CA2707521A1 - Imidazopyrazine compounds - Google Patents
Imidazopyrazine compounds Download PDFInfo
- Publication number
- CA2707521A1 CA2707521A1 CA2707521A CA2707521A CA2707521A1 CA 2707521 A1 CA2707521 A1 CA 2707521A1 CA 2707521 A CA2707521 A CA 2707521A CA 2707521 A CA2707521 A CA 2707521A CA 2707521 A1 CA2707521 A1 CA 2707521A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- substituted
- alkoxy
- compound according
- halo
- 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.)
- Abandoned
Links
- 150000005235 imidazopyrazines Chemical class 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 326
- 238000011282 treatment Methods 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 208000036142 Viral infection Diseases 0.000 claims abstract description 25
- 230000009385 viral infection Effects 0.000 claims abstract description 25
- 230000002265 prevention Effects 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 187
- 125000005843 halogen group Chemical group 0.000 claims description 123
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 115
- 125000003118 aryl group Chemical group 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 51
- 229910052736 halogen Inorganic materials 0.000 claims description 50
- 150000002367 halogens Chemical group 0.000 claims description 50
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 42
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 26
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 17
- 229940002612 prodrug Drugs 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 241000709664 Picornaviridae Species 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 230000000155 isotopic effect Effects 0.000 claims description 8
- 241000710831 Flavivirus Species 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
- 125000000753 cycloalkyl group Chemical group 0.000 description 66
- -1 imidazopyrazine compound Chemical class 0.000 description 64
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 55
- 239000007787 solid Substances 0.000 description 55
- 239000000203 mixture Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 49
- 241000711549 Hepacivirus C Species 0.000 description 48
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 39
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 37
- 150000003254 radicals Chemical class 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 125000003710 aryl alkyl group Chemical group 0.000 description 31
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 27
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 27
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 24
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 23
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- 201000010099 disease Diseases 0.000 description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000007429 general method Methods 0.000 description 15
- 125000004475 heteroaralkyl group Chemical group 0.000 description 15
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 125000005842 heteroatom Chemical group 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000013543 active substance Substances 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 125000004093 cyano group Chemical group *C#N 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 8
- 241000430519 Human rhinovirus sp. Species 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 230000010076 replication Effects 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 8
- 241000709661 Enterovirus Species 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 6
- 125000004442 acylamino group Chemical group 0.000 description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 229940090438 infergen Drugs 0.000 description 6
- 108010010648 interferon alfacon-1 Proteins 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- SIACJRVYIPXFKS-UHFFFAOYSA-N (4-sulfamoylphenyl)methylazanium;chloride Chemical compound Cl.NCC1=CC=C(S(N)(=O)=O)C=C1 SIACJRVYIPXFKS-UHFFFAOYSA-N 0.000 description 5
- MCEGPQSPRNOFMG-UHFFFAOYSA-N 3-bromo-8-chloroimidazo[1,2-a]pyrazine Chemical compound ClC1=NC=CN2C(Br)=CN=C12 MCEGPQSPRNOFMG-UHFFFAOYSA-N 0.000 description 5
