KR20140037195A - 신규 프탈라지논-피롤로피리미딘카복스아미드 유도체 - Google Patents
신규 프탈라지논-피롤로피리미딘카복스아미드 유도체 Download PDFInfo
- Publication number
- KR20140037195A KR20140037195A KR1020147000392A KR20147000392A KR20140037195A KR 20140037195 A KR20140037195 A KR 20140037195A KR 1020147000392 A KR1020147000392 A KR 1020147000392A KR 20147000392 A KR20147000392 A KR 20147000392A KR 20140037195 A KR20140037195 A KR 20140037195A
- Authority
- KR
- South Korea
- Prior art keywords
- oxo
- piperidin
- dimethoxyphenyl
- pyrrolo
- cyclopropylmethoxy
- 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.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 claims abstract description 574
- 239000000126 substance Substances 0.000 claims abstract description 5
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract 3
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract 3
- -1 -C (O) NH 2 Chemical group 0.000 claims description 454
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 284
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 265
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 125
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 239000001257 hydrogen Substances 0.000 claims description 91
- 150000003839 salts Chemical class 0.000 claims description 76
- 239000011737 fluorine Substances 0.000 claims description 71
- 229910052731 fluorine Inorganic materials 0.000 claims description 71
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 47
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 45
- 125000001153 fluoro group Chemical group F* 0.000 claims description 42
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 36
- 150000002431 hydrogen Chemical group 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical group 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 31
- 239000000460 chlorine Chemical group 0.000 claims description 27
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 23
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 22
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 22
- 125000003003 spiro group Chemical group 0.000 claims description 22
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 17
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 15
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 14
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 13
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 11
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 11
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 11
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 11
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 11
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 7
- NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical group [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims description 6
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 239000010977 jade Substances 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 4
- 230000001154 acute effect Effects 0.000 claims 4
- 230000001684 chronic effect Effects 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 4
- 208000023504 respiratory system disease Diseases 0.000 claims 4
- 206010006458 Bronchitis chronic Diseases 0.000 claims 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims 2
- 206010014561 Emphysema Diseases 0.000 claims 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 2
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 208000006673 asthma Diseases 0.000 claims 2
- 206010006451 bronchitis Diseases 0.000 claims 2
- 208000007451 chronic bronchitis Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000003119 guanylate cyclase activator Substances 0.000 claims 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 claims 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 claims 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 claims 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims 1
- 229930003316 Vitamin D Natural products 0.000 claims 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 claims 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 229940097320 beta blocking agent Drugs 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 239000000812 cholinergic antagonist Chemical class 0.000 claims 1
- 239000003246 corticosteroid Chemical class 0.000 claims 1
- 229960001334 corticosteroids Drugs 0.000 claims 1
