ES2580781T3 - Derivados heterociclilos bicíclicos como inhibidores de FGFR quinasa para uso terapéutico - Google Patents
Derivados heterociclilos bicíclicos como inhibidores de FGFR quinasa para uso terapéutico Download PDFInfo
- Publication number
- ES2580781T3 ES2580781T3 ES10718659.5T ES10718659T ES2580781T3 ES 2580781 T3 ES2580781 T3 ES 2580781T3 ES 10718659 T ES10718659 T ES 10718659T ES 2580781 T3 ES2580781 T3 ES 2580781T3
- Authority
- ES
- Spain
- Prior art keywords
- composite
- alkyl
- groups
- crxry
- heterocyclyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 108091008794 FGF receptors Proteins 0.000 title description 2
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 title description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title 1
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 3
- RAVIQFQJZMTUBX-AWEZNQCLSA-N 1-[(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-2-(3,4-dichlorophenyl)ethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(CC1=CC(=C(C=C1)Cl)Cl)=O RAVIQFQJZMTUBX-AWEZNQCLSA-N 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims 60
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 35
- 150000001875 compounds Chemical class 0.000 abstract description 29
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 29
- 239000001257 hydrogen Substances 0.000 abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 19
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 17
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract description 13
- 125000003118 aryl group Chemical group 0.000 abstract description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract description 10
- -1 C1-6 alkanol Chemical group 0.000 abstract description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 9
- 125000004452 carbocyclyl group Chemical group 0.000 abstract description 7
- 125000004122 cyclic group Chemical group 0.000 abstract description 7
- 150000002431 hydrogen Chemical group 0.000 abstract description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 6
- 229910052736 halogen Inorganic materials 0.000 abstract description 6
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 abstract description 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract description 4
- 150000002367 halogens Chemical group 0.000 abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 abstract description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 150000001204 N-oxides Chemical class 0.000 abstract 1
- 125000003282 alkyl amino group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 1
- 150000001721 carbon Chemical group 0.000 abstract 1
- 125000002950 monocyclic group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 3
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 2
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 2
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 2
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 239000012979 RPMI medium Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 102000058223 human VEGFA Human genes 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000011565 manganese chloride Substances 0.000 description 2
- 235000002867 manganese chloride Nutrition 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- VJLYHTOSFSGXGH-CQSZACIVSA-N (2R)-1-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2[C@H](CCC2)C(=O)O)C=CC=1 VJLYHTOSFSGXGH-CQSZACIVSA-N 0.000 description 1
- ZXAQFYZQHPGMMN-BZSJEYESSA-N (3R)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylcyclohexane-1-carboxamide Chemical compound C1C[C@H](CC(C1)C(=O)NC2=CC=CC=C2)OC3=CC(=CC(=N3)C(F)(F)F)CN ZXAQFYZQHPGMMN-BZSJEYESSA-N 0.000 description 1
- ZWHOTPNCEFWATE-CQSZACIVSA-N (3R)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpyrrolidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@H]1CN(CC1)C(=O)NC1=CC=CC=C1 ZWHOTPNCEFWATE-CQSZACIVSA-N 0.000 description 1
- ZWHOTPNCEFWATE-AWEZNQCLSA-N (3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpyrrolidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CC1)C(=O)NC1=CC=CC=C1 ZWHOTPNCEFWATE-AWEZNQCLSA-N 0.000 description 1
- SNAKUPLQASYKTC-AWEZNQCLSA-N (3S)-3-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC[C@@H]1CN(CCC1)C(=O)NC1=CC=CC=C1 SNAKUPLQASYKTC-AWEZNQCLSA-N 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- XAOMFUPJQYNDEG-LBPRGKRZSA-N 1-[(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-2-methylpropan-1-one Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(C(C)C)=O XAOMFUPJQYNDEG-LBPRGKRZSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
