ES2290486T3 - Derivados de bifenilo sustituidos con heteroarilo como inhibidores de la quinasa p38. - Google Patents
Derivados de bifenilo sustituidos con heteroarilo como inhibidores de la quinasa p38. Download PDFInfo
- Publication number
- ES2290486T3 ES2290486T3 ES03747504T ES03747504T ES2290486T3 ES 2290486 T3 ES2290486 T3 ES 2290486T3 ES 03747504 T ES03747504 T ES 03747504T ES 03747504 T ES03747504 T ES 03747504T ES 2290486 T3 ES2290486 T3 ES 2290486T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- biphenyl
- oxadiazol
- cyclopropyl
- carboxamide
- 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
Links
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 21
- 150000002367 halogens Chemical class 0.000 claims abstract description 21
- 229910052717 sulfur Chemical group 0.000 claims abstract description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 239000001301 oxygen Substances 0.000 claims abstract description 20
- 239000011593 sulfur Chemical group 0.000 claims abstract description 20
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000460 chlorine Chemical group 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 3
- -1 CONHR 12 Chemical group 0.000 claims description 111
- 239000000203 mixture Substances 0.000 claims description 52
- 239000002253 acid Substances 0.000 claims description 51
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 34
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 claims description 12
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical group [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 239000003981 vehicle Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- OSITVSIIJTXZAS-UHFFFAOYSA-N 3-[4-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CN)O1 OSITVSIIJTXZAS-UHFFFAOYSA-N 0.000 claims description 6
- ZJWLMZURLIHVHE-UHFFFAOYSA-N 3-morpholin-4-ylaniline Chemical compound NC1=CC=CC(N2CCOCC2)=C1 ZJWLMZURLIHVHE-UHFFFAOYSA-N 0.000 claims description 6
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- QUKGLNCXGVWCJX-UHFFFAOYSA-N 1,3,4-thiadiazol-2-amine Chemical compound NC1=NN=CS1 QUKGLNCXGVWCJX-UHFFFAOYSA-N 0.000 claims description 5
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 5
- DCGLVCMJNRMULJ-UHFFFAOYSA-N 3-[4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(N)O1 DCGLVCMJNRMULJ-UHFFFAOYSA-N 0.000 claims description 5
- 108090000695 Cytokines Proteins 0.000 claims description 5
- 102000004127 Cytokines Human genes 0.000 claims description 5
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- AHIYPZUSTXIPAS-UHFFFAOYSA-N 3-[4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(N)O1 AHIYPZUSTXIPAS-UHFFFAOYSA-N 0.000 claims description 4
- HULVUJNICBFQPK-UHFFFAOYSA-N 3-[4-[5-[(benzylsulfonylamino)methyl]-1,3,4-oxadiazol-2-yl]phenyl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CNS(=O)(=O)CC1=CC=CC=C1 HULVUJNICBFQPK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- YLCPHCGGXXXHRD-UHFFFAOYSA-N n-cyclopropyl-3-[4-(5-ethyl-1,3,4-oxadiazol-2-yl)phenyl]-4-methylbenzamide Chemical compound O1C(CC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 YLCPHCGGXXXHRD-UHFFFAOYSA-N 0.000 claims description 4
- MXBHVZATTLYLSM-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(cyclopropylmethoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1COCC1CC1 MXBHVZATTLYLSM-UHFFFAOYSA-N 0.000 claims description 4
- FHBVQIRYGQHIBT-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(cyclopropylmethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CC1CC1 FHBVQIRYGQHIBT-UHFFFAOYSA-N 0.000 claims description 4
- LZSQWIZSJZDBPB-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(diethylaminomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound O1C(CN(CC)CC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 LZSQWIZSJZDBPB-UHFFFAOYSA-N 0.000 claims description 4
- FGTLAEHJYMELJJ-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(ethoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound O1C(COCC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 FGTLAEHJYMELJJ-UHFFFAOYSA-N 0.000 claims description 4