- 229940082657 digitalis glycosides Drugs 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 229940030606 diuretics Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 1
- 229960003444 immunosuppressant agent Drugs 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
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- 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 claims 1
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- 229940066294 lung surfactant Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229960003073 pirfenidone Drugs 0.000 claims 1
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 claims 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 1
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- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical class N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 550
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 254
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 247
- 239000000203 mixture Substances 0.000 description 211
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- 239000010410 layer Substances 0.000 description 171
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 137
- 235000019439 ethyl acetate Nutrition 0.000 description 131
- 239000000741 silica gel Substances 0.000 description 130
- 229910002027 silica gel Inorganic materials 0.000 description 130
- 235000017557 sodium bicarbonate Nutrition 0.000 description 123
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 123
- 229920006395 saturated elastomer Polymers 0.000 description 121
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 116
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- GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 64
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- 239000003480 eluent Substances 0.000 description 54
- 238000004108 freeze drying Methods 0.000 description 54
- 239000000725 suspension Substances 0.000 description 49
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 48
- 238000002953 preparative HPLC Methods 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- GHJORKVUGKXEEY-UHFFFAOYSA-N 4-[5-(cyclopropylmethoxy)-1,3-benzodioxol-4-yl]-5h-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid Chemical compound N1=CN=C2C(C(=O)O)=CNC2=C1C1=C2OCOC2=CC=C1OCC1CC1 GHJORKVUGKXEEY-UHFFFAOYSA-N 0.000 description 40
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- 239000002904 solvent Substances 0.000 description 29
- 239000007821 HATU Substances 0.000 description 26
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- SIXISCAJFLMLLM-UHFFFAOYSA-N 5-(cyclopropylmethoxy)-1,3-benzodioxole Chemical compound C=1C=C2OCOC2=CC=1OCC1CC1 SIXISCAJFLMLLM-UHFFFAOYSA-N 0.000 description 23
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
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- 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 11
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910021135 KPF6 Inorganic materials 0.000 description 1
- RGHNJXZEOKUKBD-KLVWXMOXSA-N L-gluconic acid Chemical class OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-KLVWXMOXSA-N 0.000 description 1
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
- 125000002061 L-isoleucyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](C([H])([H])[H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- ZYKSLMIKRCOCDC-UHFFFAOYSA-N N1C(C(=O)N)=NC=C2N=CC=C21 Chemical class N1C(C(=O)N)=NC=C2N=CC=C21 ZYKSLMIKRCOCDC-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
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- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical class O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- PTJGRIAIIRSGSR-OYUWMTPXSA-N benzyl (4r)-5-[4-[(4as,8ar)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,6,7,8,8a-hexahydrophthalazin-2-yl]piperidin-1-yl]-4-amino-5-oxopentanoate Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CCCC[C@H]1C1=O)=NN1C1CCN(C(=O)[C@H](N)CCC(=O)OCC=2C=CC=CC=2)CC1 PTJGRIAIIRSGSR-OYUWMTPXSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- QFVRLYRYKCLRMD-UHFFFAOYSA-N cyclodecane-1,6-diol Chemical compound OC1CCCCC(O)CCCC1 QFVRLYRYKCLRMD-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 150000004721 gamma keto acids Chemical class 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940116871 l-lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 1