- MXILHVKNAYIRPJ-UHFFFAOYSA-N 2,3,7,7a-tetrahydro-1h-triazolo[4,5-b]pyrazine Chemical compound N1C=CN=C2NNNC21 MXILHVKNAYIRPJ-UHFFFAOYSA-N 0.000 description 1
- RNIUHIHTGPHJEN-AWEZNQCLSA-N 2-[(3S)-1-[2-(3,4-dichlorophenyl)acetyl]piperidin-3-yl]oxy-6-(trifluoromethyl)pyridine-4-carbonitrile Chemical compound ClC=1C=C(C=CC=1Cl)CC(=O)N1C[C@H](CCC1)OC=1C=C(C#N)C=C(N=1)C(F)(F)F RNIUHIHTGPHJEN-AWEZNQCLSA-N 0.000 description 1
- DCGQVDFBDSTUML-AWEZNQCLSA-N 2-[(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidine-1-carbonyl]chromen-4-one Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1OC2=CC=CC=C2C(C=1)=O DCGQVDFBDSTUML-AWEZNQCLSA-N 0.000 description 1
- APDYPEOKIUKUQV-UHFFFAOYSA-N 2-[1-(2-oxo-2-piperidin-1-ylethyl)indol-4-yl]oxy-6-(trifluoromethyl)pyridine-4-carbonitrile Chemical compound O=C(CN1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=C(N=1)C(F)(F)F)N1CCCCC1 APDYPEOKIUKUQV-UHFFFAOYSA-N 0.000 description 1
- BVKRPQCDGACLPX-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyindol-1-yl]-N-methyl-N-phenylacetamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1=C2C=CN(C2=CC=C1)CC(=O)N(C1=CC=CC=C1)C BVKRPQCDGACLPX-UHFFFAOYSA-N 0.000 description 1
- NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 1
- LDHYTBAFXANWKM-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one Chemical compound O=C1NC(N)=NC2=C1NC=N2.O=C1NC(N)=NC2=C1N=CN2 LDHYTBAFXANWKM-UHFFFAOYSA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
- UMZCLZPXPCNKML-UHFFFAOYSA-N 2h-imidazo[4,5-d][1,3]thiazole Chemical class C1=NC2=NCSC2=N1 UMZCLZPXPCNKML-UHFFFAOYSA-N 0.000 description 1
- WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 1
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 1
- CJYDQTAWSHWBIT-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxy-2-methylpropyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC(C)(C)O)C=CC=1 CJYDQTAWSHWBIT-UHFFFAOYSA-N 0.000 description 1
- MROVZCRMXJZHCN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxyethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCO)C=CC=1 MROVZCRMXJZHCN-UHFFFAOYSA-N 0.000 description 1
- SHBHYINHXNTBRP-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-methylsulfonylethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCS(=O)(=O)C)C=CC=1 SHBHYINHXNTBRP-UHFFFAOYSA-N 0.000 description 1
- LIDBMZYKSAXTQG-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-sulfamoylethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCS(N)(=O)=O)C=CC=1 LIDBMZYKSAXTQG-UHFFFAOYSA-N 0.000 description 1
- VTNULXUEOJMRKZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2H-tetrazol-5-ylmethyl)benzamide Chemical compound N=1NN=NC=1CNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O VTNULXUEOJMRKZ-UHFFFAOYSA-N 0.000 description 1
- SONNQRNOTIAJDS-GFCCVEGCSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(2R)-2,3-dihydroxypropyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC[C@H](CO)O)C=CC=1 SONNQRNOTIAJDS-GFCCVEGCSA-N 0.000 description 1
- GDSLUYKCPYECNN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(4-fluorophenyl)methyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC=C(C=C2)F)C=CC=1 GDSLUYKCPYECNN-UHFFFAOYSA-N 0.000 description 1
- ISXSUKUXUPLGTD-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(5-oxopyrrolidin-2-yl)methyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2NC(CC2)=O)C=CC=1 ISXSUKUXUPLGTD-UHFFFAOYSA-N 0.000 description 1
- FJPUKTJEFOXMJX-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[1-(hydroxymethyl)cyclopropyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2(CC2)CO)C=CC=1 FJPUKTJEFOXMJX-UHFFFAOYSA-N 0.000 description 1
- ZMCQQCBOZIGNRV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(1,2,4-triazol-1-yl)ethyl]benzamide Chemical compound NCC1=CC(OC2=CC=CC(=C2)C(=O)NCCN2C=NC=N2)=NC(=C1)C(F)(F)F ZMCQQCBOZIGNRV-UHFFFAOYSA-N 0.000 description 1
- FVQKGQNSCKJPIJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCN2C(OCC2)=O)C=CC=1 FVQKGQNSCKJPIJ-UHFFFAOYSA-N 0.000 description 1
- ZUNFPBNHELLPPP-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(dimethylamino)ethyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCN(C)C)C=CC=1 ZUNFPBNHELLPPP-UHFFFAOYSA-N 0.000 description 1
- AJZDHLHTTJRNQJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(tetrazol-1-yl)ethyl]benzamide Chemical compound N1(N=NN=C1)CCNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O AJZDHLHTTJRNQJ-UHFFFAOYSA-N 0.000 description 1
- MZSAMHOCTRNOIZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylaniline Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(NC2=CC=CC=C2)C=CC=1 MZSAMHOCTRNOIZ-UHFFFAOYSA-N 0.000 description 1
- HAEQAUJYNHQVHV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylbenzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 HAEQAUJYNHQVHV-UHFFFAOYSA-N 0.000 description 1
- XDADYJOYIMVXTH-UHFFFAOYSA-N 3h-imidazo[1,2-a]imidazole Chemical compound C1=CN2CC=NC2=N1 XDADYJOYIMVXTH-UHFFFAOYSA-N 0.000 description 1
- YCVAGNVTZICLNM-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzofuran Chemical compound C1CCCC2=C1C=CO2 YCVAGNVTZICLNM-UHFFFAOYSA-N 0.000 description 1
- QEIVWSRXBYOTAZ-UHFFFAOYSA-N 4-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1CCN(CC1)C(=O)NC1=CC=CC=C1 QEIVWSRXBYOTAZ-UHFFFAOYSA-N 0.000 description 1
- HOWFLZVASJDZRZ-UHFFFAOYSA-N 4-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OCC1CCN(CC1)C(=O)NC1=CC=CC=C1 HOWFLZVASJDZRZ-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- UMEIYBJBGZKZOS-UHFFFAOYSA-N 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1NCCN2C=NN=C21 UMEIYBJBGZKZOS-UHFFFAOYSA-N 0.000 description 1
- FOFSNCRMWLKAIM-UHFFFAOYSA-N 5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-3,4-dihydro-1H-quinolin-2-one Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1=C2CCC(NC2=CC=C1)=O FOFSNCRMWLKAIM-UHFFFAOYSA-N 0.000 description 1
- ZFYXJIYPIORSQE-UHFFFAOYSA-N 5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-methylsulfonylethyl)pyridine-3-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=NC=C(C(=O)NCCS(=O)(=O)C)C=1 ZFYXJIYPIORSQE-UHFFFAOYSA-N 0.000 description 1
- NRLQBVLOUUPAMI-UHFFFAOYSA-N 8-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2CCC3(CNC(O3)=O)CC2)C=CC=1 NRLQBVLOUUPAMI-UHFFFAOYSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 101001033276 Mus musculus Interleukin-3 Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- JDCLUYDBENDDSR-NSHDSACASA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-(5-methyl-1,3,4-oxadiazol-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1OC(=NN=1)C JDCLUYDBENDDSR-NSHDSACASA-N 0.000 description 1
- RWQJLIWMOBYOTI-AWEZNQCLSA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-pyridin-3-ylmethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1C=NC=CC=1 RWQJLIWMOBYOTI-AWEZNQCLSA-N 0.000 description 1
- WGCOQYDRMPFAMN-ZDUSSCGKSA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-pyrimidin-5-ylmethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1C=NC=NC=1 WGCOQYDRMPFAMN-ZDUSSCGKSA-N 0.000 description 1
- SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 description 1
- PKZVFOVXYKCBCJ-UHFFFAOYSA-N [2-(1H-indol-4-yloxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1C=CC2=C(C=CC=C12)OC1=NC(=CC(=C1)CN)C(F)(F)F PKZVFOVXYKCBCJ-UHFFFAOYSA-N 0.000 description 1
- ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
- GXFIJNNOECYQOJ-UHFFFAOYSA-N [2-[1-(1-methylpyrazol-4-yl)indol-4-yl]oxy-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound CN1N=CC(=C1)N1C=CC2=C(C=CC=C12)OC1=NC(=CC(=C1)CN)C(F)(F)F GXFIJNNOECYQOJ-UHFFFAOYSA-N 0.000 description 1
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 1
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- YQYBUJYBXOVWQW-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 YQYBUJYBXOVWQW-UHFFFAOYSA-N 0.000 description 1
- YKKPYMXANSSQCA-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3-pyrazol-1-ylazetidin-1-yl)methanone Chemical compound N1(N=CC=C1)C1CN(C1)C(=O)C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F YKKPYMXANSSQCA-UHFFFAOYSA-N 0.000 description 1
- JOSCNYCOYXTLTN-GFCCVEGCSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)CO JOSCNYCOYXTLTN-GFCCVEGCSA-N 0.000 description 1
- BYWBCSRCPLBDFU-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-aminopyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)N BYWBCSRCPLBDFU-CYBMUJFWSA-N 0.000 description 1
- LJHFUFVRZNYVMK-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)O LJHFUFVRZNYVMK-CYBMUJFWSA-N 0.000 description 1
- LJHFUFVRZNYVMK-ZDUSSCGKSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@H](CC1)O LJHFUFVRZNYVMK-ZDUSSCGKSA-N 0.000 description 1