- OYRHQEYMYFLPAO-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(ethylaminomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound O1C(CNCC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 OYRHQEYMYFLPAO-UHFFFAOYSA-N 0.000 claims description 4
- VSRUWPKXKDSOOQ-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(methanesulfonamidomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CNS(C)(=O)=O)O1 VSRUWPKXKDSOOQ-UHFFFAOYSA-N 0.000 claims description 4
- QWAVSMHEVGAMTB-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound O1C(COC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 QWAVSMHEVGAMTB-UHFFFAOYSA-N 0.000 claims description 4
- LGBSXTHUMXGOSO-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-[(3,3-dimethylbutanoylamino)methyl]-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CNC(=O)CC(C)(C)C)O1 LGBSXTHUMXGOSO-UHFFFAOYSA-N 0.000 claims description 4
- MBGPKRGRECBFQQ-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-[(cyclopropylamino)methyl]-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CNC1CC1 MBGPKRGRECBFQQ-UHFFFAOYSA-N 0.000 claims description 4
- CZZJHSKQVNDTIZ-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-[(cyclopropylamino)methyl]-1,3,4-oxadiazol-2-yl]phenyl]-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CNC1CC1 CZZJHSKQVNDTIZ-UHFFFAOYSA-N 0.000 claims description 4
- ISWCHSPFRNBRLW-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]benzamide Chemical compound O1C(C)=NN=C1C1=CC=C(C=2C(=C(F)C=C(C=2)C(=O)NC2CC2)C)C=C1 ISWCHSPFRNBRLW-UHFFFAOYSA-N 0.000 claims description 4
- DWANNDBUEPOVCV-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[4-[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound O1C(COC)=NN=C1C1=CC=C(C=2C(=C(F)C=C(C=2)C(=O)NC2CC2)C)C=C1 DWANNDBUEPOVCV-UHFFFAOYSA-N 0.000 claims description 4
- GHDOOBTTWRGZFE-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[4-(1,3,4-oxadiazol-2-yl)phenyl]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=CO1 GHDOOBTTWRGZFE-UHFFFAOYSA-N 0.000 claims description 4
- YMERFPDLXSRENN-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[4-[5-(1-methylpyrrol-2-yl)-1,3,4-oxadiazol-2-yl]phenyl]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1C1=CC=CN1C YMERFPDLXSRENN-UHFFFAOYSA-N 0.000 claims description 4
- DGNKXPYLGHSCLU-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[4-[5-(methylamino)-1,3,4-oxadiazol-2-yl]phenyl]benzamide Chemical compound O1C(NC)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C=C1 DGNKXPYLGHSCLU-UHFFFAOYSA-N 0.000 claims description 4
- HOHZBOGLXKHQJH-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[4-[5-(thiomorpholin-4-ylmethyl)-1,3,4-oxadiazol-2-yl]phenyl]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CN1CCSCC1 HOHZBOGLXKHQJH-UHFFFAOYSA-N 0.000 claims description 4
- AWMNVQSGOCRGQW-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[4-[5-[[(2-phenylacetyl)amino]methyl]-1,3,4-oxadiazol-2-yl]phenyl]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C(O1)=NN=C1CNC(=O)CC1=CC=CC=C1 AWMNVQSGOCRGQW-UHFFFAOYSA-N 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- UBVTVSINEVHYSY-UHFFFAOYSA-N N-cyclopropyl-2',6-dimethyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-3-carboxamide Chemical group O1C(C)=NN=C1C1=CC=C(C=2C(=CC=C(C=2)C(=O)NC2CC2)C)C(C)=C1 UBVTVSINEVHYSY-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- DCBSFPVMMSHESN-UHFFFAOYSA-N n-cyclopropyl-3-[4-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CO)O1 DCBSFPVMMSHESN-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 229910052770 Uranium Inorganic materials 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YJEKRWXNGQEKFK-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[4-(2h-tetrazol-5-yl)phenyl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=NN1 YJEKRWXNGQEKFK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 324
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 178
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 165
- 239000002904 solvent Substances 0.000 description 122
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 119
- 230000014759 maintenance of location Effects 0.000 description 118
