BRPI0707719A2 - uso de um composto ou de um sal farmaceuticamente aceitÁvel do mesmo - Google Patents
uso de um composto ou de um sal farmaceuticamente aceitÁvel do mesmo Download PDFInfo
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- BRPI0707719A2 BRPI0707719A2 BRPI0707719-0A BRPI0707719A BRPI0707719A2 BR PI0707719 A2 BRPI0707719 A2 BR PI0707719A2 BR PI0707719 A BRPI0707719 A BR PI0707719A BR PI0707719 A2 BRPI0707719 A2 BR PI0707719A2
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 263
- 150000003839 salts Chemical class 0.000 title claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 1154
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 62
- 125000003118 aryl group Chemical group 0.000 claims abstract description 54
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 32
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 30
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 28
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims abstract description 22
- 125000001424 substituent group Chemical group 0.000 claims abstract description 22
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
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- 125000005647 linker group Chemical group 0.000 claims abstract description 8
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 8
- 125000003435 aroyl group Chemical group 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 6
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- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 74
- -1 fiirane Natural products 0.000 claims description 59
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 47
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
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- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 29
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- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 229920006395 saturated elastomer Polymers 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 11
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- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000005000 thioaryl group Chemical group 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 7
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- 125000001544 thienyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- 125000004001 thioalkyl group Chemical group 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- 125000004450 alkenylene group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004419 alkynylene group Chemical group 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 2
- 201000006935 Becker muscular dystrophy Diseases 0.000 claims 1
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1366
- 238000005160 1H NMR spectroscopy Methods 0.000 description 468
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 437
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
- 238000000034 method Methods 0.000 description 123
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
- 239000012044 organic layer Substances 0.000 description 64
- 239000000203 mixture Substances 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 239000007787 solid Substances 0.000 description 39
- 238000004440 column chromatography Methods 0.000 description 35
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 35
- 235000019341 magnesium sulphate Nutrition 0.000 description 35
- 125000005605 benzo group Chemical group 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 32
- 238000001816 cooling Methods 0.000 description 30
- 238000010828 elution Methods 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
- 238000007429 general method Methods 0.000 description 22
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
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- 239000002253 acid Substances 0.000 description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 210000003205 muscle Anatomy 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 102000011856 Utrophin Human genes 0.000 description 11
- 108010075653 Utrophin Proteins 0.000 description 11
- 229940047889 isobutyramide Drugs 0.000 description 11