- KDSYNTPPPISIJB-UHFFFAOYSA-N [3-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]phenyl]-(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone Chemical compound NCc1cc(OCc2cccc(c2)C(=O)N2CC(O)C(F)C2)nc(c1)C(F)(F)F KDSYNTPPPISIJB-UHFFFAOYSA-N 0.000 description 1
- UGKIKJFPXNOHHA-UHFFFAOYSA-N [5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypyridin-3-yl]-(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=NC=1)C(=O)N1CC(C(C1)O)F UGKIKJFPXNOHHA-UHFFFAOYSA-N 0.000 description 1
- IQUWAPNUQVLWGG-GFCCVEGCSA-N [5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypyridin-3-yl]-[(3R)-3-aminopyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=NC=1)C(=O)N1C[C@@H](CC1)N IQUWAPNUQVLWGG-GFCCVEGCSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ZVHRTJHLSYKEAK-UHFFFAOYSA-N ethyl 2-[5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-2-oxo-3,4-dihydroquinolin-1-yl]acetate Chemical compound CCOC(=O)CN1C(=O)CCC2=C1C=CC=C2OC1=NC(=CC(CN)=C1)C(F)(F)F ZVHRTJHLSYKEAK-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 1
- CQQJSOXDEFZGFG-UHFFFAOYSA-N imidazo[4,5-d]imidazole Chemical class C1=NC2=NC=NC2=N1 CQQJSOXDEFZGFG-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 1
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000003375 selectivity assay Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- HONNWTDYWUAZJF-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyindol-1-yl]acetyl]piperazine-1-carboxylate Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1=C2C=CN(C2=CC=C1)CC(=O)N1CCN(CC1)C(=O)OC(C)(C)C HONNWTDYWUAZJF-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Classifications
-
- 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
- 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
- C07D471/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16948709P | 2009-04-15 | 2009-04-15 | |
| GB0906472 | 2009-04-15 | ||
| GBGB0906472.6A GB0906472D0 (en) | 2009-04-15 | 2009-04-15 | New compounds |
| US169487P | 2009-04-15 | ||
| PCT/GB2010/050617 WO2010119284A1 (en) | 2009-04-15 | 2010-04-15 | Bicyclic heterocyclyl derivatives as fgfr kinase inhibitors for therapeutic use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2580781T3 true ES2580781T3 (es) | 2016-08-26 |
Family
ID=40750627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10718659.5T Active ES2580781T3 (es) | 2009-04-15 | 2010-04-15 | Derivados heterociclilos bicíclicos como inhibidores de FGFR quinasa para uso terapéutico |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8481531B2 (enExample) |
| EP (1) | EP2419427B1 (enExample) |
| JP (1) | JP5718897B2 (enExample) |
| AU (1) | AU2010238289B2 (enExample) |
| CA (1) | CA2757592C (enExample) |
| CY (1) | CY1118061T1 (enExample) |
| DK (1) | DK2419427T3 (enExample) |
| ES (1) | ES2580781T3 (enExample) |
| GB (1) | GB0906472D0 (enExample) |
| HR (1) | HRP20160725T1 (enExample) |
| HU (1) | HUE028138T2 (enExample) |
| ME (1) | ME02463B (enExample) |
| PL (1) | PL2419427T3 (enExample) |
| PT (1) | PT2419427T (enExample) |
| RS (1) | RS55038B1 (enExample) |
| SI (1) | SI2419427T1 (enExample) |
| SM (1) | SMT201600220B (enExample) |
| WO (1) | WO2010119284A1 (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2672213C (en) | 2006-12-22 | 2016-02-16 | Astex Therapeutics Limited | Bicyclic amine derivatives as protein tyrosine kinase inhibitors |
| US8895745B2 (en) | 2006-12-22 | 2014-11-25 | Astex Therapeutics Limited | Bicyclic heterocyclic compounds as FGFR inhibitors |
| GB0720041D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New Compounds |
| GB0720038D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New compounds |
| GB0810902D0 (en) | 2008-06-13 | 2008-07-23 | Astex Therapeutics Ltd | New compounds |
| GB0906472D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| GB0906470D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| KR20140078710A (ko) | 2011-09-30 | 2014-06-25 | 온코디자인 에스.에이. | 거대고리 flt3 키나제 억제제 |
| UA111382C2 (uk) | 2011-10-10 | 2016-04-25 | Оріон Корпорейшн | Інгібітори протеїнкінази |
| HUE042374T2 (hu) | 2012-06-13 | 2019-06-28 | Incyte Holdings Corp | Szubsztituált triciklusos vegyületek mint FGFR inhibitorok |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| 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 |
| US9834520B2 (en) | 2013-03-14 | 2017-12-05 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| TWI628176B (zh) * | 2013-04-04 | 2018-07-01 | 奧利安公司 | 蛋白質激酶抑制劑 |
