ES2289336T3 - Derivados heteroarilicos condensados para su uso como inhibidores de quinasa p38 en el tratamiento de, entre otras, artritis reumatoide. - Google Patents
Derivados heteroarilicos condensados para su uso como inhibidores de quinasa p38 en el tratamiento de, entre otras, artritis reumatoide. Download PDFInfo
- Publication number
- ES2289336T3 ES2289336T3 ES03771208T ES03771208T ES2289336T3 ES 2289336 T3 ES2289336 T3 ES 2289336T3 ES 03771208 T ES03771208 T ES 03771208T ES 03771208 T ES03771208 T ES 03771208T ES 2289336 T3 ES2289336 T3 ES 2289336T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- cyclopropyl
- indazol
- alkyl
- optionally substituted
- 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.)
- Expired - Lifetime
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- 238000011282 treatment Methods 0.000 title claims abstract description 14
- 239000012826 P38 inhibitor Substances 0.000 title description 3
- 206010003246 arthritis Diseases 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 271
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims abstract description 36
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract description 16
- 230000000694 effects Effects 0.000 claims abstract description 13
- 230000001404 mediated effect Effects 0.000 claims abstract description 12
- 102000004127 Cytokines Human genes 0.000 claims abstract description 9
- 108090000695 Cytokines Proteins 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 160
- 238000000034 method Methods 0.000 claims description 150
- 239000000203 mixture Substances 0.000 claims description 121
- 229910052757 nitrogen Inorganic materials 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- -1 -CONHR 13 Chemical group 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 35
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 34
- 239000001301 oxygen Substances 0.000 claims description 34
- 125000005842 heteroatom Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical group FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 239000011593 sulfur Substances 0.000 claims description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 239000003981 vehicle Substances 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 239000000460 chlorine Chemical group 0.000 claims description 9
- 229910052801 chlorine Chemical group 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 229910052731 fluorine Chemical group 0.000 claims description 8
- 239000011737 fluorine Chemical group 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- OZHIRVJSSIUZJL-UHFFFAOYSA-N 3-(1-butylsulfonylindazol-5-yl)-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound C=1C=C2N(S(=O)(=O)CCCC)N=CC2=CC=1C(C(=C(F)C=1)C)=CC=1C(=O)NC1CC1 OZHIRVJSSIUZJL-UHFFFAOYSA-N 0.000 claims description 3
- NCXDBVWGXNNHSL-UHFFFAOYSA-N 3-[1-(2-chlorophenyl)sulfonylindazol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1Cl NCXDBVWGXNNHSL-UHFFFAOYSA-N 0.000 claims description 3
- KQRGLFSUSWBGTL-UHFFFAOYSA-N 3-[1-(2-cyanophenyl)sulfonylindazol-5-yl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1C#N KQRGLFSUSWBGTL-UHFFFAOYSA-N 0.000 claims description 3
- FOMFZXYSLLFJRP-UHFFFAOYSA-N 3-[1-(5-chlorothiophen-2-yl)sulfonylindazol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=C(Cl)S1 FOMFZXYSLLFJRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 230000002969 morbid Effects 0.000 claims description 3
