	2018-11-19	2021-07-06	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
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
US11034710B2 (en)	2018-12-04	2021-06-15	Sumitomo Dainippon Pharma Oncology, Inc.	CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
WO2020132045A1 (en)	2018-12-19	2020-06-25	Disarm Therapeutics, Inc.	Inhibitors of sarm1 in combination with neuroprotective agents
EP3898616B1 (en)	2018-12-20	2024-10-02	Amgen Inc.	Heteroaryl amides useful as kif18a inhibitors
WO2020132651A1 (en)	2018-12-20	2020-06-25	Amgen Inc.	Kif18a inhibitors
TWI844602B (zh)	2018-12-20	2024-06-11	美商安進公司	Kif18a抑制劑
JP7676308B2 (ja)	2018-12-20	2025-05-14	アムジエン・インコーポレーテツド	Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド
NZ778055A (en)	2019-02-12	2025-11-28	Sumitomo Pharma America Inc	Formulations comprising heterocyclic protein kinase inhibitors
WO2020180768A1 (en)	2019-03-01	2020-09-10	Revolution Medicines, Inc.	Bicyclic heteroaryl compounds and uses thereof
CN113727758A (zh)	2019-03-01	2021-11-30	锐新医药公司	双环杂环基化合物及其用途
US11793802B2 (en)	2019-03-20	2023-10-24	Sumitomo Pharma Oncology, Inc.	Treatment of acute myeloid leukemia (AML) with venetoclax failure
CA3133460A1 (en)	2019-03-22	2020-10-01	Sumitomo Dainippon Pharma Oncology, Inc.	Compositions comprising pkm2 modulators and methods of treatment using the same
EP3738593A1 (en)	2019-05-14	2020-11-18	Amgen, Inc	Dosing of kras inhibitor for treatment of cancers
NZ782284A (en)	2019-05-21	2024-11-29	Amgen Inc	Solid state forms
WO2021026099A1 (en)	2019-08-02	2021-02-11	Amgen Inc.	Kif18a inhibitors
AU2020326627B2 (en)	2019-08-02	2026-01-29	Amgen Inc.	KIF18A inhibitors
EP4007756B1 (en)	2019-08-02	2025-12-24	Amgen Inc.	Kif18a inhibitors
US12540129B2 (en)	2019-08-02	2026-02-03	Amgen Inc.	KIF18A inhibitors
EP4684786A3 (en)	2019-10-24	2026-04-08	Amgen Inc.	Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer
WO2021091956A1 (en)	2019-11-04	2021-05-14	Revolution Medicines, Inc.	Ras inhibitors
MX2022005359A (es)	2019-11-04	2022-06-02	Revolution Medicines Inc	Inhibidores de ras.
CN120699039A (zh)	2019-11-04	2025-09-26	锐新医药公司	Ras抑制剂
TW202128688A (zh)	2019-11-08	2021-08-01	美商銳新醫藥公司	雙環雜芳基化合物及其用途
JP2023501528A (ja)	2019-11-14	2023-01-18	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の改善された合成
WO2021097207A1 (en)	2019-11-14	2021-05-20	Amgen Inc.	Improved synthesis of kras g12c inhibitor compound
EP4065231A1 (en)	2019-11-27	2022-10-05	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
CN114929279A (zh)	2020-01-07	2022-08-19	锐新医药公司	Shp2抑制剂给药和治疗癌症的方法
WO2021155006A1 (en)	2020-01-31	2021-08-05	Les Laboratoires Servier Sas	Inhibitors of cyclin-dependent kinases and uses thereof
US12391658B2 (en)	2020-02-18	2025-08-19	Vtv Therapeutics Llc	Sulfoxide and sulfone glucokinase activators and methods of use thereof
MX2023002248A (es)	2020-09-03	2023-05-16	Revolution Medicines Inc	Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2.
MX2023003060A (es)	2020-09-15	2023-04-05	Revolution Medicines Inc	Derivados indolicos como inhibidores de ras en el tratamiento del cancer.