- WCCDMVZNXNVVQM-UHFFFAOYSA-N piperidin-4-ylhydrazine Chemical compound NNC1CCNCC1 WCCDMVZNXNVVQM-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003883 substance clean up Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11170440 | 2011-06-17 | ||
| EP11170440.9 | 2011-06-17 | ||
| PCT/EP2012/061084 WO2012171900A1 (en) | 2011-06-17 | 2012-06-12 | Novel phthalazinone-pyrrolopyrimidinecarboxamide derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140037195A true KR20140037195A (ko) | 2014-03-26 |
Family
ID=44764312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147000392A Withdrawn KR20140037195A (ko) | 2011-06-17 | 2012-06-12 | 신규 프탈라지논-피롤로피리미딘카복스아미드 유도체 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20140112945A1 (https=) |
| EP (1) | EP2721030B1 (https=) |
| JP (1) | JP5980318B2 (https=) |
| KR (1) | KR20140037195A (https=) |
| CN (1) | CN103582644B (https=) |
| AR (1) | AR086915A1 (https=) |
| AU (1) | AU2012269133A1 (https=) |
| BR (1) | BR112013031791A2 (https=) |
| CA (1) | CA2837248A1 (https=) |
| CL (1) | CL2013003556A1 (https=) |
| CO (1) | CO6852074A2 (https=) |
| CR (1) | CR20130656A (https=) |
| DO (1) | DOP2013000298A (https=) |
| EA (1) | EA023713B1 (https=) |
| EC (1) | ECSP13013076A (https=) |
| ES (1) | ES2564882T3 (https=) |
| MA (1) | MA35269B1 (https=) |
| MX (1) | MX2013014888A (https=) |
| PE (1) | PE20140648A1 (https=) |
| PH (1) | PH12013502546A1 (https=) |
| TN (1) | TN2013000439A1 (https=) |
| WO (1) | WO2012171900A1 (https=) |
Families Citing this family (5)
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| KR20170132880A (ko) | 2015-04-09 | 2017-12-04 | 갈데르마 소시에떼아노님 | 약학 조성물 및 이의 용도 |
| HRP20190088T1 (hr) | 2015-04-09 | 2019-03-22 | Galderma Sa | Ekstrakt iz prirodnog indiga i postupak njegove priprave |
| EP3280428A1 (en) | 2015-04-09 | 2018-02-14 | Galderma S.A. | Antibacterial indigo naturalis or indigo-producing plant extract and use thereof |
| EP3215169A1 (en) * | 2015-04-09 | 2017-09-13 | Galderma S.A. | Treatment of atopic dermatitis with indigo naturalis or indigo producing plant extract |
| US12383547B2 (en) | 2020-07-01 | 2025-08-12 | Vanderbilt University | Methods of treatment for a kidney disease |
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| GB8828477D0 (en) | 1988-12-06 | 1989-01-05 | Riker Laboratories Inc | Medical aerosol formulations |
| DE407028T1 (de) | 1989-05-31 | 1994-03-17 | Fisons Plc | Medikament und Inhalationsvorrichtung dafür. |
| GB8921222D0 (en) | 1989-09-20 | 1989-11-08 | Riker Laboratories Inc | Medicinal aerosol formulations |
| IL97065A (en) | 1990-02-02 | 1994-01-25 | Fisons Plc | Repellent preparations for aerosol |
| DE4003272A1 (de) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | Neue treibgasmischungen und ihre verwendung in arzneimittelzubereitungen |
| AU654813B2 (en) | 1990-03-23 | 1994-11-24 | Minnesota Mining And Manufacturing Company | The use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations |
| JP2769925B2 (ja) | 1990-10-18 | 1998-06-25 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | ベクロメタゾン１７，２１ジプロピオネートを含んで成るエアロゾル製剤 |
| AU650953B2 (en) | 1991-03-21 | 1994-07-07 | Novartis Ag | Inhaler |
| IL104068A (en) | 1991-12-12 | 1998-10-30 | Glaxo Group Ltd | Surfactant-free pharmaceutical aerosol formulation comprising 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n- propane as propellant |
| GB9213874D0 (en) | 1992-06-30 | 1992-08-12 | Fisons Plc | Process to novel medicament form |
| GB9306703D0 (en) | 1993-03-31 | 1993-05-26 | Fisons Plc | Inhalation device |
| IL111194A (en) | 1993-10-08 | 1998-02-08 | Fisons Plc | Process for the production of medicament formulations |
| TR199901653T2 (xx) * | 1997-01-15 | 1999-10-21 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Fitalazinonlar. |
| JP2002506856A (ja) * | 1998-03-14 | 2002-03-05 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | フタラジノンｐｄｅｉｉｉ／ｉｖ阻害剤 |
| CN1150890C (zh) | 1998-08-04 | 2004-05-26 | 杰格研究股份公司 | 药用气溶胶制剂 |
| US6397838B1 (en) | 1998-12-23 | 2002-06-04 | Battelle Pulmonary Therapeutics, Inc. | Pulmonary aerosol delivery device and method |
| JP4677102B2 (ja) | 1999-04-23 | 2011-04-27 | バテル・メモリアル・インスティテュート | エーロゾル給送装置及びエーロゾル小滴を給送する方法 |
| AU777169B2 (en) | 1999-04-23 | 2004-10-07 | Battelle Memorial Institute | High mass transfer electrosprayer |