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 111
- 238000006243 chemical reaction Methods 0.000 description 106
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 239000000377 silicon dioxide Substances 0.000 description 80
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- 239000000047 product Substances 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 39
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 34
- 239000012074 organic phase Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 238000001704 evaporation Methods 0.000 description 26
- 230000008020 evaporation Effects 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- IHBPTBQXHHHEOU-UHFFFAOYSA-N 3-[4-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CN)O1 IHBPTBQXHHHEOU-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 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 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000007821 HATU Substances 0.000 description 14
- 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 14
- 235000002639 sodium chloride Nutrition 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- RETOXUZMRNTMFR-UHFFFAOYSA-N 3-[4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]phenyl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1)=CC=C1C1=NN=C(CCl)O1 RETOXUZMRNTMFR-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
- FDGZZTICDKUCIA-UHFFFAOYSA-N sodium;cyclopropylmethanolate Chemical compound [Na+].[O-]CC1CC1 FDGZZTICDKUCIA-UHFFFAOYSA-N 0.000 description 1
- AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
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- 201000004595 synovitis Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 1
- IWVWZOSJDHVNSZ-UHFFFAOYSA-N tert-butyl n-[[4-[5-(cyclopropylcarbamoyl)-2-methylphenyl]benzoyl]amino]carbamate Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C1=CC=C(C(=O)NNC(=O)OC(C)(C)C)C=C1 IWVWZOSJDHVNSZ-UHFFFAOYSA-N 0.000 description 1
- IFYTZIOLHLHTEH-UHFFFAOYSA-N tert-butyl n-[[4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]benzoyl]amino]carbamate Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C1=CC=C(C(=O)NNC(=O)OC(C)(C)C)C=C1 IFYTZIOLHLHTEH-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
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- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
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- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Health & Medical Sciences (AREA)
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| GB0209891 | 2002-04-30 | ||
| GBGB0209891.1A GB0209891D0 (en) | 2002-04-30 | 2002-04-30 | Novel compounds |
Publications (1)
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|---|---|
| ES2290486T3 true ES2290486T3 (es) | 2008-02-16 |
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| ES (1) | ES2290486T3 (enExample) |
| GB (1) | GB0209891D0 (enExample) |
| WO (1) | WO2003093248A1 (enExample) |
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| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
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| GB0124931D0 (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 |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | 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 |
| GB0308186D0 (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 |
| GB0402138D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402140D0 (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 |
| GB0402137D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| US7683097B2 (en) * | 2004-05-27 | 2010-03-23 | Propharmacon Inc. | Topoisomerase inhibitors |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
| ATE502025T1 (de) * | 2004-10-19 | 2011-04-15 | Compass Pharmaceuticals Llc | Arylcarboxamide und ihre verwendung als antitumormittel |
| KR101328273B1 (ko) | 2004-12-28 | 2013-11-14 | 키넥스 파마슈티컬즈, 엘엘씨 | 세포 증식 질환의 치료를 위한 조성물 및 방법 |
| US7968574B2 (en) | 2004-12-28 | 2011-06-28 | Kinex Pharmaceuticals, Llc | Biaryl compositions and methods for modulating a kinase cascade |
| GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
