BR112012008094A2 - derivado de aminopirazol, seu uso, composição farmacêutica que o compreende, agentes para inibir a atividade de fgfr e para prevenir ou tratar câncer - Google Patents
derivado de aminopirazol, seu uso, composição farmacêutica que o compreende, agentes para inibir a atividade de fgfr e para prevenir ou tratar câncer Download PDFInfo
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- BR112012008094A2 BR112012008094A2 BR112012008094-6A BR112012008094A BR112012008094A2 BR 112012008094 A2 BR112012008094 A2 BR 112012008094A2 BR 112012008094 A BR112012008094 A BR 112012008094A BR 112012008094 A2 BR112012008094 A2 BR 112012008094A2
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- Prior art keywords
- alkyl
- aryl
- group
- membered
- haloalkyl
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 19
- 201000011510 cancer Diseases 0.000 title claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 4
- 230000000694 effects Effects 0.000 title abstract description 4
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 title description 2
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract 74
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 34
- 125000003118 aryl group Chemical group 0.000 claims abstract 27
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims abstract 21
- 150000001875 compounds Chemical class 0.000 claims abstract 12
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 11
- 150000003839 salts Chemical class 0.000 claims abstract 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 24
- 229910052739 hydrogen Inorganic materials 0.000 claims 16
- 239000001257 hydrogen Substances 0.000 claims 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 16
- 125000003342 alkenyl group Chemical group 0.000 claims 12
- 125000000304 alkynyl group Chemical group 0.000 claims 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims 11
- 125000003545 alkoxy group Chemical group 0.000 claims 10
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 150000002367 halogens Chemical group 0.000 claims 7
- -1 cyan Chemical group 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 229940049920 malate Drugs 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- 229940095064 tartrate Drugs 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 108091008794 FGF receptors Proteins 0.000 abstract description 9
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 abstract description 5
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 2
- 102000020233 phosphotransferase Human genes 0.000 abstract description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 4
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- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
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- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
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- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
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- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
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- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
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- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
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- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
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- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
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- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
Classifications
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- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
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- C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C—CHEMISTRY; METALLURGY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
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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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Abstract
DERIVADO DE AMINOPIRAZOL, SEU USO, COMPOSIÇÃO FARMACÊUTICA QUE O COMPREENDE, AGENTES PARA INIBIR A ATIVIDADE DE FGFR E PARA PREVENIR OU TRATAR CÂNCER
A presente invenção refere-se a um composto representado pela fórmula (I)
(I)
ou um sal farmacologicamente aceitável do mesmo, que pode inibir uma cinase da família de receptor de fator de crescimento de fibroblasto (FGFR) em tecidos de câncer. (Na fórmula, A representa um grupo heteroarila de 5 a 10 membros, ou um grupo C 6-10 arila; R1 e R2 independentemente representam H, OH, X, CN, N02, um grupo C1-4 haloalquila, um grupo C1-6 alquila, ou similares <r1 e="" r2="" juntos="" formam="" uma="" heterociclila="" (substituída)="" de="" 3="" a="" 10="" membros="" grupo="" ou="" heteroarila="" 5="">; R3 representa H, um grupo C1-5 alquila, um grupo C6-10 arila, um grupo C1-5 alquila, ou um grupo C1-4 haloalquila; e R4 representa H, X, um grupo C1- 3 alquila, um grupo C1-4 haloalquila, OH, CN, N02, ou similares.). </r1>
Description
: 1/314 Relatório Descritivo da Patente de Invenção para "DERIVADO DE AMINOPIRAZOL, SEU USO, COMPOSIÇÃO FARMACÊUTICA QUE O - COMPREENDE, AGENTES PARA INIBIR A ATIVIDADE DE FGFR E PARA PREVENIR OU TRATAR CÂNCER". ' 5 Campo Técnico A presente invenção refere-se a derivados de aminopirazol e u- sos dos mesmos.
Antecedentes da Invenção A maioria dos atualmente promissores fármacos molecularmente —alvejados contra o câncer são inibidores de tirosina cinase receptora tais como erlotinib e lapatinib.
Muitos deles são altamente eficazes contra cânceres com mutação, amplificação, ou superexpressão de genes alvo.