- DMTJDVSGJMJVRQ-UHFFFAOYSA-N n-[4-methyl-3-(3-piperidin-4-yl-1,2-benzoxazol-6-yl)phenyl]-2-pyrrolidin-1-ylpyridine-4-carboxamide Chemical compound C1=C(C=2C=C3ON=C(C3=CC=2)C2CCNCC2)C(C)=CC=C1NC(=O)C(C=1)=CC=NC=1N1CCCC1 DMTJDVSGJMJVRQ-UHFFFAOYSA-N 0.000 claims description 3
- KFPURLJOUSYIJO-UHFFFAOYSA-N n-cyclopropyl-3-(1-cyclopropylsulfonylindazol-5-yl)-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1CC1 KFPURLJOUSYIJO-UHFFFAOYSA-N 0.000 claims description 3
- MIKPYEYGSONYIQ-UHFFFAOYSA-N n-cyclopropyl-3-(1-cyclopropylsulfonylindazol-5-yl)-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1CC1 MIKPYEYGSONYIQ-UHFFFAOYSA-N 0.000 claims description 3
- GXQPIHVHXAQIER-UHFFFAOYSA-N n-cyclopropyl-3-(1-ethylsulfonylindazol-5-yl)-4-methylbenzamide Chemical compound C=1C=C2N(S(=O)(=O)CC)N=CC2=CC=1C(C(=CC=1)C)=CC=1C(=O)NC1CC1 GXQPIHVHXAQIER-UHFFFAOYSA-N 0.000 claims description 3
- LBELLHZXBDPQKS-UHFFFAOYSA-N n-cyclopropyl-3-(1-ethylsulfonylindazol-5-yl)-5-fluoro-4-methylbenzamide Chemical compound C=1C=C2N(S(=O)(=O)CC)N=CC2=CC=1C(C(=C(F)C=1)C)=CC=1C(=O)NC1CC1 LBELLHZXBDPQKS-UHFFFAOYSA-N 0.000 claims description 3
- GFOYQAPBQVBSJX-UHFFFAOYSA-N n-cyclopropyl-3-[1-(3-fluorophenyl)sulfonylindazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=CC(F)=C1 GFOYQAPBQVBSJX-UHFFFAOYSA-N 0.000 claims description 3
- VFVJBKOJEDWHAJ-UHFFFAOYSA-N n-cyclopropyl-3-[1-(4-fluorophenyl)sulfonylindazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=C(F)C=C1 VFVJBKOJEDWHAJ-UHFFFAOYSA-N 0.000 claims description 3
- QVYQJEUMPRLNID-UHFFFAOYSA-N n-cyclopropyl-3-[1-(cyclopropylmethyl)indazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1CC1 QVYQJEUMPRLNID-UHFFFAOYSA-N 0.000 claims description 3
- OVTXZFQGXZZQRE-UHFFFAOYSA-N n-cyclopropyl-3-[1-[(3,5-dimethyl-1,2-oxazol-4-yl)sulfonyl]indazol-5-yl]-5-fluoro-4-methylbenzamide Chemical compound CC1=NOC(C)=C1S(=O)(=O)N1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=C2C=N1 OVTXZFQGXZZQRE-UHFFFAOYSA-N 0.000 claims description 3
- VPIWRNWXHSRPLX-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-(3-methyl-1-thiophen-2-ylsulfonylindazol-5-yl)benzamide Chemical compound C1=C2C(C)=NN(S(=O)(=O)C=3SC=CC=3)C2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1CC1 VPIWRNWXHSRPLX-UHFFFAOYSA-N 0.000 claims description 3
- OUCJOAAANUQYMX-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[1-(2-fluorophenyl)sulfonylindazol-5-yl]-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1F OUCJOAAANUQYMX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- OHEDPOHRYKEJRB-UHFFFAOYSA-N n-cyclopropyl-3-[1-(2,5-difluorophenyl)sulfonylindazol-5-yl]-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2S(=O)(=O)C1=CC(F)=CC=C1F OHEDPOHRYKEJRB-UHFFFAOYSA-N 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 249
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 164
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 160
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 83
- 239000000377 silicon dioxide Substances 0.000 description 80
- 239000007787 solid Substances 0.000 description 73
- 239000002904 solvent Substances 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 55
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 54
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 239000002253 acid Substances 0.000 description 33
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 229910000029 sodium carbonate Inorganic materials 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 238000004440 column chromatography Methods 0.000 description 25
- 238000010992 reflux Methods 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 230000002209 hydrophobic effect Effects 0.000 description 16