- 239000007821 HATU Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 108010069091 Dystrophin Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- QWTDNUCVQCZILF-UHFFFAOYSA-N iso-pentane Natural products CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 8
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- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000001039 Dystrophin Human genes 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 238000009739 binding Methods 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 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 7
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- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- SUOXXPHZWVBJSY-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazol-5-amine Chemical compound N=1C2=CC(N)=CC=C2OC=1C1=CC=CC=C1 SUOXXPHZWVBJSY-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000463 material Substances 0.000 description 5
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- 239000008194 pharmaceutical composition Substances 0.000 description 5
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- 230000008569 process Effects 0.000 description 5
- 150000000183 1,3-benzoxazoles Chemical class 0.000 description 4
- YBEAMOBHNFDQMM-UHFFFAOYSA-N 1,3-oxazol-5-amine Chemical compound NC1=CN=CO1 YBEAMOBHNFDQMM-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 0 CCSCCCC*C(CN)[C@](C)*C Chemical compound CCSCCCC*C(CN)[C@](C)*C 0.000 description 4
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- APEJMQOBVMLION-UHFFFAOYSA-N cinnamamide Chemical compound NC(=O)C=CC1=CC=CC=C1 APEJMQOBVMLION-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 229910000365 copper sulfate Inorganic materials 0.000 description 4
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 4
- 238000011161 development Methods 0.000 description 4
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- 230000000144 pharmacologic effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
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- 238000011282 treatment Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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- HSZLOKDLSZAZCH-UHFFFAOYSA-N 2-(4-methylphenyl)-1,3-benzoxazol-5-amine Chemical compound C1=CC(C)=CC=C1C1=NC2=CC(N)=CC=C2O1 HSZLOKDLSZAZCH-UHFFFAOYSA-N 0.000 description 3
- VLZVIIYRNMWPSN-UHFFFAOYSA-N 2-Amino-4-nitrophenol Chemical compound NC1=CC([N+]([O-])=O)=CC=C1O VLZVIIYRNMWPSN-UHFFFAOYSA-N 0.000 description 3
- BDGHGQICSWOMQQ-UHFFFAOYSA-N 2-phenyl-1-benzofuran-5-amine Chemical compound C=1C2=CC(N)=CC=C2OC=1C1=CC=CC=C1 BDGHGQICSWOMQQ-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- NNVKLDYMPJGJMB-UHFFFAOYSA-N 5-bromo-2-(4-methylphenyl)-1,3-benzoxazole Chemical compound C1=CC(C)=CC=C1C1=NC2=CC(Br)=CC=C2O1 NNVKLDYMPJGJMB-UHFFFAOYSA-N 0.000 description 3
- FQOGSTGLRLMQOV-UHFFFAOYSA-N 5-nitro-3h-1,3-benzoxazole-2-thione Chemical compound [O-][N+](=O)C1=CC=C2OC(=S)NC2=C1 FQOGSTGLRLMQOV-UHFFFAOYSA-N 0.000 description 3
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 3
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 3
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
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- 125000006239 protecting group Chemical group 0.000 description 3
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- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
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- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 3
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- IWHJJSRRFYXEIS-UHFFFAOYSA-N n-benzyl-2-(4-chlorophenyl)-1,3-benzoxazol-5-amine Chemical compound C1=CC(Cl)=CC=C1C1=NC2=CC(NCC=3C=CC=CC=3)=CC=C2O1 IWHJJSRRFYXEIS-UHFFFAOYSA-N 0.000 description 1
- SWQSWTBOZUEKEI-UHFFFAOYSA-N n-butyl-2-(4-chlorophenyl)-1,3-benzoxazol-5-amine Chemical compound N=1C2=CC(NCCCC)=CC=C2OC=1C1=CC=C(Cl)C=C1 SWQSWTBOZUEKEI-UHFFFAOYSA-N 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