Entretanto, tais a- gentes alvos moleculares não podem exercer eficácia contra cânceres em que genes que não são seus alvos são alterados.
Desse modo, não existe ainda nenhum método terapêutico estabelecido que seja eficaz contra tais cânceres.
Inibidores contra novos genes alterados em câncer são supostos dar uma grande contribuição para o tratamento de pacientes de câncer sobre os quais os fármacos convencionais não possuem nenhum efeito.
Receptores de fator de crescimento de fibroblasto (FGFRs) são ci- —nases que pertencem à família de tirosina cinase receptora.
FGFR1, FGFR2, FGFR3, e FGFRA4 constituem a família FGFR.
O ligante é fator de crescimento de fibroblasto (FGF), e 22 tipos de proteínas estruturalmente similares formam a família.
Sabe-se que cada FGFR é ativado em superexpressão, amplificação de gene, mutação, ou translocação, e serve como uma causa de câncer.
O sinal de FGFR segue a trilha de MAPK ou trilha de PISK/YAKT.
Em câncer, o sinal é conhecido estar envolvido em crescimento celular, angiogênese, migra- ção celular, invasão, metástase, e tais (Documento de não patente 1). O gene FGFR1 é conhecido ser amplificado em câncer de mama e câncer de pulmão de célula não pequena (Documentos de Não-patente 2 e 3); mutadoem glioblastoma (Documento de não patente 4); translocado para gerar uma proteína de fusão em leucemia mielocítica aguda (Documento de
Claims (11)
1. Composto, caracterizado pelo fato de que é representado pela seguinte fórmula geral (I), ou um sal farmaceuticamente aceitável do mesmo: R24Y A di, o | E | Xe. NH, R1 T
N NA ON [ [| Sra
RN R4 à (1) em que R1, R2, Ra, e Ra cada independentemente representa o grupolistado abaixo: R1 representa hidrogênio, hidróxi, halogênio, ciano, nitro, C14 ha- loalquila, C1.6 alquila, Ca.6 alquenila, Ca.6 alquinila, Ca; cicloalquila, Ce19 aril C14 alguila, -OR5, -NReR7, -(CRgR9)nZ1, -C(OINR1i2R13, -SRi, -SOR15, - SO2R16, -NR17SO2R18, COOH, Ce-109 arila que é opcionalmente substituído porum ou mais grupos independentemente selecionados de grupo P, hete- roarila de 5 a 10 membros ou heterociclila de 3 a 10 membros que é opcio- nalmente substituído por um ou mais grupos independentemente seleciona- dos do grupo Q, -COR19, -COOR29, -OC(O)R21, -NR22C(O)R23, -NR24C(S)Roa5, “C(S)NR26R27, -SO2NR28R29, -OSO2R30, -SO3R31, ou -Si(R32)3; R2 representa hidrogênio, hidróxi, halogênio, ciano, nitro, C14 ha- loalquila, C1.6 alquila, Ca.6 alquenila, Ca.6 alquinila, Ca; cicloalquila, Ce19 aril C14 alquila, -OR5, -NReR7, -(CRR9)nZ1, -C(OINR12R13, -SRia4, -SOR15, - SO2R16, -NR17SO2R18, COOH, Cge-10 arila que é opcionalmente substituído por um ou mais grupos independentemente selecionados de grupo P, hete- roarilade 5 a 10 membros ou heterociclila de 3 a 10 membros que é opcio- nalmente substituído por um ou mais grupos independentemente seleciona- dos do grupo Q, -COR19, -COOR20, -OC(O)R21, -NR22C(O)R23, -NR24C(S)Ras, -C(S)INR26R27, -SO2NR28R29, -OSO2R30, -SO3R31, ou -Si(R32)3; ou R1 e R2, juntamente com um átomo ligado a eles, formam hete- rociclla de 3 a 10 membros ou heteroarila de 5 a 10 membros, em que a heterociclila ou heteroarila é opcionalmente substituída por halogênio;
R3 representa hidrogênio, C1.5 alquila, Ce10 aril Cie alquila, ou C14 haloalquila;
Ra representa hidrogênio, halogênio, C1.3 alquila, C1-3 perfluoro- alquila, ciano, metanossulfonila, hidroxila, alcóxi ou amino;
Arepresenta um indol ou pirrol;
Rs representa C1.5 alquila, Ca-7 cicloalquila, C3-7 cicloalquila C1.3 alquila, Ca. alquenila, Ca.6 alquinila, Cia haloalquila, C1.3 alcóxi C1.4 alquila, C13 alcóxi C14 alcóxi C14 alquila, Cia aminoalquila, C14 alquilamino C14 al- quila, di(C14 alquil)amino C1.4 alquila, Ce-109 arila, Ce-10 aril C1.3 alquila, ou he-
