UA80820C2 - N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors - Google Patents
N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors Download PDFInfo
- Publication number
- UA80820C2 UA80820C2 UA20041109391A UA20041109391A UA80820C2 UA 80820 C2 UA80820 C2 UA 80820C2 UA 20041109391 A UA20041109391 A UA 20041109391A UA 20041109391 A UA20041109391 A UA 20041109391A UA 80820 C2 UA80820 C2 UA 80820C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- group
- oalkyl
- mnalkyl
- halogenated
- Prior art date
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- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 title abstract description 5
- 108091006082 receptor inhibitors Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 586
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 1855
- -1 -OH Chemical group 0.000 claims description 358
- 125000003545 alkoxy group Chemical group 0.000 claims description 294
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 260
- 125000003118 aryl group Chemical group 0.000 claims description 249
- 150000002367 halogens Chemical class 0.000 claims description 220
- 229910052736 halogen Inorganic materials 0.000 claims description 218
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 186
- 125000001072 heteroaryl group Chemical group 0.000 claims description 184
- 125000004001 thioalkyl group Chemical group 0.000 claims description 169
- 125000003342 alkenyl group Chemical group 0.000 claims description 136
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 128
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 110
- 125000003282 alkyl amino group Chemical group 0.000 claims description 106
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 104
- 150000002825 nitriles Chemical class 0.000 claims description 97
- 125000001424 substituent group Chemical group 0.000 claims description 93
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 91
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 91
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 83
- 125000004149 thio group Chemical group *S* 0.000 claims description 75
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 52
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 41
- 230000027455 binding Effects 0.000 claims description 33
- 230000003287 optical effect Effects 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- 125000001153 fluoro group Chemical group F* 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 26
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 23
- 125000004414 alkyl thio group Chemical group 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 20
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- 229910052796 boron Inorganic materials 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000005647 linker group Chemical group 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 14
- 125000002757 morpholinyl group Chemical group 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004743 1-methylethoxycarbonyl group Chemical group CC(C)OC(=O)* 0.000 claims description 2
- 125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims description 2
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims description 2
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims 8
- 229910052801 chlorine Inorganic materials 0.000 claims 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 3
- RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical compound C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 claims 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 1
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 241001516584 Andrya Species 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 203
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 27
- 206010028980 Neoplasm Diseases 0.000 abstract description 16
- 230000002062 proliferating effect Effects 0.000 abstract description 14
- 239000003112 inhibitor Substances 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 7
- 108091008606 PDGF receptors Proteins 0.000 abstract description 3
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 abstract description 3
- 102000001253 Protein Kinase Human genes 0.000 abstract description 3
- 108060006633 protein kinase Proteins 0.000 abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 76
- 239000000543 intermediate Substances 0.000 description 64
- 239000000203 mixture Substances 0.000 description 62
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 43
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- 230000015572 biosynthetic process Effects 0.000 description 37
- 125000004432 carbon atom Chemical group C* 0.000 description 37
- 239000002904 solvent Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- 241000282414 Homo sapiens Species 0.000 description 29
- 229910052799 carbon Inorganic materials 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 229960000583 acetic acid Drugs 0.000 description 25
- 229910052740 iodine Inorganic materials 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 230000008569 process Effects 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 150000001721 carbon Chemical group 0.000 description 22