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 235000002639 sodium chloride Nutrition 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000007821 HATU Substances 0.000 description 11
- 229910021529 ammonia Inorganic materials 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- HZKJOEBOIMSMJP-UHFFFAOYSA-N n-cyclopropyl-3-(1h-indazol-5-yl)-4-methylbenzamide Chemical compound C1=C(C=2C=C3C=NNC3=CC=2)C(C)=CC=C1C(=O)NC1CC1 HZKJOEBOIMSMJP-UHFFFAOYSA-N 0.000 description 11
- GLSSVRGOTTUQNM-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1B1OC(C)(C)C(C)(C)O1 GLSSVRGOTTUQNM-UHFFFAOYSA-N 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- NOIZJQWRHYHTSU-UHFFFAOYSA-N 6-bromo-3-piperidin-4-yl-1,2-benzoxazole Chemical compound N=1OC2=CC(Br)=CC=C2C=1C1CCNCC1 NOIZJQWRHYHTSU-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 235000011056 potassium acetate Nutrition 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 230000001684 chronic effect Effects 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- LSPSVCJKVFCWHE-UHFFFAOYSA-N 6-bromo-3-methyl-1,2-benzoxazole Chemical compound BrC1=CC=C2C(C)=NOC2=C1 LSPSVCJKVFCWHE-UHFFFAOYSA-N 0.000 description 8
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 8
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 8
- GIWCBSLJBLIGKK-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-(1h-indazol-5-yl)-4-methylbenzamide Chemical compound C1=C(C=2C=C3C=NNC3=CC=2)C(C)=C(F)C=C1C(=O)NC1CC1 GIWCBSLJBLIGKK-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 7
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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Applications Claiming Priority (2)
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|---|---|---|---|
| GB0217757 | 2002-07-31 | ||
| GBGB0217757.4A GB0217757D0 (en) | 2002-07-31 | 2002-07-31 | Novel compounds |
Publications (1)
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|---|---|
| ES2289336T3 true ES2289336T3 (es) | 2008-02-01 |
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| ES03771208T Expired - Lifetime ES2289336T3 (es) | 2002-07-31 | 2003-07-30 | Derivados heteroarilicos condensados para su uso como inhibidores de quinasa p38 en el tratamiento de, entre otras, artritis reumatoide. |
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| EP (1) | EP1531812B1 (enExample) |
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| DE (1) | DE60314639T2 (enExample) |
| ES (1) | ES2289336T3 (enExample) |
| GB (1) | GB0217757D0 (enExample) |
| WO (1) | WO2004010995A1 (enExample) |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124931D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| ATE375980T1 (de) | 2002-02-12 | 2007-11-15 | Smithkline Beecham Corp | Nicotinamide und deren verwendung als p38 inhibitoren |
| GB0209891D0 (en) | 2002-04-30 | 2002-06-05 | Glaxo Group Ltd | Novel compounds |
| GB0308201D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308186D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| JP4810427B2 (ja) * | 2003-05-22 | 2011-11-09 | アボット・ラボラトリーズ | インダゾール、ベンズイソオキサゾールおよびベンズイソチアゾールキナーゼ阻害剤 |
| US7297709B2 (en) | 2003-05-22 | 2007-11-20 | Abbott Laboratories | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| WO2005000298A2 (en) | 2003-06-03 | 2005-01-06 | Novartis Ag | 5-membered heterocycle-based p-38 inhibitors |
| CN1832928B (zh) | 2003-06-26 | 2012-07-04 | 诺瓦提斯公司 | 以5元杂环为基础的p38激酶抑制剂 |