US20240051956A1 (en)	2020-12-22	2024-02-15	Qilu Regor Therapeutics Inc.	Sos1 inhibitors and uses thereof
AU2022268962A1 (en)	2021-05-05	2023-12-14	Revolution Medicines, Inc.	Ras inhibitors for the treatment of cancer
CA3217393A1 (en)	2021-05-05	2022-11-10	Elena S. Koltun	Ras inhibitors
WO2022235866A1 (en)	2021-05-05	2022-11-10	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
AR127308A1 (es)	2021-10-08	2024-01-10	Revolution Medicines Inc	Inhibidores ras
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
WO2023172858A1 (en)	2022-03-07	2023-09-14	Amgen Inc.	A process for preparing 4-methyl-2-propan-2-yl-pyridine-3-carbonitrile
CN119136806A (zh)	2022-03-08	2024-12-13	锐新医药公司	用于治疗免疫难治性肺癌的方法
WO2023240263A1 (en)	2022-06-10	2023-12-14	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
AU2023358792A1 (en)	2022-10-14	2025-04-17	Black Diamond Therapeutics, Inc.	Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives
AU2023416218A1 (en) *	2022-12-28	2025-07-10	Beyang Therapeutics Co., Ltd.	Protein tyrosine kinase inhibitor and medical use thereof
EP4687905A1 (en)	2023-03-30	2026-02-11	Revolution Medicines, Inc.	Compositions for inducing ras gtp hydrolysis and uses thereof
KR20260005904A (ko)	2023-04-07	2026-01-12	레볼루션 메디슨즈, 인크.	매크로사이클릭 ras 억제제
CN121263418A (zh)	2023-04-07	2026-01-02	锐新医药公司	大环ras抑制剂
AU2024252105A1 (en)	2023-04-14	2025-10-16	Revolution Medicines, Inc.	Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
KR20250172857A (ko)	2023-04-14	2025-12-09	레볼루션 메디슨즈, 인크.	Ras 억제제의 결정형
AU2024265078A1 (en)	2023-05-04	2025-12-11	Revolution Medicines, Inc.	Combination therapy for a ras related disease or disorder
IL326136A (en)	2023-08-07	2026-03-01	Revolution Medicines Inc	RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein
US20250154171A1 (en)	2023-10-12	2025-05-15	Revolution Medicines, Inc.	Ras inhibitors
TW202542151A (zh)	2023-12-22	2025-11-01	美商銳格醫藥有限公司	Ｓｏｓ１抑制劑及其用途
WO2025171296A1 (en)	2024-02-09	2025-08-14	Revolution Medicines, Inc.	Ras inhibitors
WO2025240847A1 (en)	2024-05-17	2025-11-20	Revolution Medicines, Inc.	Ras inhibitors
US20250375445A1 (en)	2024-06-07	2025-12-11	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en)	2024-06-21	2025-12-26	Revolution Medicines, Inc.	Therapeutic compositions and methods for managing treatment-related effects
WO2026002137A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂游离碱的晶型
WO2026002126A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂及其眼用制剂
WO2026002142A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂的半琥珀酸盐晶型
WO2026002133A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂的盐型
WO2026006747A1 (en)	2024-06-28	2026-01-02	Revolution Medicines, Inc.	Ras inhibitors
WO2026015796A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015801A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015825A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Use of ras inhibitor for treating pancreatic cancer
WO2026015790A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026050446A1 (en)	2024-08-29	2026-03-05	Revolution Medicines, Inc.	Ras inhibitors
WO2026072904A2 (en)	2024-09-26	2026-04-02	Revolution Medicines, Inc.	Compositions and methods for treating lung cancer

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4059433A (en) *	1976-06-18	1977-11-22	Fmc Corporation	3-Alkoxyisothiazole derivatives as herbicides
US4057416A (en) *	1976-06-18	1977-11-08	Fmc Corporation	3-Alkylthio-, 3-alkylsulfinyl-, and 3-alkylsulfonylisothiazole derivatives as herbicides
US5409930A (en)	1991-05-10	1995-04-25	Rhone-Poulenc Rorer Pharmaceuticals Inc.	Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