terociclila C1.3 alquila de 3 a 10 membros, heterociclila de 3 a 10 membros, heteroarila de 5 a 10 membros, heteroarila de 5 a 10 membros C1.3 alquila, C1-.6 mono-hidróxi alquila, C1.6 di-hidróxi alquila, ou C1+ tri-hidróxi alguila que é opcionalmente substituído por um ou mais grupos independentemente se- lecionados do grupo Q;
Rs: e R7, que são iguais ou diferentes, cada qual representa hi- drogênio, C1.4 alquila, C2.6 alquenila, C2.6 alquinila, C1.4 haloalquila, C1.3 alcó- xi C1.4 alquila, Ce 109 aril C1.3 alquila, heterociclila C1.3 alguila de 3 a 10 mem- bros, heteroarila de 5 a 10 membros C13 alquila, Ci. mono-hidróxi alquila, C1-6 di-hidróxi alquila, C1.6 tri-hidróxi alquila, heterociclila de 3 a 10 membros,
Cia aminoalquila, Ci, alquilamino C14 alquila, di(C14 alquil)amino C1.4 alqui- la, ou ciano(C1-3 alquila); ou Rg e R7, juntamente com um átomo de nitrogê- nio ligado a eles, formam heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros;
n representa 1 a 3;
Rg e Ro, que são iguais ou diferentes, cada qual representa hi- drogênio, C14 alquila, ou halogênio; ou alternativamente, Rg e Ra, juntamen- te com um átomo de carbono ligado a eles, formam um anel cicloalifático;
Z, representa hidrogênio, NR1oR11, -OH, ou heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros que é opcionalmente substi-
tuído por um ou mais grupos independentemente selecionados do grupo Q;
Ra1o e Ru, que são iguais ou diferentes, cada qual representa C1.- 4 alquila, Ca.6 alquenila, C2.6 alquinila, C1.4 haloalquila, C1.3 alcóxi C14 alquila,
ciano(C13 alquila), ou C13 alquilsulfonila Cia alquila; ou alternativamente, Rio e Ru, juntamente com um átomo de nitrogênio ligado a eles, formam heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros; R12 € R13, que são iguais ou diferentes, cada qual representa hi- drogênio, Ci, alquila, C2.6 alquenila, C2.6 alquinila, C1.4 haloalquila, C1.3 alcó- xi C14 alquila, Ce-10 arila, heteroarila de 5 a 10 membros, heterociclila de 3 a membros, Ce-10 aril Cia alquila, heterociclila C1-3 alguila de 3 a 10 mem- bros, heteroarila de 5 a 10 membros C1.3 alquila, ciano(C1.3 alquila), C13 al- quilsulfonila C14 alquila, anel cicloalifático de 3 a 10 membros, heteroarila de
10 5a10 membros, ou heterociíclila de 3 a 10 membros; ou alternativamente, R12 e R13, juntamente com um átomo de nitrogênio ligado a eles, formam heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros que é opcionalmente substituído por um ou mais grupos independentemente sele- cionados do grupo Q;
Ra1a representa Ci, alquila, C2.6 alguenila, Ca.6 alquinila, C1.4 ha- loalquila, Ce.109 arila que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo P, ou heteroarila de 5 a 10 mem- bros ou heterociclila de 3 a 10 membros que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo Q;
R15 representa C1,4 alquila, Ca.6 alqguenila, Ca.6 alquinila, C14 ha- loalquila, Ceg-19 arila que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo P, ou heteroarila de 5 a 10 mem- bros ou heterociclila de 3 a 10 membros que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo Q;
Ra16 representa C1., alquila, C2.6 alqguenila, C2.6 alquinila, C1.4 ha- loalquila, Ce.10 arila que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo P, ou heteroarila de 5 a 10 mem- bros ou heterociclila de 3 a 10 membros que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo Q;
R17 representa hidrogênio ou C14 alquila;