| KR102469849B1 (ko) | 2013-04-19 | 2022-11-23 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| AU2014338549B2 (en) | 2013-10-25 | 2017-05-25 | Novartis Ag | Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors |
| AR098145A1 (es) * | 2013-10-25 | 2016-05-04 | Novartis Ag | Compuestos derivados de piridilo bicíclicos fusionados como inhibidores de fgfr4 |
| KR102344105B1 (ko) | 2014-08-18 | 2021-12-29 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 모노시클릭 피리딘 유도체의 염 및 이의 결정 |
| EP3200786B1 (en) * | 2014-10-03 | 2019-08-28 | Novartis AG | Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
| 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 |
| AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| CN114984013A (zh) | 2015-03-25 | 2022-09-02 | 国立癌症研究中心 | 胆管癌治疗剂 |
| US9802917B2 (en) | 2015-03-25 | 2017-10-31 | Novartis Ag | Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide |
| SG10201913989QA (en) | 2015-10-16 | 2020-03-30 | 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 |
| 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 |
| 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 |
| 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 |
| US12365689B2 (en) | 2015-10-16 | 2025-07-22 | 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 |
| WO2017104739A1 (ja) | 2015-12-17 | 2017-06-22 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 乳がん治療剤 |
| EP3498707A4 (en) * | 2016-08-12 | 2020-04-08 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | FGFR4 INHIBITOR, PREPARATION METHOD THEREOF AND USE THEREOF |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| SG11202007591RA (en) | 2018-03-28 | 2020-09-29 | Eisai R&D Man Co Ltd | Therapeutic agent for hepatocellular carcinoma |
| EP3788046B1 (en) | 2018-05-04 | 2025-12-10 | Incyte Corporation | Salts of an fgfr inhibitor |
| EP4309737A3 (en) | 2018-05-04 | 2024-03-27 | Incyte Corporation | Solid forms of an fgfr inhibitor and processes for preparing the same |
| KR102878873B1 (ko) | 2019-02-14 | 2025-10-31 | 브리진 바이오사이언시스, 인코포레이티드 | 암 치료를 위한 fgfr 억제제 |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021018047A1 (zh) | 2019-07-26 | 2021-02-04 | 南京明德新药研发有限公司 | 作为fgfr和vegfr双重抑制剂的吡啶衍生物 |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021076602A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | 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 |
| KR20220131900A (ko) | 2019-12-04 | 2022-09-29 | 인사이트 코포레이션 | Fgfr 억제제의 유도체 |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4286382A4 (en) * | 2021-01-26 | 2025-01-08 | CGeneTech (Suzhou, China) Co., Ltd. | CRYSTAL FORM OF A METHYLPYRAZOLE-SUBSTITUTED PYRIDOIMIDAZOLE COMPOUND AND METHOD FOR PREPARING THE SAME |
| CA3215903A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| KR20240170936A (ko) * | 2022-03-31 | 2024-12-05 | 에이스랜드 테라퓨틱스 (홍콩) 리미티드 | 스피로비시클릭 화합물 |
| WO2024091370A1 (en) * | 2022-10-26 | 2024-05-02 | Acerand Therapeutics (Usa) Limited | 5,6-fused bicyclic heteroaromatic compounds |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5554630A (en) | 1993-03-24 | 1996-09-10 | Neurosearch A/S | Benzimidazole compounds |
| ATE210663T1 (de) | 1994-06-20 | 2001-12-15 | Takeda Chemical Industries Ltd | Kondensierte imidazolderivate, ihre herstellung und verwendung |
| WO1996034866A1 (en) | 1995-05-01 | 1996-11-07 | Fujisawa Pharmaceutical Co., Ltd. | Imidazo 1,2-a pyridine and imidazo 1,2-a pyridezine derivatives and their use as bone resorption inhibitors |
| WO1997012613A1 (en) | 1995-10-05 | 1997-04-10 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
| EP0915880B1 (en) | 1996-07-24 | 2007-10-10 | Bristol-Myers Squibb Pharma Company | Azolo triazines and pyrimidines |
| EP0984692A4 (en) | 1997-05-30 | 2001-02-21 | Merck & Co Inc | ANGIOGENESIS INHIBITORS |
| US5990146A (en) | 1997-08-20 | 1999-11-23 | Warner-Lambert Company | Benzimidazoles for inhibiting protein tyrosine kinase mediated cellular proliferation |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| WO2000012089A1 (en) | 1998-08-31 | 2000-03-09 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| ATE301657T1 (de) | 1998-01-28 | 2005-08-15 | Bristol Myers Squibb Pharma Co | Azolo-pyrimidine |
| US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| JP2003503354A (ja) | 1999-06-30 | 2003-01-28 | メルク エンド カムパニー インコーポレーテッド | Ｓｒｃキナーゼ阻害剤化合物 |
| DE60006541D1 (de) | 1999-06-30 | 2003-12-18 | Merck & Co Inc | Src-kinase hemmende verbindungen |