MY109202A (en)	1992-07-10	1996-12-31	Nihon Nohyaku Co Ltd	Isothiazole derivatives and processes for preparing the same as well as termite controlling agents comprising the same as active ingredient
US6177401B1 (en) *	1992-11-13	2001-01-23	Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften	Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis
IL112721A0 (en)	1994-03-10	1995-05-26	Zeneca Ltd	Azole derivatives
DE4425642A1 (de) *	1994-07-20	1996-01-25	Merck Patent Gmbh	Partiell fluorierte Benzolderivate
NZ503788A (en)	1997-10-27	2002-11-26	Agouron Pharma	4-aminothiazole derivatives and their use as inhibitors of cyclin-dependent kinases
UA60365C2 (uk) *	1998-06-04	2003-10-15	Пфайзер Продактс Інк.	Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця
CZ20031315A3 (cs) *	2000-11-28	2004-04-14	Pfizer Products Inc.	Soli isothiazolkarboxamidu a jejich použití jako prostředků proti hyperproliferaci
CA2513140A1 (en) *	2003-01-27	2004-08-12	Pfizer Products Inc.	Isothiazole derivatives

1999
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- 1999-05-03 EP EP99914724A patent/EP1084114B1/en not_active Expired - Lifetime
- 1999-05-03 DE DE69920009T patent/DE69920009T2/de not_active Expired - Lifetime
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2000
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2001
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2003
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2004
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Publication number	Publication date
US20030149048A1 (en)	2003-08-07
AP1309A (en)	2004-09-14
CA2475113A1 (en)	1999-12-09
NZ507009A (en)	2003-11-28
US7790902B2 (en)	2010-09-07
IS2269B (is)	2007-07-15
CO5011121A1 (es)	2001-02-28
CN1303380A (zh)	2001-07-11
ID27006A (id)	2001-02-22
UY25619A1 (es)	2000-02-23
BR9910900B1 (pt)	2013-09-17
KR20010052516A (ko)	2001-06-25
US6548526B2 (en)	2003-04-15
PT1084114E (pt)	2004-12-31
ZA993752B (en)	2000-12-04
US20010020034A1 (en)	2001-09-06
GT199900070A (es)	2000-11-10
ATE275553T1 (de)	2004-09-15
ES2226368T3 (es)	2005-03-16
DE69920009D1 (de)	2004-10-14
CZ298559B6 (cs)	2007-11-07
AU3342199A (en)	1999-12-20
AR016725A1 (es)	2001-07-25
PE20000568A1 (es)	2000-07-08
TNSN99106A1 (fr)	2005-11-10
SK17782000A3 (sk)	2001-08-06
CA2333703C (en)	2005-06-14
EP1084114B1 (en)	2004-09-08
EA200001146A1 (ru)	2001-04-23
EP1084114A1 (en)	2001-03-21
HUP0102422A3 (en)	2002-06-28
JP2002517384A (ja)	2002-06-18
BG65104B1 (bg)	2007-02-28
PL344691A1 (en)	2001-11-19
MA26638A1 (fr)	2004-12-20
JP3735254B2 (ja)	2006-01-18
NO20006071L (no)	2000-11-30
GEP20084337B (2)	2008-03-25
UA60365C2 (uk)	2003-10-15
BR9910900A (pt)	2001-02-13
US20080300249A1 (en)	2008-12-04
OA11504A (en)	2004-05-17
HRP20000835A2 (en)	2001-12-31
BG104998A (en)	2001-07-31
SK286405B6 (sk)	2008-09-05
US6235764B1 (en)	2001-05-22
AP9901560A0 (en)	1999-06-30
NO20006071D0 (no)	2000-11-30
CZ20004451A3 (en)	2001-05-16
SI1084114T1 (en)	2005-02-28
EA004935B1 (ru)	2004-10-28
PL198151B1 (pl)	2008-05-30
HK1036982A1 (en)	2002-01-25
KR100392434B1 (ko)	2003-07-22
US7405218B2 (en)	2008-07-29
CN1172918C (zh)	2004-10-27
MY130668A (en)	2007-07-31
YU70100A (sh)	2004-07-15
CA2475113C (en)	2008-03-18
DE69920009T2 (de)	2005-09-15
WO1999062890A1 (en)	1999-12-09
NO318798B1 (no)	2005-05-09
PA8472301A1 (es)	2000-09-29
HN1999000080A (es)	1999-09-29
HRP20000835B1 (hr)	2008-01-31
TR200003478T2 (tr)	2001-03-21
HUP0102422A2 (hu)	2002-05-29
IL138776A0 (en)	2001-10-31
JP2005002122A (ja)	2005-01-06
CN1616386A (zh)	2005-05-18
IS5690A (is)	2000-10-27
SA99200217B1 (ar)	2006-05-06
CA2333703A1 (en)	1999-12-09

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