| DE602004029293D1 (de) | 2003-07-25 | 2010-11-04 | Novartis Ag | p-38-Kinasehemmer |
| GB0318814D0 (en) * | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| GB0402140D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402137D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402138D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| US20070185152A1 (en) * | 2004-03-02 | 2007-08-09 | Smithkline Beecham Corporation | Inhibitors of akt activity |
| US20050234095A1 (en) | 2004-03-25 | 2005-10-20 | Wenge Xie | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| GB0417905D0 (en) * | 2004-08-11 | 2004-09-15 | Novartis Ag | Organic compounds |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
| US7759337B2 (en) | 2005-03-03 | 2010-07-20 | Amgen Inc. | Phthalazine compounds and methods of use |
| DE102005038947A1 (de) * | 2005-05-18 | 2006-11-30 | Grünenthal GmbH | Substituierte Benzo[d]isoxazol-3-yl-amin-Verbindungen und deren Verwendung in Arzneimitteln |
| US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
| GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
| MX2007016541A (es) * | 2005-06-30 | 2008-03-07 | Smithkline Beecham Corp | Compuestos quimicos. |
| AU2007240568A1 (en) | 2006-04-21 | 2007-11-01 | Amgen Inc. | Thieno-[2,3-d]pyrimidine and thieno-pyridazine compounds and methods of use |
| GB0612026D0 (en) | 2006-06-16 | 2006-07-26 | Smithkline Beecham Corp | New use |
| ES2301380B1 (es) | 2006-08-09 | 2009-06-08 | Laboratorios Almirall S.A. | Nuevos derivados de 1,7-naftiridina. |
| AU2007293065B2 (en) | 2006-09-05 | 2011-08-18 | Amgen Inc. | Phthalazine, AZA- and diaza-phthalazine compounds and methods of use |
| ES2377821T3 (es) * | 2006-10-11 | 2012-04-02 | Amgen Inc. | Compuestos de imidazo- y triazolo-piridina y métodos de uso de los mismos. |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| ES2329639B1 (es) | 2007-04-26 | 2010-09-23 | Laboratorios Almirall S.A. | Nuevos derivados de 4,8-difenilpoliazanaftaleno. |
| CA2685597C (en) | 2007-05-07 | 2012-10-02 | Amgen Inc. | Pyrazolo-pyridinone and pyrazolo-pyrazinone compounds as p38 modulators, process for their preparation, and their pharmaceutical use |
| CA2685674C (en) | 2007-05-07 | 2012-07-17 | Amgen Inc. | Pyrazolo-pyridinone compounds, process for their preparation, and their pharmaceutical use |
| ES2401557T3 (es) * | 2007-08-02 | 2013-04-22 | Amgen, Inc | Moduladores de Pl3 cinasas y métodos de uso |
| WO2009038784A1 (en) * | 2007-09-21 | 2009-03-26 | Amgen Inc. | Triazole fused heteroaryl compounds as p38 kinase inhibitors |
| WO2009078992A1 (en) * | 2007-12-17 | 2009-06-25 | Amgen Inc. | Linear tricyclic compounds as p38 kinase inhibitors |
| US7820665B2 (en) | 2007-12-19 | 2010-10-26 | Amgen Inc. | Imidazopyridazine inhibitors of PI3 kinase for cancer treatment |
| US8367671B2 (en) | 2008-03-21 | 2013-02-05 | Amgen Inc. | Pyrazolo[3.4-B]pyrazine compounds as p38 modulators and methods of use as anti-inflamatory agents |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| AU2009241038B2 (en) | 2008-04-28 | 2011-12-22 | Asahi Kasei Pharma Corporation | Phenylpropionic acid derivative and use thereof |
| WO2009152356A2 (en) * | 2008-06-11 | 2009-12-17 | Irm Llc | Compounds and compositions useful for the treatment of malaria |
| JP2011525535A (ja) * | 2008-06-24 | 2011-09-22 | 武田薬品工業株式会社 | PI3K/mTOR阻害剤 |
| EP2334673A1 (en) | 2008-08-29 | 2011-06-22 | Amgen Inc. | PYRIDO[3,2-d]PYRIDAZINE-2(1H)-ONE COMPOUNDS AS P38 MODULATORS AND METHODS OF USE THEREOF |