| CA2376957A1 (en) | 1999-06-30 | 2001-01-04 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| JP2001057292A (ja) | 1999-08-20 | 2001-02-27 | Toray Ind Inc | 発光素子 |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| GB9921150D0 (en) | 1999-09-07 | 1999-11-10 | Merck Sharp & Dohme | Therapeutic agents |
| WO2001021634A1 (en) | 1999-09-21 | 2001-03-29 | Lion Bioscience Ag | Benzimidazole derivatives and combinatorial libraries thereof |
| GB9927687D0 (en) | 1999-11-23 | 2000-01-19 | Merck Sharp & Dohme | Therapeutic agents |
| ATE414079T1 (de) | 2000-03-01 | 2008-11-15 | Janssen Pharmaceutica Nv | 2,4-disubstituierte thiazolyl derivate |
| IL151517A0 (en) | 2000-03-09 | 2003-04-10 | Aventis Pharma Gmbh | Therapeutic uses of ppar mediators |
| US20020041880A1 (en) | 2000-07-05 | 2002-04-11 | Defeo-Jones Deborah | Method of treating cancer |
| MXPA02011263A (es) | 2000-08-04 | 2003-03-10 | Warner Lambert Co | 2-(4-piridil)amino-6-dialcoxifenil- pirido(2,3-d) pirimidin-7-onas. |
| WO2002034748A1 (fr) | 2000-10-24 | 2002-05-02 | Sankyo Company, Limited | Derives d'imidazopyridine |
| GB0027561D0 (en) | 2000-11-10 | 2000-12-27 | Merck Sharp & Dohme | Therapeutic agents |
| WO2002046168A1 (en) | 2000-12-07 | 2002-06-13 | Astrazeneca Ab | Therapeutic benzimidazole compounds |
| US20020107262A1 (en) | 2000-12-08 | 2002-08-08 | 3M Innovative Properties Company | Substituted imidazopyridines |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| SE0100568D0 (sv) | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | Compounds |
| SE0100567D0 (sv) | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | Compounds |
| DE60230160D1 (de) | 2001-02-20 | 2009-01-15 | Astrazeneca Ab | 2-arylaminopyrimidine zur behandlung von mit gsk3 in zusammenhang stehenden erkrankungen |
| TWI248936B (en) | 2001-03-21 | 2006-02-11 | Merck Sharp & Dohme | Imidazo-pyrimidine derivatives as ligands for GABA receptors |
| DE10117183A1 (de) | 2001-04-05 | 2002-10-10 | Gruenenthal Gmbh | Verwendung von substituierten Imidazo[1,2-a]-pyridinverbindungen als Arzneimittel |
| DE60227794D1 (de) | 2001-04-26 | 2008-09-04 | Eisai R&D Man Co Ltd | Stickstoffhaltige verbindung mit kondensiertem ring und pyrazolylgruppe als substituent und medizinische zusammensetzung davon |
| WO2003007955A2 (en) | 2001-07-20 | 2003-01-30 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| GB0128499D0 (en) | 2001-11-28 | 2002-01-23 | Merck Sharp & Dohme | Therapeutic agents |
| US6900208B2 (en) | 2002-03-28 | 2005-05-31 | Bristol Myers Squibb Company | Pyrrolopyridazine compounds and methods of use thereof for the treatment of proliferative disorders |
| CN100343255C (zh) | 2002-04-23 | 2007-10-17 | 盐野义制药株式会社 | 吡唑并[1,5－a]嘧啶衍生物和含有该衍生物的NAD(P)H氧化酶抑制剂 |
| JP2004002826A (ja) | 2002-04-24 | 2004-01-08 | Sankyo Co Ltd | 高分子イミダゾピリジン誘導体 |
| US7125888B2 (en) | 2002-05-02 | 2006-10-24 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| IL165262A0 (en) | 2002-05-23 | 2005-12-18 | Cytopia Pty Ltd | Kinase inhibitors |
| GB0212048D0 (en) | 2002-05-24 | 2002-07-03 | Merck Sharp & Dohme | Therapeutic agents |
| GB0212049D0 (en) | 2002-05-24 | 2002-07-03 | Merck Sharp & Dohme | Therapeutic agents |
| EP1511751B1 (en) | 2002-06-04 | 2008-03-19 | Neogenesis Pharmaceuticals, Inc. | Pyrazolo[1,5-a]pyrimidine compounds as antiviral agents |
| PA8577501A1 (es) | 2002-07-25 | 2004-02-07 | Warner Lambert Co | Inhibidores de quinasas |
| AR041291A1 (es) | 2002-09-19 | 2005-05-11 | Schering Corp | Imidazopiridinas como inhibidores de quinasa dependientes de ciclina |
| GB0223349D0 (en) | 2002-10-08 | 2002-11-13 | Merck Sharp & Dohme | Therapeutic agents |
| WO2004035579A1 (ja) | 2002-10-15 | 2004-04-29 | Takeda Pharmaceutical Company Limited | イミダゾピリジン誘導体、その製造法および用途 |
| US7550470B2 (en) | 2002-12-11 | 2009-06-23 | Merck & Co. Inc. | Substituted pyrazolo[1,5-A]pyrimidines as tyrosine kinase inhibitors |
| AU2003298942A1 (en) | 2002-12-11 | 2004-06-30 | Merck And Co., Inc. | Tyrosine kinase inhibitors |
| WO2004075021A2 (en) | 2003-02-14 | 2004-09-02 | Vertex Pharmaceuticals, Inc. | Molecular modeling methods |
| US7476670B2 (en) | 2003-02-18 | 2009-01-13 | Aventis Pharma S.A. | Purine derivatives, method for preparing, pharmaceutical compositions and novel use |
| US7157460B2 (en) | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7893096B2 (en) | 2003-03-28 | 2011-02-22 | Novartis Vaccines And Diagnostics, Inc. | Use of small molecule compounds for immunopotentiation |