- 239000012267 brine Substances 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- 208000035475 disorder Diseases 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 18
- 239000000010 aprotic solvent Substances 0.000 description 16
- 238000004821 distillation Methods 0.000 description 16
- 230000007958 sleep Effects 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000003960 organic solvent Substances 0.000 description 15
- 239000013058 crude material Substances 0.000 description 14
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
- 239000012071 phase Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
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- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 108091000080 Phosphotransferase Proteins 0.000 description 11
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- 102000020233 phosphotransferase Human genes 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 125000004076 pyridyl group Chemical group 0.000 description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- IHMQOBPGHZFGLC-UHFFFAOYSA-N 5,6-dimethoxy-2,3-dihydroinden-1-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)CC2 IHMQOBPGHZFGLC-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 125000002883 imidazolyl group Chemical group 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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- 150000001412 amines Chemical class 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
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- 238000003786 synthesis reaction Methods 0.000 description 8
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 7
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
- C07F9/65038—Five-membered rings having the nitrogen atoms in the positions 1 and 2 condensed with carbocyclic rings or carbocyclic ring systems
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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PCT/US2003/015193 WO2003097609A1 (fr) | 2002-05-15 | 2003-05-13 | 3-aminopyrazoles tricycliques n-substitues comme inhibiteurs des recepteurs du pdfg |
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EP (1) | EP1506175B1 (fr) |
JP (1) | JP2006502097A (fr) |
KR (1) | KR20040106554A (fr) |
CN (1) | CN100396670C (fr) |
AR (1) | AR040079A1 (fr) |
AT (1) | ATE427301T1 (fr) |
AU (1) | AU2003234567A1 (fr) |
BR (1) | BRPI0311179A2 (fr) |
CA (1) | CA2486097A1 (fr) |
CR (1) | CR7574A (fr) |
DE (1) | DE60326950D1 (fr) |
EA (1) | EA008770B1 (fr) |
ES (1) | ES2323952T3 (fr) |
HR (1) | HRP20041188A2 (fr) |
IL (1) | IL165197A0 (fr) |
MX (1) | MXPA04011320A (fr) |
MY (1) | MY138268A (fr) |
NO (1) | NO20045451L (fr) |
NZ (1) | NZ548796A (fr) |
PE (1) | PE20040758A1 (fr) |
PL (1) | PL374062A1 (fr) |
RS (1) | RS98804A (fr) |
SA (1) | SA03240431A (fr) |
TW (1) | TW200407311A (fr) |
UA (1) | UA80820C2 (fr) |
UY (1) | UY27811A1 (fr) |
WO (1) | WO2003097609A1 (fr) |
ZA (1) | ZA200410108B (fr) |
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PL374062A1 (en) * | 2002-05-15 | 2005-09-19 | Janssen Pharmaceutica N.V. | N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors |
CN1914179A (zh) * | 2003-11-13 | 2007-02-14 | 詹森药业有限公司 | 用于生物分子靶标识别的固定的n-取代的三环3-氨基吡唑类 |
CA2551495A1 (fr) * | 2004-01-07 | 2005-07-28 | Ambit Biosciences Corporation | Petites molecules conjuguees |
WO2005123048A2 (fr) * | 2004-06-21 | 2005-12-29 | Proteome Sciences Plc | Methodes de criblage |
US7652029B2 (en) * | 2004-07-09 | 2010-01-26 | Medisyn Technologies, Inc. | Therapeutic compound and treatments |
WO2006044682A1 (fr) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Composés permettant de supprimer les effets des mutations non-sens, et méthodes d’emploi desdits composés |
JP2006321724A (ja) * | 2005-05-17 | 2006-11-30 | Tokyo Univ Of Science | 抗腫瘍剤 |
US20080031866A1 (en) * | 2006-06-20 | 2008-02-07 | Eichenbaum Gary M | Method for modulating the pharmacokinetics and metabolism of a therapeutic agent |
EP2037954A4 (fr) * | 2006-06-20 | 2011-09-14 | Janssen Pharmaceutica Nv | Méthode pour moduler les propriétés pharmacocinétiques et le métabolisme d'un agent thérapeutique |
JPWO2008093639A1 (ja) | 2007-01-29 | 2010-05-20 | 武田薬品工業株式会社 | ピラゾール化合物 |
WO2008094896A1 (fr) * | 2007-01-31 | 2008-08-07 | Janssen Pharmaceutica, N.V. | 3-aminopyrazoles tricycliques n-substitués comme inhibiteurs de polymérisation de la tubuline à effet anti-mitotique |
AU2008227875B2 (en) | 2007-03-19 | 2014-06-12 | Insuline Medical Ltd. | Drug delivery device |
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US8622991B2 (en) | 2007-03-19 | 2014-01-07 | Insuline Medical Ltd. | Method and device for drug delivery |
EP2231229A1 (fr) | 2007-12-18 | 2010-09-29 | Insuline Medical Ltd. | Dispositif d'administration de médicament doté d'un capteur pour un fonctionnement en boucle fermée |
RU2532893C2 (ru) | 2008-11-07 | 2014-11-10 | Инсьюлин Медикал Лтд. | Устройство и способ доставки лекарственных средств |
WO2011059784A1 (fr) * | 2009-10-29 | 2011-05-19 | Bristol-Myers Squibb Company | Composés hétérocycliques tricycliques |