| DK1940786T3 (da) * | 2005-09-16 | 2010-11-08 | Arrow Therapeutics Ltd | Biphenylderivater og deres anvendelse ved behandling af hepatitis C |
| GB0612026D0 (en) | 2006-06-16 | 2006-07-26 | Smithkline Beecham Corp | New use |
| JP5564251B2 (ja) | 2006-06-29 | 2014-07-30 | キネックス ファーマシューティカルズ, エルエルシー | キナーゼカスケードを調節するためのビアリール組成物および方法 |
| SI2511301T1 (en) | 2006-08-04 | 2018-05-31 | MedImmune Limited, | Human antibodies to ERBB 2 |
| US7939529B2 (en) | 2007-05-17 | 2011-05-10 | Kinex Pharmaceuticals, Llc | Process for the preparation of compositions for modulating a kinase cascade and methods of use thereof |
| US7935697B2 (en) | 2006-12-28 | 2011-05-03 | Kinex Pharmaceuticals, Llc | Compositions for modulating a kinase cascade and methods of use thereof |
| US8124605B2 (en) | 2007-07-06 | 2012-02-28 | Kinex Pharmaceuticals, Llc | Compositions and methods for modulating a kinase cascade |
| CN104644639A (zh) * | 2007-10-20 | 2015-05-27 | 金克斯医药品有限公司 | 用于调控激酶级联的药物组合物及其使用方法 |
| TWI490214B (zh) | 2008-05-30 | 2015-07-01 | 艾德克 上野股份有限公司 | 苯或噻吩衍生物及該等作為vap-1抑制劑之用途 |
| CA2728769A1 (en) * | 2008-07-04 | 2010-01-07 | Bruno Villoutreix | Nitrogen heterocycle derivatives as proteasome modulators |
| US8748423B2 (en) | 2010-04-16 | 2014-06-10 | Kinex Pharmaceuticals, Llc | Compositions and methods for the prevention and treatment of cancer |
| PH12013501268A1 (en) | 2010-12-17 | 2016-04-01 | Mitsubishi Tanabe Pharma Corp | Continuous arycyclic compound |
| WO2013187496A1 (ja) | 2012-06-15 | 2013-12-19 | 田辺三菱製薬株式会社 | 芳香族複素環化合物 |
| CA2883144C (en) | 2012-08-30 | 2023-01-17 | Kinex Pharmaceuticals, Llc | N-(3-fluorobenzyl)-2-(5-(4-morpholinophenyl)pyridin-2-yl) acetamide as protein|tyrosine kinase modulators |
| WO2014121055A2 (en) * | 2013-02-04 | 2014-08-07 | Janssen Pharmaceutica Nv | Flap modulators |
| TWI644899B (zh) | 2013-02-04 | 2018-12-21 | 健生藥品公司 | Flap調節劑 |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| 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 |
| 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 |
| EP3773579A4 (en) | 2018-03-26 | 2022-03-09 | Clear Creek Bio, Inc. | COMPOSITIONS AND METHODS FOR INHIBITING DIHYDROOROTATE DEHYDROGENASE |
| 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 (17)
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| TW240217B (enExample) * | 1992-12-30 | 1995-02-11 | Glaxo Group Ltd | |
| AU1108395A (en) * | 1993-12-07 | 1995-06-27 | Smithkline Beecham Plc | Heterocyclic biphenylylamides useful as 5ht1d antagonists |
| ES2179254T3 (es) * | 1996-11-04 | 2003-01-16 | Bayer Cropscience Sa | 1-poliarilpirazoles plaguicidas. |
| PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| GB0119863D0 (en) * | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| 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 |
| 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 |
| 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 |
| GB0124928D0 (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 |
| GB0209891D0 (en) | 2002-04-30 | 2002-06-05 | Glaxo Group Ltd | Novel compounds |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
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2002
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2003
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- 2003-04-29 EP EP03747504A patent/EP1499600B1/en not_active Expired - Lifetime
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- 2003-04-29 AT AT03747504T patent/ATE368034T1/de not_active IP Right Cessation
- 2003-04-29 AU AU2003226572A patent/AU2003226572A1/en not_active Abandoned
Also Published As
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| GB0209891D0 (en) | 2002-06-05 |
| WO2003093248A1 (en) | 2003-11-13 |
| EP1499600B1 (en) | 2007-07-25 |
| DE60315146D1 (de) | 2007-09-06 |
| AU2003226572A1 (en) | 2003-11-17 |
| DE60315146T2 (de) | 2008-04-17 |
| US7425555B2 (en) | 2008-09-16 |
| ATE368034T1 (de) | 2007-08-15 |
| US20060089393A1 (en) | 2006-04-27 |
| EP1499600A1 (en) | 2005-01-26 |
| JP2005535586A (ja) | 2005-11-24 |
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