R13 representa C1., alquila, C2.6 alqguenila, C2.6 alquinila, C1.4 ha- loalquila, Ce.109 arila que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo P, ou heteroarila de 5 a 10 mem- bros ou heterociclila de 3 a 10 membros que é opcionalmente substituído por um ou mais grupos independentemente selecionados do grupo Q; R19 representa hidrogênio, C1.4 alquila, Ca.; cicloalquila, C1.4 ha- loalquila, Ce.109 arila, ou heteroarila de 5 a 10 membros ou heterociclila de 3 a membros que é opcionalmente substituído por um ou mais grupos inde- pendentemente selecionados do grupo Q; R2o representa C1.4 alquila, Ca,7 cicloalquila, C14 haloalquila, Ce. 10 arila, heteroarila de 5 a 10 membros, ou heterociclila de 3 a 10 membros; 10 R2, representa C1.4 alquila, C3.7 cicloalquila, C14 haloalquila, Ce- 10 arila, heteroarila de 5 a 10 membros, ou heterociclila de 3 a 10 membros; R22 representa hidrogênio, C14 alquila, ou C1.4 haloalquila; R>23 representa hidrogênio, C1.4 alquila, C3.7 cicloalquila, C1.4 ha- loalquila, Ce.105 arila, heteroarila de 5 a 10 membros, ou heterocíclila de 3 a 10membros; R24 representa hidrogênio, C14 alquila, ou C1.4 haloalquila; R25 representa C1.4 alquila, Ca,7 cicloalquila, C14 haloalquila, Ce. 10 arila, heteroarila de 5 a 10 membros, ou heterociclila de 3 a 10 membros; R26 € R27, que são iguais ou diferentes, cada qual representa hi- drogênio, Ci alquila, Ca.6 alquenila, Ca.6 alquinila, C14 haloalquila, C13 alco- xila C14 alquila, Ce-109 arila, heteroarila de 5 a 10 membros, heterociclila de 3 a 10 membros, Cçe.10 aril C1.4 alquila, heterociclila C1.3 alguila de 3 a 10 mem- bros, heteroarila de 5 a 10 membros C1-3 alquila, ciano(C1-3 alquila), C1-3 al- quilsulfonila C14 alquila, ou anel cicloalifático de 3 a 10 membros; ou alterna- tivamente, Rax6 e R27, juntamente com um átomo de nitrogênio ligado a eles, formam heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros; R28 E R29, que são iguais ou diferentes, cada qual representa hi- drogênio, C14 alquila, C2.6 alquenila, Ca.6 alquinila, C14 haloalquila, C1.3 alco- xila C14 alquila, Ce-10 arila, heteroarila de 5 a 10 membros, heterociclila de 3 a10membros, Ce.10 aril C1.4 alquila, heterociclila C1.3 alquila de 3 a 10 mem- bros, heteroarila de 5 a 10 membros C1.3 alquila, ciano(C1.3 alquila), C1.3 al- quilsulfonila C14 alquila, ou anel cicloalifático de 3 a 10 membros; ou alterna-
tivamente, R28 e R29, juntamente com um átomo de nitrogênio ligado a eles, formam heterociclila de 3 a 10 membros ou heteroarila de 5 a 10 membros; R3o representa C1.4 alquila, C3.7 cicloalquila, C14 haloalquila, Ce 10 arila, heteroarila de 5 a 10 membros, ou heterociclila de 3 a 10 membros; R31 representa C14 alquila, C3.7 cicloalquila, C1.4 haloalquila, Ce-10 arila, heteroarila de 5 a 10 membros, ou heterociclila de 3 a 10 membros; R32 representa C14 alquila ou Cçe.10 arila; <grupo P> halogênio, C1.4 alquila, C14 haloalquila, -OH, C1-3 alcóxi, C1.3 ha- loalcóxi, heterociclilamino de 3 a 10 membros, -SO2R16, -CN, -NO;, e hetero- ciclila de 3 a 10 membros; <grupo Q> halogênio, Cia alquila, Ci, haloalquila, -OH, C1.3 alcóxi, Ci-6 mono-hidróxi alquila, C1.6 di-hidróxi alquila, C1.6 tri-hidróxi alquila, heterociclil amina de 3 a 10 membros, -SO2R16, -CN, -NO>, C3-7 cicloalquila, -COR 19, e heterociclila de 3 a 10 membros que é opcionalmente substituído por Ci alquila, com a condição de que o referido composto representado pela fórmula geral (1) exclua o [5-amino-1-(2-metil-1H-benzimidazo|-5-1)-1H- pirazol-4-iI)-[5-(4-trifluorometil-fenil)-1H-indol-2-il]-metanona; e em que a cicloalquila se refira a um grupo hidrocarboneto alifáti- co monovalente cíclico saturado ou parcialmente saturado.