WO2012088266A2 (fr) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Imidazopyridazines et benzimidazoles substitués en tant qu'inhibiteurs de fgfr3 |
WO2012121168A1 (fr) * | 2011-03-04 | 2012-09-13 | 国立大学法人京都大学 | Inhibiteur de kinase |
TWI553010B (zh) * | 2012-04-12 | 2016-10-11 | 財團法人生物技術開發中心 | 雜環吡唑化合物,其製備方法及用途 |
AR091424A1 (es) | 2012-06-13 | 2015-02-04 | Incyte Corp | Compuestos triciclicos sustituidos como inhibidores de receptores del factor de crecimiento del fibroplasto (fgfr) |
WO2014026125A1 (fr) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Dérivés de pyrazine en tant qu'inhibiteurs de fgfr |
WO2014039831A1 (fr) | 2012-09-07 | 2014-03-13 | Takeda Pharmaceutical Company Limited | Dihydropyrazolo[4,3-b]indoles substituées dans les positions 1 et 4 |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
PE20151593A1 (es) | 2013-03-14 | 2015-11-05 | Newlink Genetics Corp | Compuestos triciclicos como inhibidores de la inmunosupresion mediada por el metabolismo del triptofano |
TWI649318B (zh) | 2013-04-19 | 2019-02-01 | 英塞特控股公司 | 作為fgfr抑制劑之雙環雜環 |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
CN105884828A (zh) * | 2015-02-16 | 2016-08-24 | 上海迪诺医药科技有限公司 | 多环化合物、其药物组合物及应用 |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
MX2017010673A (es) | 2015-02-20 | 2018-03-21 | Incyte Corp | Heterociclos biciclicos como inhibidores de receptores del factor de crecimiento fibroblastico (fgfr). |
WO2016134294A1 (fr) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
EP3507278B1 (fr) | 2016-09-02 | 2021-01-27 | Bristol-Myers Squibb Company | Composés hétérocycliques tricycliques substitués |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
US11059784B2 (en) | 2017-08-09 | 2021-07-13 | Bristol-Myers Squibb Company | Oxime ether compounds |
WO2019032632A1 (fr) | 2017-08-09 | 2019-02-14 | Bristol-Myers Squibb Company | Composés d'alkylphényle |
MA52494A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Formes solides d'un inhibiteur de fgfr et leurs procédés de préparation |
CA3099116A1 (fr) | 2018-05-04 | 2019-11-07 | Incyte Corporation | Sels d'un inhibiteur de fgfr |
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 |
PE20221085A1 (es) | 2019-10-14 | 2022-07-05 | Incyte Corp | Heterociclos biciclicos como inhibidores de fgfr |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
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 |
US11407750B2 (en) | 2019-12-04 | 2022-08-09 | Incyte Corporation | Derivatives of an FGFR inhibitor |
AR126102A1 (es) | 2021-06-09 | 2023-09-13 | Incyte Corp | Heterociclos tricíclicos como inhibidores de fgfr |
WO2023081923A1 (fr) | 2021-11-08 | 2023-05-11 | Frequency Therapeutics, Inc. | Inhibiteurs du récepteur du facteur de croissance dérivé des plaquettes (pdgfr) alpha et leurs utilisations |
CN114890987B (zh) * | 2022-04-13 | 2023-12-19 | 万华化学集团股份有限公司 | 一种硫酚-噻吩配体及其制备方法、烯烃聚合催化剂及其制备方法、应用 |
CN114686427B (zh) * | 2022-05-23 | 2022-07-29 | 中国人民解放军总医院第一医学中心 | 一种脾脏调节型b淋巴细胞及其制备方法与应用 |
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PL374062A1 (en) * | 2002-05-15 | 2005-09-19 | Janssen Pharmaceutica N.V. | N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors |
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- 2003-05-13 JP JP2004505342A patent/JP2006502097A/ja not_active Withdrawn
- 2003-05-13 MX MXPA04011320A patent/MXPA04011320A/es active IP Right Grant
- 2003-05-13 RS YU98804A patent/RS98804A/sr unknown
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- 2003-05-13 DE DE60326950T patent/DE60326950D1/de not_active Expired - Fee Related
- 2003-05-13 AT AT03728909T patent/ATE427301T1/de not_active IP Right Cessation
- 2003-05-13 AU AU2003234567A patent/AU2003234567A1/en not_active Abandoned
- 2003-05-13 CN CNB038164884A patent/CN100396670C/zh not_active Expired - Fee Related
- 2003-05-13 BR BRPI0311179A patent/BRPI0311179A2/pt not_active IP Right Cessation
- 2003-05-13 NZ NZ548796A patent/NZ548796A/en unknown
- 2003-05-13 ES ES03728909T patent/ES2323952T3/es not_active Expired - Lifetime
- 2003-05-13 EP EP03728909A patent/EP1506175B1/fr not_active Expired - Lifetime
- 2003-05-13 UA UA20041109391A patent/UA80820C2/uk unknown
- 2003-05-13 CA CA002486097A patent/CA2486097A1/fr not_active Abandoned
- 2003-05-13 WO PCT/US2003/015193 patent/WO2003097609A1/fr active Application Filing
- 2003-05-13 EA EA200401378A patent/EA008770B1/ru not_active IP Right Cessation
- 2003-05-14 US US10/438,152 patent/US7196110B2/en not_active Expired - Lifetime
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- 2003-05-15 AR ARP030101696A patent/AR040079A1/es not_active Application Discontinuation
- 2003-05-15 UY UY27811A patent/UY27811A1/es not_active Application Discontinuation
- 2003-05-15 PE PE2003000466A patent/PE20040758A1/es not_active Application Discontinuation
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2004
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- 2004-12-14 NO NO20045451A patent/NO20045451L/no unknown
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2007
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