| US7521448B2 (en) | 2003-08-21 | 2009-04-21 | Osi Pharmaceuticals, Inc. | N-substituted benzimidazolyl c-Kit inhibitors |
| US7442709B2 (en) | 2003-08-21 | 2008-10-28 | Osi Pharmaceuticals, Inc. | N3-substituted imidazopyridine c-Kit inhibitors |
| EP1658289B1 (en) | 2003-08-21 | 2009-03-18 | OSI Pharmaceuticals, Inc. | 3-substituted imidazopyridine-derivatives as c-kit inhibitors |
| US7737143B2 (en) | 2003-12-03 | 2010-06-15 | Ym Biosciences Australia Pty Ltd | Substituted pyrazines as kinase inhibitors |
| WO2005075470A1 (en) | 2004-01-28 | 2005-08-18 | Smithkline Beecham Corporation | Thiazole compounds |
| TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| AU2005240942B2 (en) | 2004-05-10 | 2010-08-05 | Banyu Pharmaceutical Co., Ltd. | Imidazopyridine compound |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| CN101048406B (zh) | 2004-08-31 | 2010-12-22 | 万有制药株式会社 | 新型取代的咪唑衍生物 |
| KR20070057965A (ko) | 2004-09-21 | 2007-06-07 | 신타 파마슈티칼스 코프. | 염증 및 면역 관련 용도를 위한 화합물 |
| WO2006038001A1 (en) | 2004-10-06 | 2006-04-13 | Celltech R & D Limited | Aminopyrimidine derivatives as jnk inhibitors |
| ATE521604T1 (de) | 2004-12-01 | 2011-09-15 | Osi Pharm Inc | N-substituierte benzimidazolyl-c-kit-inhibitoren und kombinatorische benzimidazolbibliothek |
| CA2594325A1 (en) | 2004-12-28 | 2006-07-06 | Takeda Pharmaceutical Company Limited | Condensed imidazole compound and use thereof |
| JP2008526723A (ja) | 2004-12-30 | 2008-07-24 | アステックス、セラピューティックス、リミテッド | Ｃｄｋ、ｇｓｋ及びオーロラキナーゼの活性を調節するピラゾール誘導体 |
| DOP2006000051A (es) | 2005-02-24 | 2006-08-31 | Lilly Co Eli | Inhibidores de vegf-r2 y métodos |
| CA2599987A1 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | Fused heterocyclic compounds and their use as sirtuin modulators |
| AU2006232105A1 (en) | 2005-04-05 | 2006-10-12 | Pharmacopeia, Inc. | Purine and imidazopyridine derivatives for immunosuppression |
| FR2884821B1 (fr) | 2005-04-26 | 2007-07-06 | Aventis Pharma Sa | Pyrrolopyridines substitues, compositions les contenant, procede de fabrication et utilisation |
| US7572807B2 (en) | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| CA2623374A1 (en) | 2005-09-30 | 2007-04-05 | Astrazeneca Ab | Imidazo [1,2-a] pyridine having anti-cell-proliferation activity |
| CA2645434A1 (en) | 2006-03-20 | 2007-09-27 | Synta Pharmaceutical Corp. | Benzoimidazolyl-parazine compounds for inflammation and immune-related uses |
| WO2007112093A2 (en) | 2006-03-23 | 2007-10-04 | Synta Pharmaceuticals Corp. | Benzimidazolyl-pyridine compounds for inflammation and immune-related uses |
| ITVA20060041A1 (it) | 2006-07-05 | 2008-01-06 | Dialectica Srl | Uso di composti derivati amminotiazolici, di loro composizioni farmaceutiche, nel trattamento di malattie caratterizzate dalla anormale repressione della trascrizione genica, particolarmente il morbo di huntington |
| TW200811134A (en) | 2006-07-12 | 2008-03-01 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| EP1882475A1 (en) | 2006-07-26 | 2008-01-30 | Novartis AG | Method of treating disorders mediated by the fibroblast growth factor receptor |
| US7737149B2 (en) | 2006-12-21 | 2010-06-15 | Astrazeneca Ab | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide and salts thereof |
| US8895745B2 (en) * | 2006-12-22 | 2014-11-25 | Astex Therapeutics Limited | Bicyclic heterocyclic compounds as FGFR inhibitors |
| US8131527B1 (en) | 2006-12-22 | 2012-03-06 | Astex Therapeutics Ltd. | FGFR pharmacophore compounds |
| CA2672213C (en) * | 2006-12-22 | 2016-02-16 | Astex Therapeutics Limited | Bicyclic amine derivatives as protein tyrosine kinase inhibitors |
| US7977336B2 (en) | 2006-12-28 | 2011-07-12 | Banyu Pharmaceutical Co. Ltd | Aminopyrimidine derivatives as PLK1 inhibitors |
| JP5374492B2 (ja) | 2007-04-03 | 2013-12-25 | アレイ バイオファーマ、インコーポレイテッド | 受容体チロシンキナーゼ阻害薬としてのイミダゾ［１，２−ａ］ピリジン化合物 |
| EP2170814B1 (en) | 2007-06-12 | 2016-08-17 | Achaogen, Inc. | Antibacterial agents |
| US20090005374A1 (en) | 2007-06-26 | 2009-01-01 | Melvin Jr Lawrence S | Imidazopyridinyl thiazolyl histone deacetylase inhibitors |
| GB0720038D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New compounds |
| GB0720041D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New Compounds |
| GB0810902D0 (en) | 2008-06-13 | 2008-07-23 | Astex Therapeutics Ltd | New compounds |