| US8455495B2 (en) | 2008-08-29 | 2013-06-04 | Amgen Inc. | Pyridazino-pyridinone compounds and methods of use |
| WO2010042649A2 (en) | 2008-10-10 | 2010-04-15 | Amgen Inc. | PHTHALAZINE COMPOUNDS AS p38 MAP KINASE MODULATORS AND METHODS OF USE THEREOF |
| WO2010042646A1 (en) | 2008-10-10 | 2010-04-15 | Amgen Inc. | Aza- and diaza-phthalazine compounds as p38 map kinase modulators and methods of use thereof |
| US8969350B2 (en) * | 2008-12-18 | 2015-03-03 | Astrazeneca Ab | Pharmaceutical product comprising a p38 kinase inhibitor and a second active ingredient |
| EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
| AU2010343102B2 (en) | 2009-12-29 | 2016-03-24 | Dana-Farber Cancer Institute, Inc. | Type II Raf kinase inhibitors |
| MX2012010617A (es) * | 2010-03-16 | 2012-10-05 | Dana Farber Cancer Inst Inc | Compuestos de imidazol y sus usos. |
| JPWO2012086735A1 (ja) * | 2010-12-22 | 2014-06-05 | 大正製薬株式会社 | 縮合複素環化合物 |
| CN102617548A (zh) * | 2011-01-31 | 2012-08-01 | 北京赛林泰医药技术有限公司 | 作为gpr受体激动剂的双环杂芳基化合物及其组合物和应用 |
| JP6106685B2 (ja) | 2011-11-17 | 2017-04-05 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | C−jun−n−末端キナーゼ(jnk)の阻害剤 |
| US10112927B2 (en) | 2012-10-18 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| WO2014063061A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| WO2014063054A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Bone marrow on x chromosome kinase (bmx) inhibitors and uses thereof |
| EP3057956B1 (en) | 2013-10-18 | 2021-05-05 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
| EP3057955B1 (en) | 2013-10-18 | 2018-04-11 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
| WO2015164614A1 (en) | 2014-04-23 | 2015-10-29 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
| US9862688B2 (en) | 2014-04-23 | 2018-01-09 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
| CA2972239A1 (en) | 2014-12-23 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| CN107427521B (zh) | 2015-03-27 | 2021-08-03 | 达纳-法伯癌症研究所股份有限公司 | 细胞周期蛋白依赖性激酶的抑制剂 |
| WO2016201370A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| CN105085427B (zh) * | 2015-08-21 | 2018-06-05 | 中国科学院广州生物医药与健康研究院 | 一类苯并[d]异恶唑类化合物及其应用 |
| EP4019515A1 (en) | 2015-09-09 | 2022-06-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| EP3357916A4 (en) * | 2015-09-30 | 2019-06-26 | CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. | benzamide |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| CA3127373A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce dux4 and downstream gene expression for the treatment of fshd |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| EP3773579A4 (en) | 2018-03-26 | 2022-03-09 | Clear Creek Bio, Inc. | COMPOSITIONS AND METHODS FOR INHIBITING DIHYDROOROTATE DEHYDROGENASE |
| JP7590185B2 (ja) | 2018-06-25 | 2024-11-26 | ダナ-ファーバー キャンサー インスティテュート, インコーポレイテッド | Taireファミリーキナーゼインヒビターおよびそれらの使用 |
| EP3902542A4 (en) | 2018-12-28 | 2022-09-07 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 and uses thereof |
| US12076315B2 (en) | 2020-03-20 | 2024-09-03 | Clear Creek Bio, Inc. | Stable polymorphic compositions of brequinar sodium and methods of use and manufacture thereof |
Family Cites Families (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4200750A (en) | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| DE3919348A1 (de) | 1988-06-16 | 1989-12-21 | Ciba Geigy Ag | Mikrobizide mittel |
| MX16687A (es) | 1988-07-07 | 1994-01-31 | Ciba Geigy Ag | Compuestos de biarilo y procedimiento para su preparacion. |
| EP0430033A3 (en) | 1989-11-24 | 1991-09-11 | Ciba-Geigy Ag | Microbicidal agents |