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- ANIYUUQAYWJIGF-UHFFFAOYSA-N phenoxy(phenyl)borinic acid Chemical compound C=1C=CC=CC=1B(O)OC1=CC=CC=C1 ANIYUUQAYWJIGF-UHFFFAOYSA-N 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- BXBUVIPNRGDTNE-UHFFFAOYSA-N sodium;hydrobromide Chemical compound [Na].Br BXBUVIPNRGDTNE-UHFFFAOYSA-N 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 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
- 230000009261 transgenic effect Effects 0.000 description 1
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- UKTDFYOZPFNQOQ-UHFFFAOYSA-N tributyl(thiophen-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CS1 UKTDFYOZPFNQOQ-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
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- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- Health & Medical Sciences (AREA)
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Furan Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (9)
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| GB0602768A GB0602768D0 (en) | 2006-02-10 | 2006-02-10 | Treatment of muscular dystrophy |
| GB0602768.4 | 2006-02-10 | ||
| GB0614690.6 | 2006-07-24 | ||
| GB0614690A GB0614690D0 (en) | 2006-07-24 | 2006-07-24 | Method of treatment of duchenne muscular dystrophy |
| GB0619281.9 | 2006-09-29 | ||
| GB0619281A GB0619281D0 (en) | 2006-09-29 | 2006-09-29 | Treatment of duchenne muscular dystrophy |
| GB0623983.4 | 2006-11-30 | ||
| GB0623983A GB0623983D0 (en) | 2006-11-30 | 2006-11-30 | Treatment of duchenne muscular dystrophy |
| PCT/GB2007/050055 WO2007091106A2 (en) | 2006-02-10 | 2007-02-09 | Treatment of duchenne muscular dystrophy |
Publications (1)
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-
2007
- 2007-02-09 DK DK07705368.4T patent/DK1986633T3/da active
- 2007-02-09 ES ES07705368.4T patent/ES2522290T3/es active Active
- 2007-02-09 SI SI200731544T patent/SI1986633T1/sl unknown
- 2007-02-09 BR BRPI0707719-0A patent/BRPI0707719A2/pt not_active Application Discontinuation
- 2007-02-09 PT PT77053684T patent/PT1986633E/pt unknown
- 2007-02-09 JP JP2008553834A patent/JP5376956B2/ja not_active Expired - Fee Related
- 2007-02-09 AU AU2007213451A patent/AU2007213451B2/en not_active Ceased
- 2007-02-09 KR KR1020087022077A patent/KR101426093B1/ko not_active Expired - Fee Related
- 2007-02-09 US US12/278,769 patent/US8518980B2/en not_active Expired - Fee Related
- 2007-02-09 PL PL07705368T patent/PL1986633T3/pl unknown
- 2007-02-09 MX MX2008010187A patent/MX2008010187A/es active IP Right Grant
- 2007-02-09 NZ NZ570625A patent/NZ570625A/en not_active IP Right Cessation
- 2007-02-09 WO PCT/GB2007/050055 patent/WO2007091106A2/en not_active Ceased
- 2007-02-09 CA CA2641880A patent/CA2641880C/en not_active Expired - Fee Related
- 2007-02-09 EP EP07705368.4A patent/EP1986633B1/en active Active
- 2007-02-09 KR KR1020137027768A patent/KR101472248B1/ko not_active Expired - Fee Related
-
2008
- 2008-08-07 IL IL193315A patent/IL193315A/en not_active IP Right Cessation
-
2013
- 2013-07-11 US US13/939,771 patent/US20140018320A1/en not_active Abandoned
- 2013-09-29 IL IL228598A patent/IL228598A0/en unknown
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- 2014-10-30 CY CY20141100891T patent/CY1115657T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK1986633T3 (da) | 2014-11-03 |
| KR20090010025A (ko) | 2009-01-28 |
| CA2641880C (en) | 2014-09-09 |
| AU2007213451B2 (en) | 2013-02-07 |
| IL193315A0 (en) | 2009-09-22 |
| US8518980B2 (en) | 2013-08-27 |
| EP1986633B1 (en) | 2014-07-30 |
| WO2007091106A2 (en) | 2007-08-16 |
| ES2522290T3 (es) | 2014-11-14 |
| EP1986633A2 (en) | 2008-11-05 |
| NZ570625A (en) | 2011-10-28 |
| CA2641880A1 (en) | 2007-08-16 |
| WO2007091106A3 (en) | 2008-03-06 |
| JP2009526034A (ja) | 2009-07-16 |
| CY1115657T1 (el) | 2017-01-25 |
| AU2007213451A1 (en) | 2007-08-16 |
| KR20130129476A (ko) | 2013-11-28 |
| MX2008010187A (es) | 2008-10-31 |
| US20090075938A1 (en) | 2009-03-19 |
| IL193315A (en) | 2016-02-29 |
| KR101472248B1 (ko) | 2014-12-16 |
| PT1986633E (pt) | 2014-11-05 |
| SI1986633T1 (sl) | 2015-03-31 |
| JP5376956B2 (ja) | 2013-12-25 |
| US20140018320A1 (en) | 2014-01-16 |
| KR101426093B1 (ko) | 2014-08-01 |
| PL1986633T3 (pl) | 2015-01-30 |
| HK1125577A1 (en) | 2009-08-14 |
| IL228598A0 (en) | 2013-12-31 |
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