2. Composto de acordo com a reivindicação 1, ou um sal farma- ceuticamente aceitável do mesmo, caracterizado pelo fato de que R;3 repre- senta hidrogênio, C1.4 alquila, Ce.109 aril C14 alquila, ou C1.3 perfluoroalquila.
3. Composto de acordo com a reivindicação 1 ou 2, ou um sal farmaceuticamente aceitável do mesmo, caracterizado pelo fato de que é representado pela seguinte fórmula:
CA N P & NAN
SW TU
4. Composto, caracterizado pelo fato de que é selecionado do grupo que consiste em: [5-amino-1-(2-metil-3H-benzimidazo]-5-il)-1H-pirazol-4-i1]-(1H- indol-2-il)-netanona L-malato; cloridrato de [5-amino-1-(2-metil-1 H-benzimidazo|-5-i1)-1H- pirazol-4-i1]-(1H-indol-2-il)-netanona; e [5-amino-1-(2-metil-1 H-benzimidazol-5-il)-1 H-pirazol-4-11)-(1H- indol-2-il)-metanona 1-metanossulfonato monoidratado.
5. Composto de acordo com qualquer uma das reivindicações 1 a3,ouum sal farmaceuticamente aceitável do mesmo, caracterizado pelo fato de que o sal farmaceuticamente aceitável é selecionado do grupo con- sistindo em acetato, succinato, fumarato, maleato, tartarato, citrato, lactato, malato, estearato, benzoato, metanossulfonato e p-toluenossulfonato.
6. Composição farmacêutica, caracterizada pelo fato de que compreende o composto, como definido em qualquer uma das reivindica- ções 1 a 5, ou um sal farmaceuticamente aceitável do mesmo; e um veículo.
7. Agente para uso em um método para prevenir ou tratar cân- cer, caracterizado pelo fato de que compreende como um ingrediente ativo o composto, como definido em qualquer uma das reivindicações 1 a 5, ou um —salfarmaceuticamente aceitável do mesmo.
8. Agente para uso em um método para prevenir ou tratar câncer de acordo com a reivindicação 7, caracterizado pelo fato de que o câncer é pelo menos um selecionado do grupo que consiste em: câncer de mama, leucemia mielocítica aguda, câncer pancreáti- co, câncer de bexiga, câncer prostático, câncer esofágico, angiogênese, câncer de estômago, câncer do corpo uterino, câncer ovariano, tumor cere- bral, câncer de cólon, mieloma múltiplo, hepatocarcinoma, câncer pulmonar, e câncer de tireoide.
9. Composição, caracterizada pelo fato de que compreende o composto, como definido em qualquer uma das reivindicações 1 a 5, ou um sal farmaceuticamente aceitável do mesmo para uso em um método para prevenir ou tratar câncer, compreendendo administrar uma quantidade far-
maceuticamente eficaz da dita composição a um paciente em necessidade de prevenção ou tratamento de câncer.
10. Uso do composto, como definido em qualquer uma das rei- vindicações 1 a 5, ou um sal farmaceuticamente aceitável do mesmo, carac- terizado pelo fato de ser na produção de um agente para prevenir ou tratar câncer.