| DE69232003T2 (de) | 1991-09-18 | 2002-04-25 | Glaxo Group Ltd., Greenford | Benzanilidderivate als 5-HT1D-Antagonisten |
| GB9816837D0 (en) | 1998-08-04 | 1998-09-30 | Zeneca Ltd | Amide derivatives |
| US5246943A (en) | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
| US5236934A (en) | 1992-08-26 | 1993-08-17 | E. I. Du Pont De Nemours And Company | 1,2,3,4-tetrahydroisoquinolines useful in the treatment of CNS disorders |
| TW240217B (enExample) | 1992-12-30 | 1995-02-11 | Glaxo Group Ltd | |
| GB2273930A (en) | 1992-12-30 | 1994-07-06 | Glaxo Group Ltd | Benzanilide derivatives |
| IL108630A0 (en) | 1993-02-18 | 1994-05-30 | Fmc Corp | Insecticidal substituted 2,4-diaminoquinazolines |
| GB2276161A (en) | 1993-03-17 | 1994-09-21 | Glaxo Group Ltd | Aniline and benzanilide derivatives |
| WO1995006644A1 (en) | 1993-09-03 | 1995-03-09 | Smithkline Beecham Plc | Amide derivatives as 5ht1d receptor antagonists |
| JPH09503773A (ja) | 1993-10-19 | 1997-04-15 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5ht−1dレセプター拮抗剤用のベンズアニリド誘導体 |
| AU1108395A (en) | 1993-12-07 | 1995-06-27 | Smithkline Beecham Plc | Heterocyclic biphenylylamides useful as 5ht1d antagonists |
| GB9326008D0 (en) | 1993-12-21 | 1994-02-23 | Smithkline Beecham Plc | Novel compounds |
| GB9408577D0 (en) | 1994-04-29 | 1994-06-22 | Fujisawa Pharmaceutical Co | New compound |
| JPH09512804A (ja) | 1994-05-06 | 1997-12-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5−ht1dアンタゴニストとして有用なビフェニルカルボキシアミド類 |
| US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| GB2295387A (en) | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
| SK133297A3 (en) | 1995-04-04 | 1998-07-08 | Glaxo Group Ltd | Imidazo[1,2-a]pyridine derivatives, pharmaceutical composition containing same and their use |
| GB9507203D0 (en) | 1995-04-07 | 1995-05-31 | Smithkline Beecham Plc | Novel compounds |
| IL118544A (en) | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| AU709961B2 (en) | 1995-07-10 | 1999-09-09 | Dow Chemical Company, The | Polynitrile oxides |
| CA2502764A1 (en) | 1995-08-22 | 1997-03-06 | Japan Tobacco Inc. | Amide compounds |
| US6080767A (en) | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US6323227B1 (en) | 1996-01-02 | 2001-11-27 | Aventis Pharmaceuticals Products Inc. | Substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| NZ327044A (en) | 1996-01-11 | 2000-01-28 | Smithkline Beecham Corp | Substituted imidazole compounds |
| FR2754260B1 (fr) | 1996-10-04 | 1998-10-30 | Adir | Nouveaux derives substitues de biphenyle ou de phenylpyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US5945418A (en) | 1996-12-18 | 1999-08-31 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US6147080A (en) | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US6087496A (en) | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| PL336990A1 (en) | 1997-05-22 | 2000-07-31 | Searle & Co | 3(5)-heteroaryl group substituted pyrazoles as inhibitors of kinase p 38 |
| WO1998056377A1 (en) | 1997-06-13 | 1998-12-17 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| AU7976998A (en) | 1997-06-19 | 1999-01-04 | Du Pont Merck Pharmaceutical Company, The | (amidino)6-membered aromatics as factor xa inhibitors |
| US6060491A (en) | 1997-06-19 | 2000-05-09 | Dupont Pharmaceuticals | 6-membered aromatics as factor Xa inhibitors |
| EP1019396A1 (en) | 1997-07-02 | 2000-07-19 | SmithKline Beecham Corporation | Novel cycloalkyl substituted imidazoles |