| NZ522882A (en) * | 2000-06-05 | 2004-07-30 | Altana Pharma Bv | Pyridazinone compounds effective as beta-2-adrenoreceptor agonists as well as PDE4-inhibitors |
| CA2425035A1 (en) | 2000-10-09 | 2002-04-18 | 3M Innovative Properties Company | Medicinal aerosol formulations |
| EE05386B1 (et) | 2001-02-15 | 2011-02-15 | ALTANA�Pharma�AG | Ftalasinoon-piperidinoderivaadid,ÁnendeÁkasutamineÁjaÁravim |
| NZ529221A (en) | 2001-04-25 | 2005-04-29 | Altana Pharma Ag | Phthalazinones with PDE-inhibiting properties for treatment of airway disorders and other inflammatory conditions |
| AU2003255376A1 (en) | 2002-08-10 | 2004-03-11 | Altana Pharma Ag | Piperidine-derivatives as pde4 inhibitors |
| CA2494613C (en) | 2002-08-10 | 2011-06-28 | Altana Pharma Ag | Pyrrolidinedione substituted piperidine-phthalazones as pde4 inhibitors |
| WO2004018451A1 (en) | 2002-08-10 | 2004-03-04 | Altana Pharma Ag | Pyridazinone-derivatives as pde4 inhibitors |
| WO2004062671A2 (en) * | 2003-01-14 | 2004-07-29 | Altana Pharma Ag | Pde4 inhibitors for the treatment of neoplasms of lymphoid cells |
| WO2005075457A1 (en) | 2004-02-04 | 2005-08-18 | Altana Pharma Ag | Phthalazinone-derivatives as pde4 inhibitors |
| EP1716133B1 (en) | 2004-02-04 | 2008-03-26 | Nycomed GmbH | 2-(piperidin-4-yl)-4,5-dihydro-2h-pyridazin-3-one derivatives as pde4 inhibitors |
| AR070454A1 (es) * | 2008-02-27 | 2010-04-07 | Nycomed Gmbh | Pirrolopirimidincarboxamidas y composiciones farmaceuticas que las comprenden |
| AR077898A1 (es) * | 2009-08-26 | 2011-09-28 | Nycomed Gmbh | Metilpirrolopirimidincarboxamidas |
-
2012
- 2012-06-12 AU AU2012269133A patent/AU2012269133A1/en not_active Abandoned
- 2012-06-12 ES ES12728453.7T patent/ES2564882T3/es active Active
- 2012-06-12 MX MX2013014888A patent/MX2013014888A/es not_active Application Discontinuation
- 2012-06-12 JP JP2014515155A patent/JP5980318B2/ja not_active Expired - Fee Related
- 2012-06-12 WO PCT/EP2012/061084 patent/WO2012171900A1/en not_active Ceased
- 2012-06-12 BR BR112013031791A patent/BR112013031791A2/pt not_active IP Right Cessation
- 2012-06-12 EA EA201400001A patent/EA023713B1/ru not_active IP Right Cessation
- 2012-06-12 CN CN201280028413.XA patent/CN103582644B/zh not_active Expired - Fee Related
- 2012-06-12 EP EP12728453.7A patent/EP2721030B1/en active Active
- 2012-06-12 KR KR1020147000392A patent/KR20140037195A/ko not_active Withdrawn
- 2012-06-12 US US14/125,187 patent/US20140112945A1/en not_active Abandoned
- 2012-06-12 CA CA2837248A patent/CA2837248A1/en not_active Abandoned
- 2012-06-12 PH PH1/2013/502546A patent/PH12013502546A1/en unknown
- 2012-06-12 PE PE2013002801A patent/PE20140648A1/es not_active Application Discontinuation
- 2012-06-12 AR ARP120102088A patent/AR086915A1/es unknown
-
2013
- 2013-10-29 TN TNP2013000439A patent/TN2013000439A1/fr unknown
- 2013-12-11 EC ECSP13013076 patent/ECSP13013076A/es unknown
- 2013-12-11 CL CL2013003556A patent/CL2013003556A1/es unknown
- 2013-12-11 DO DO2013000298A patent/DOP2013000298A/es unknown
- 2013-12-13 CR CR20130656A patent/CR20130656A/es unknown
-
2014
- 2014-01-10 CO CO14004200A patent/CO6852074A2/es not_active Application Discontinuation
- 2014-01-16 MA MA36689A patent/MA35269B1/fr unknown
-
2015
- 2015-12-03 US US14/958,141 patent/US20160108049A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2837248A1 (en) | 2012-12-20 |
| JP2014517021A (ja) | 2014-07-17 |
| US20160108049A1 (en) | 2016-04-21 |
| ES2564882T3 (es) | 2016-03-29 |
| WO2012171900A1 (en) | 2012-12-20 |
| EA023713B1 (ru) | 2016-07-29 |
| AU2012269133A1 (en) | 2014-01-30 |
| BR112013031791A2 (pt) | 2017-01-31 |
| EP2721030B1 (en) | 2015-12-16 |
| ECSP13013076A (es) | 2014-01-31 |
| MA35269B1 (fr) | 2014-07-03 |
| EA201400001A1 (ru) | 2014-05-30 |
| CN103582644A (zh) | 2014-02-12 |
| EP2721030A1 (en) | 2014-04-23 |
| JP5980318B2 (ja) | 2016-08-31 |
| DOP2013000298A (es) | 2014-03-31 |
| MX2013014888A (es) | 2014-02-27 |
| PH12013502546A1 (en) | 2014-01-27 |
| CL2013003556A1 (es) | 2014-06-13 |
| CN103582644B (zh) | 2016-07-20 |
| TN2013000439A1 (en) | 2015-03-30 |
| PE20140648A1 (es) | 2014-05-30 |
| US20140112945A1 (en) | 2014-04-24 |
| CR20130656A (es) | 2014-02-18 |
| AR086915A1 (es) | 2014-01-29 |
| CO6852074A2 (es) | 2014-01-30 |
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