11. Composto de acordo com qualquer uma das reivindicações 1 a 5, ou um sal farmaceuticamente aceitável do mesmo, caracterizado pelo fato de ser para uso em um método para prevenção ou tratamento de cân- cer
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PCT/JP2010/063315 WO2011016528A1 (ja) | 2009-08-07 | 2010-08-05 | アミノピラゾール誘導体 |
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Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK2471786T3 (en) | 2009-08-07 | 2016-01-25 | Chugai Pharmaceutical Co Ltd | aminopyrazole derivative |
US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
JP5963222B2 (ja) * | 2012-02-20 | 2016-08-03 | ローディア オペレーションズ | Dfmb誘導体の製造方法 |
PT3176170T (pt) | 2012-06-13 | 2019-02-05 | Incyte Holdings Corp | Compostos tricíclicos substituídos como inibidores de fgfr |
ES2916220T3 (es) | 2012-07-11 | 2022-06-29 | Blueprint Medicines Corp | Inhibidores del receptor de factor de crecimiento de fibroblasto |
WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
EP2902489B9 (en) * | 2012-09-27 | 2018-02-07 | Chugai Seiyaku Kabushiki Kaisha | Fgfr3 fusion gene and pharmaceutical drug targeting same |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
AR094812A1 (es) | 2013-02-20 | 2015-08-26 | Eisai R&D Man Co Ltd | Derivado de piridina monocíclico como inhibidor del fgfr |
SG10201708520YA (en) | 2013-04-19 | 2017-12-28 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
CN103224479B (zh) * | 2013-04-26 | 2014-10-15 | 温州大学 | 一种2-芳基苯并呋喃类化合物的合成方法 |
KR20160035003A (ko) * | 2013-07-31 | 2016-03-30 | 추가이 세이야쿠 가부시키가이샤 | 아미노피라졸 유도체 함유 의약품 제제 |
ES2924111T3 (es) | 2013-10-25 | 2022-10-04 | Blueprint Medicines Corp | Inhibidores del receptor del factor de crecimiento de fibroblastos |
MX2016006351A (es) * | 2013-12-13 | 2016-08-01 | Hoffmann La Roche | Inhibidores de tirosina cinasa de bruton. |
RU2648236C2 (ru) * | 2013-12-13 | 2018-03-23 | Ф. Хоффманн-Ля Рош Аг | Ингибиторы тирозинкиназы брутона |
EP3080097B1 (en) | 2013-12-13 | 2018-04-18 | F.Hoffmann-La Roche Ag | Inhibitors of bruton's tyrosine kinase |
US10391081B2 (en) | 2013-12-27 | 2019-08-27 | Chugai Seiyaku Kabushiki Kaisha | FGFR gatekeeper mutant gene and drug targeting same |
US9695165B2 (en) | 2014-01-15 | 2017-07-04 | Blueprint Medicines Corporation | Inhibitors of the fibroblast growth factor receptor |
CN106459993A (zh) | 2014-03-31 | 2017-02-22 | 德彪药业国际股份公司 | Fgfr融合体 |
AU2015286049B2 (en) * | 2014-07-08 | 2018-03-01 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic derivatives and pharmaceutical applications thereof |
MX369646B (es) | 2014-08-18 | 2019-11-15 | Eisai R&D Man Co Ltd | Sal de derivado de piridina monociclico y su cristal. |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
TWI712601B (zh) | 2015-02-20 | 2020-12-11 | 美商英塞特公司 | 作為fgfr抑制劑之雙環雜環 |
WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
EP3312172B1 (en) | 2015-06-17 | 2020-05-06 | Chugai Seiyaku Kabushiki Kaisha | Aminopyrazole derivatives useful as src kinase inhibitors |
WO2017017516A1 (en) | 2015-07-24 | 2017-02-02 | Debiopharm International Sa | Fgfr expression and susceptibility to an fgfr inhibitor |