| ATE281458T1 (de) | 1997-09-05 | 2004-11-15 | Glaxo Group Ltd | Pharmazeutische zusammensetzung, enthaltend 2,3- diaryl-pyrazolo(1,5-b)pyridazin derivate |
| AU735737B2 (en) | 1997-10-14 | 2001-07-12 | Asahi Kasei Kabushiki Kaisha | Biphenyl-5-alkanoic acid derivatives and use thereof |
| EP1042305B1 (en) | 1997-12-22 | 2005-06-08 | Bayer Pharmaceuticals Corp. | INHIBITION OF p38 KINASE USING SYMMETRICAL AND UNSYMMETRICAL DIPHENYL UREAS |
| JPH11218884A (ja) | 1998-02-03 | 1999-08-10 | Konica Corp | ハロゲン化銀写真感光材料 |
| DE19817461A1 (de) | 1998-04-20 | 1999-10-21 | Basf Ag | Neue substituierte Benzamide, deren Herstellung und Anwendung |
| ES2232137T3 (es) | 1998-05-15 | 2005-05-16 | Astrazeneca Ab | Derivados de benzamida para el tratamiento de enfermedades mediadas por citoquinas. |
| US6448257B1 (en) | 1998-05-22 | 2002-09-10 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6130235A (en) | 1998-05-22 | 2000-10-10 | Scios Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6867209B1 (en) | 1998-05-22 | 2005-03-15 | Scios, Inc. | Indole-type derivatives as inhibitors of p38 kinase |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| EP1107758A2 (en) | 1998-08-28 | 2001-06-20 | Scios Inc. | Use of piperidines and/or piperazines as inhibitors of p38-alpha kinase |
| AU762245B2 (en) | 1998-09-18 | 2003-06-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| EP1140840B1 (en) | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| AU4166400A (en) | 1999-02-11 | 2000-08-29 | Cor Therapeutics, Inc. | Alkenyl and alkynyl compounds as inhibitors of factor xa |
| ATE261444T1 (de) | 1999-02-27 | 2004-03-15 | Glaxo Group Ltd | Pyrazolopyridine |
| GB9906566D0 (en) | 1999-03-23 | 1999-05-19 | Zeneca Ltd | Chemical compounds |
| US6509361B1 (en) | 1999-05-12 | 2003-01-21 | Pharmacia Corporation | 1,5-Diaryl substituted pyrazoles as p38 kinase inhibitors |
| JP2003500387A (ja) | 1999-05-24 | 2003-01-07 | シーオーアール セラピューティクス インコーポレイテッド | Xa因子の阻害剤 |
| AU5723500A (en) | 1999-05-24 | 2000-12-12 | Cor Therapeutics, Inc. | Inhibitors of factor xa |
| WO2000071507A2 (en) | 1999-05-24 | 2000-11-30 | Cor Therapeutics, Inc. | INHIBITORS OF FACTOR Xa |
| DE19932571A1 (de) | 1999-07-13 | 2001-01-18 | Clariant Gmbh | Verfahren zur Herstellung von Biarylen unter Palladophosphacyclobutan-Katalyse |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| US6576632B1 (en) | 1999-08-27 | 2003-06-10 | Pfizer Inc | Biaryl compounds useful as anticancer agents |
| GB9924092D0 (en) | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
| WO2001070695A1 (en) | 2000-03-22 | 2001-09-27 | Vertex Pharmaceuticals Incorporated | Pyridine derivatives as inhibitors of p38 |
| PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| JPWO2002029720A1 (ja) | 2000-09-29 | 2004-02-12 | 中央発條株式会社 | 指紋照合装置及び指紋照合方法 |
| EE200300227A (et) | 2000-11-17 | 2003-10-15 | Bristol-Myers Squibb Company | P38 kinaasiga seotud haigusseisundite ravimeetodid ja kinaasi inhibiitoritena kasulikud pürrolotriasiiniühendid |
| DE10059418A1 (de) | 2000-11-30 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, meta-substituierte Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10060807A1 (de) | 2000-12-07 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, ortho-substituierte stickstoffhaltige Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10063008A1 (de) | 2000-12-16 | 2002-06-20 | Merck Patent Gmbh | Carbonsäureamidderivate |
| CA2432114A1 (en) * | 2000-12-20 | 2002-07-18 | Sugen, Inc. | 4-(hetero)aryl substituted indolinones |