| GB0906470D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| GB0906472D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
-
2009
- 2009-04-15 GB GBGB0906472.6A patent/GB0906472D0/en not_active Ceased
-
2010
- 2010-04-15 PL PL10718659.5T patent/PL2419427T3/pl unknown
- 2010-04-15 SI SI201031219A patent/SI2419427T1/sl unknown
- 2010-04-15 CA CA2757592A patent/CA2757592C/en active Active
- 2010-04-15 EP EP10718659.5A patent/EP2419427B1/en active Active
- 2010-04-15 US US13/264,593 patent/US8481531B2/en not_active Expired - Fee Related
- 2010-04-15 HU HUE10718659A patent/HUE028138T2/en unknown
- 2010-04-15 JP JP2012505238A patent/JP5718897B2/ja not_active Expired - Fee Related
- 2010-04-15 DK DK10718659.5T patent/DK2419427T3/en active
- 2010-04-15 HR HRP20160725TT patent/HRP20160725T1/hr unknown
- 2010-04-15 WO PCT/GB2010/050617 patent/WO2010119284A1/en not_active Ceased
- 2010-04-15 PT PT107186595T patent/PT2419427T/pt unknown
- 2010-04-15 ES ES10718659.5T patent/ES2580781T3/es active Active
- 2010-04-15 RS RS20160503A patent/RS55038B1/sr unknown
- 2010-04-15 AU AU2010238289A patent/AU2010238289B2/en not_active Ceased
- 2010-04-15 ME MEP-2016-133A patent/ME02463B/me unknown
-
2016
- 2016-07-05 SM SM201600220T patent/SMT201600220B/it unknown
- 2016-07-05 CY CY20161100619T patent/CY1118061T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUE028138T2 (en) | 2016-12-28 |
| GB0906472D0 (en) | 2009-05-20 |
| JP5718897B2 (ja) | 2015-05-13 |
| EP2419427A1 (en) | 2012-02-22 |
| SMT201600220B (it) | 2016-08-31 |
| CA2757592A1 (en) | 2010-10-21 |
| PT2419427T (pt) | 2016-07-13 |
| ME02463B (me) | 2017-02-20 |
| CY1118061T1 (el) | 2017-06-28 |
| DK2419427T3 (en) | 2016-07-18 |
| US8481531B2 (en) | 2013-07-09 |
| JP2012524055A (ja) | 2012-10-11 |
| SI2419427T1 (sl) | 2016-08-31 |
| AU2010238289A1 (en) | 2011-12-08 |
| CA2757592C (en) | 2018-08-21 |
| AU2010238289B2 (en) | 2015-12-03 |
| WO2010119284A1 (en) | 2010-10-21 |
| US20120035171A1 (en) | 2012-02-09 |
| HRP20160725T1 (hr) | 2016-09-23 |
| EP2419427B1 (en) | 2016-04-06 |
| PL2419427T3 (pl) | 2016-12-30 |
| RS55038B1 (sr) | 2016-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2580781T3 (es) | Derivados heterociclilos bicíclicos como inhibidores de FGFR quinasa para uso terapéutico | |
| ES2544477T3 (es) | Imidazoquinolinas sustituidas con alcoxi | |
| CN114981268B (zh) | 嘧啶-4(3h)-酮类杂环化合物、其制备方法及其在医药学上的应用 | |
| CA2778680C (en) | N-containing heteroaryl derivatives as jak3 kinase inhibitors | |
| KR101862493B1 (ko) | Fgfr4 억제제로서의 고리-융합된 비시클릭 피리딜 유도체 | |
| ES2757948T3 (es) | Compuestos heterocíclicos como inhibidores LSD1 | |
| RU2028297C1 (ru) | Производные пиримидин-4-она или их фармацевтически приемлемые соли и серотонинантагонистическая, допаминантагонистическая и антигистаминная композиция на их основе | |
| KR101609412B1 (ko) | 아자 2 고리형 화합물 또는 그 염 | |
| ES2955132T3 (es) | Compuestos heterocíclicos sustituidos con amina como inhibidores de EHMT2 y métodos de uso de los mismos | |
| CA2897333C (en) | Thiazolecarboxamides and pyridinecarboxamide compounds useful as pim kinase inhibitors | |
| IL319814A (en) | A novel inhibitor of protein arginine methyltransferase 5 and its use | |
| ES2427999T3 (es) | Compuestos heterocíclicos 2-cianofenil-condensados y composiciones y usos de los mismos | |
| ES2899665T3 (es) | Derivados de 2-(3-(1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol y compuestos relacionados como inhibidores de PRS para el tratamiento, p. ej., del cáncer | |
| KR20060005333A (ko) | 특정의 신규한 이미다조피리딘 및 그의 용도 | |
| EP1244672A1 (en) | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors | |
| KR20100053626A (ko) | 5-ｈｔ6 수용체 친화성을 나타내는 3'-치환된 화합물 | |
| KR20080107466A (ko) | 대사 장애 치료용 8-헤테로아릴퓨린 ｍｎｋ2 억제제 | |
| CN107406442A (zh) | 作为egfr抑制剂的新的嘧啶和治疗病症的方法 | |
| AU2016208906A1 (en) | JAK inhibitor | |
| KR20150053894A (ko) | 증식성 질환의 치료를 위한 키나제 저해제로서 유용한 다이하이드로나프타이리딘 및 관련 화합물 | |
| ES2586527T9 (es) | Compuestos heterocíclicos y uso de los mismos como moduladores del receptor de tirosina quinasas de tipo III | |
| RU2037495C1 (ru) | 2,9-дизамещенные 4н-пиридо(1,2-а)-пиримидин-4-оны и противопсихотическая композиция | |
| CA2987466A1 (en) | Use of pteridinone derivative serving as egfr inhibitor | |
| EP3459952A1 (en) | Pyrimidine derivative, method for preparing same and use thereof in medicine | |
| RS54595B1 (sr) | Derivati 2-okso-1-pirolidinil imidazotiadiazola |