JP6549311B2 (ja) * | 2015-08-20 | 2019-07-24 | 浙江海正薬業股▲ふん▼有限公司Zhejiang Hisun Pharmaceutical CO.,LTD. | インドール誘導体、その調製方法および医薬におけるその使用 |
WO2017157332A1 (zh) * | 2016-03-18 | 2017-09-21 | 江苏恒瑞医药股份有限公司 | 芳香酰胺类衍生物、其制备方法及其在医药上的应用 |
CN110022900A (zh) | 2016-09-08 | 2019-07-16 | 蓝图药品公司 | 成纤维细胞生长因子受体4抑制剂与细胞周期蛋白依赖性激酶抑制剂的组合 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
JPWO2019189241A1 (ja) | 2018-03-28 | 2021-03-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 肝細胞癌治療剤 |
MA52493A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Sels d'un inhibiteur de fgfr |
US11466004B2 (en) | 2018-05-04 | 2022-10-11 | Incyte Corporation | Solid forms of an FGFR inhibitor and processes for preparing the same |
CN110950848B (zh) * | 2018-09-27 | 2024-03-26 | 徐诺药业 | 新型氨基吡唑类衍生物的合成与应用 |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
CN110092791B (zh) * | 2019-05-17 | 2020-04-03 | 河南大学 | 5,6-吲哚并二恶烷类衍生物及其制备方法和应用 |
US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN112358435B (zh) * | 2019-10-12 | 2023-01-10 | 中国医学科学院医药生物技术研究所 | 取代芳并杂环类化合物、制备方法和抑制ulk1及抗肿瘤用途 |
CA3157361A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
TW202333686A (zh) * | 2021-12-08 | 2023-09-01 | 美商奇奈特生物製藥公司 | 以fgfr激酶抑制劑治療癌症 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR0170567B1 (ko) | 1992-12-17 | 1999-02-18 | 알렌 제이. 스피겔 | 부신피질자극호르몬-유리 인자 길항물질 활성을 갖는 피라졸 및 피라졸로피리미딘 |
US6316466B1 (en) * | 1998-05-05 | 2001-11-13 | Syntex (U.S.A.) Llc | Pyrazole derivatives P-38 MAP kinase inhibitors |
JP3590586B2 (ja) | 1998-05-05 | 2004-11-17 | エフ.ホフマン−ラ ロシュ アーゲー | P−38mapキナーゼインヒビターとしてのピラゾール誘導体 |
AU6762400A (en) * | 1999-08-12 | 2001-03-13 | Cor Therapeutics, Inc. | Inhibitors of factor xa |
JP2003050945A (ja) | 2001-08-06 | 2003-02-21 | Takashi Hashimoto | 連動型広告配信システム及び広告配信サーバの動作方法 |
FR2831537B1 (fr) * | 2001-10-26 | 2008-02-29 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation |
JP5039268B2 (ja) | 2001-10-26 | 2012-10-03 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | ベンゾイミダゾールおよび類縁体および蛋白キナーゼ阻害剤としてのその使用 |
FR2854159B1 (fr) | 2003-04-25 | 2008-01-11 | Aventis Pharma Sa | Nouveaux derives de l'indole, leur preparation a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de kdr |
PT2298743E (pt) | 2003-06-26 | 2012-12-04 | Novartis Ag | Inibidores de p38 quinase a base de heterociclo de 5 elementos |
WO2006134318A1 (en) | 2005-06-11 | 2006-12-21 | Vernalis R & D Limited | Pyrazole-substituted benzimidazole derivatives for use in the treatment of cancer and autoimmune disorders |
US8399442B2 (en) | 2005-12-30 | 2013-03-19 | Astex Therapeutics Limited | Pharmaceutical compounds |
FR2903406B1 (fr) | 2006-07-04 | 2012-08-10 | Aventis Pharma Sa | Derives de pyrazolylbenzimidazole,compositions les contenant et utilisation |
RU2011106357A (ru) * | 2008-07-23 | 2012-08-27 | Ф.Хоффманн-Ля Рош Аг (Ch) | Гетероциклические антивирусные соединения |
AU2009273327A1 (en) * | 2008-07-23 | 2010-01-28 | F. Hoffmann-La Roche Ag | Heterocyclic antiviral compounds |
DK2471786T3 (en) | 2009-08-07 | 2016-01-25 | Chugai Pharmaceutical Co Ltd | aminopyrazole derivative |
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