| DE10110749A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| CN1496366A (zh) | 2001-03-09 | 2004-05-12 | �Ʒ� | 作为抗炎剂的三唑并吡啶 |
| ES2332090T3 (es) | 2001-04-06 | 2010-01-26 | Biocryst Pharmaceuticals, Inc. | Compuestos biarilicos como inhibidores de serina proteasa. |
| FR2824827B1 (fr) | 2001-05-17 | 2004-02-13 | Fournier Lab Sa | Nouveaux derives de 5-phenyl-1h-indole antagoniste des recepteurs de l'interleukine-8 |
| AR037233A1 (es) | 2001-09-07 | 2004-11-03 | Euro Celtique Sa | Piridinas aril sustituidas, composiciones farmaceuticas y el uso de dichos compuestos para la elaboracion de un medicamento |
| GB0124848D0 (en) | 2001-10-16 | 2001-12-05 | Celltech R&D Ltd | Chemical compounds |
| GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124936D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124932D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| ATE375980T1 (de) | 2002-02-12 | 2007-11-15 | Smithkline Beecham Corp | Nicotinamide und deren verwendung als p38 inhibitoren |
| US20030225089A1 (en) | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
| GB0209891D0 (en) | 2002-04-30 | 2002-06-05 | Glaxo Group Ltd | Novel compounds |
| ES2411655T3 (es) * | 2002-05-17 | 2013-07-08 | Pfizer Italia S.R.L. | Derivados de aminoindazol activos como inhibidores de quinasas, procedimiento para su preparación y composiciones farmacéuticas que los comprenden |
| US20040110802A1 (en) * | 2002-08-23 | 2004-06-10 | Atli Thorarensen | Antibacterial benzoic acid derivatives |
| US20040116479A1 (en) | 2002-10-04 | 2004-06-17 | Fortuna Haviv | Method of inhibiting angiogenesis |
| WO2004080996A1 (en) | 2003-03-07 | 2004-09-23 | Eli Lilly And Company | Opioid receptor antagonists |
| GB0308186D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308185D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308201D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| DE602004029293D1 (de) | 2003-07-25 | 2010-11-04 | Novartis Ag | p-38-Kinasehemmer |
| GB0318814D0 (en) | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| GB0402140D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402137D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402138D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| US20080051416A1 (en) | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
-
2002
- 2002-07-31 GB GBGB0217757.4A patent/GB0217757D0/en not_active Ceased
-
2003
- 2003-07-30 ES ES03771208T patent/ES2289336T3/es not_active Expired - Lifetime
- 2003-07-30 AU AU2003248978A patent/AU2003248978A1/en not_active Abandoned
- 2003-07-30 AT AT03771208T patent/ATE365551T1/de not_active IP Right Cessation
- 2003-07-30 DE DE60314639T patent/DE60314639T2/de not_active Expired - Lifetime
- 2003-07-30 JP JP2004523985A patent/JP4630662B2/ja not_active Expired - Fee Related
- 2003-07-30 WO PCT/GB2003/003316 patent/WO2004010995A1/en not_active Ceased
- 2003-07-30 US US10/522,955 patent/US7642276B2/en not_active Expired - Fee Related
- 2003-07-30 EP EP03771208A patent/EP1531812B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US7642276B2 (en) | 2010-01-05 |
| EP1531812A1 (en) | 2005-05-25 |
| DE60314639D1 (de) | 2007-08-09 |
| GB0217757D0 (en) | 2002-09-11 |
| WO2004010995A1 (en) | 2004-02-05 |
| DE60314639T2 (de) | 2008-03-13 |
| JP4630662B2 (ja) | 2011-02-09 |
| JP2005538100A (ja) | 2005-12-15 |
| EP1531812B1 (en) | 2007-06-27 |
| ATE365551T1 (de) | 2007-07-15 |
| US20060122221A1 (en) | 2006-06-08 |
| AU2003248978A1 (en) | 2004-02-16 |
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