- BICZJRAGTCRORZ-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(O)C=C1 BICZJRAGTCRORZ-UHFFFAOYSA-N 0.000 description 5
- XKRIRLKSWNHAHS-UHFFFAOYSA-N 6-methyl-7h-imidazo[1,2-a]pyrazin-8-one Chemical compound O=C1NC(C)=CN2C=CN=C21 XKRIRLKSWNHAHS-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 241000991587 Enterovirus C Species 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 125000001769 aryl amino group Chemical group 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 241001493065 dsRNA viruses Species 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- DVDRPJVFELVYQU-UHFFFAOYSA-N 1,6-dimethyl-7h-imidazo[1,2-a]pyrazin-1-ium-8-one;bromide Chemical compound [Br-].O=C1NC(C)=CN2C=C[N+](C)=C21 DVDRPJVFELVYQU-UHFFFAOYSA-N 0.000 description 4
- UIKPUVLIJJJXNA-UHFFFAOYSA-N 1-methylimidazole-2-carboxamide Chemical compound CN1C=CN=C1C(N)=O UIKPUVLIJJJXNA-UHFFFAOYSA-N 0.000 description 4
- KOYWJTGSMJPNFV-UHFFFAOYSA-N 3,6,8-tribromoimidazo[1,2-a]pyrazine Chemical compound BrC1=NC(Br)=CN2C(Br)=CN=C21 KOYWJTGSMJPNFV-UHFFFAOYSA-N 0.000 description 4
- HUWMOIPXXKXNBB-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-methylsulfanylimidazo[1,2-a]pyrazine Chemical compound C1=CC(OC)=CC=C1C1=CN=C2N1C=CN=C2SC HUWMOIPXXKXNBB-UHFFFAOYSA-N 0.000 description 4
- XHPDEMUFMYMMKA-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-methylsulfonylimidazo[1,2-a]pyrazine Chemical compound C1=CC(OC)=CC=C1C1=CN=C2N1C=CN=C2S(C)(=O)=O XHPDEMUFMYMMKA-UHFFFAOYSA-N 0.000 description 4
- MUOSLGHOTRMARQ-UHFFFAOYSA-N 3-[[[3-(4-methoxyphenyl)imidazo[1,2-a]pyrazin-8-yl]amino]methyl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=CN=C2N1C=CN=C2NCC1=CC=CC(S(N)(=O)=O)=C1 MUOSLGHOTRMARQ-UHFFFAOYSA-N 0.000 description 4
- HEOLCUBUYOTJDB-UHFFFAOYSA-N 3-amino-5-methyl-1h-pyrazin-2-one Chemical compound CC1=CN=C(O)C(N)=N1 HEOLCUBUYOTJDB-UHFFFAOYSA-N 0.000 description 4
- NRKMUXRBIBCNJJ-UHFFFAOYSA-N 3-bromo-8-chloro-2-methylimidazo[1,2-a]pyrazine Chemical compound ClC1=NC=CN2C(Br)=C(C)N=C21 NRKMUXRBIBCNJJ-UHFFFAOYSA-N 0.000 description 4
- PXLOJAAWXPGPBE-UHFFFAOYSA-N 3-bromo-8-chloro-5-methylimidazo[1,2-a]pyrazine Chemical compound CC1=CN=C(Cl)C2=NC=C(Br)N12 PXLOJAAWXPGPBE-UHFFFAOYSA-N 0.000 description 4
- SMVTUMRPQFJHLA-UHFFFAOYSA-N 3-bromo-8-chloro-6-methylimidazo[1,2-a]pyrazine Chemical compound ClC1=NC(C)=CN2C(Br)=CN=C21 SMVTUMRPQFJHLA-UHFFFAOYSA-N 0.000 description 4
- XBYIGALBZPSWNX-UHFFFAOYSA-N 3-bromo-8-methylsulfanylimidazo[1,2-a]pyrazine Chemical compound CSC1=NC=CN2C(Br)=CN=C12 XBYIGALBZPSWNX-UHFFFAOYSA-N 0.000 description 4
- MAQDQJWCSSCURR-UHFFFAOYSA-N 4-[5-(cyclopropanecarbonylamino)-2-(trifluoromethoxy)phenyl]-n-[4-[(4-propylsulfonylpiperazin-1-yl)methyl]phenyl]benzamide Chemical compound C1CN(S(=O)(=O)CCC)CCN1CC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2C(=CC=C(NC(=O)C3CC3)C=2)OC(F)(F)F)C=C1 MAQDQJWCSSCURR-UHFFFAOYSA-N 0.000 description 4
- CMWZIELOOYMVNV-UHFFFAOYSA-N 4-[[(3,6-dibromoimidazo[1,2-a]pyrazin-8-yl)amino]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC1=NC(Br)=CN2C1=NC=C2Br CMWZIELOOYMVNV-UHFFFAOYSA-N 0.000 description 4
- JPHRGNAQHVVFIP-UHFFFAOYSA-N 4-[[(3-bromo-2-methylimidazo[1,2-a]pyrazin-8-yl)amino]methyl]benzenesulfonamide Chemical compound N=1C=CN2C(Br)=C(C)N=C2C=1NCC1=CC=C(S(N)(=O)=O)C=C1 JPHRGNAQHVVFIP-UHFFFAOYSA-N 0.000 description 4
- GFQZMMGOKFRJEK-UHFFFAOYSA-N 4-[[(3-bromo-6-methylimidazo[1,2-a]pyrazin-8-yl)amino]methyl]benzenesulfonamide Chemical compound N=1C(C)=CN2C(Br)=CN=C2C=1NCC1=CC=C(S(N)(=O)=O)C=C1 GFQZMMGOKFRJEK-UHFFFAOYSA-N 0.000 description 4
- OMIXDFYSOQKFNX-UHFFFAOYSA-N 4-[[(3-bromoimidazo[1,2-a]pyrazin-8-yl)amino]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC1=NC=CN2C1=NC=C2Br OMIXDFYSOQKFNX-UHFFFAOYSA-N 0.000 description 4
- JVMWXARNXCVSIK-UHFFFAOYSA-N 4-[[[3-(2-fluoro-4-hydroxyphenyl)imidazo[1,2-a]pyrazin-8-yl]amino]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC1=NC=CN2C1=NC=C2C1=CC=C(O)C=C1F JVMWXARNXCVSIK-UHFFFAOYSA-N 0.000 description 4
- CEBHTJYMXSPAKL-UHFFFAOYSA-N 4-[[[3-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-8-yl]amino]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC1=NC=CN2C1=NC=C2C1=CC=C(O)C=C1 CEBHTJYMXSPAKL-UHFFFAOYSA-N 0.000 description 4
- WUPAWCXFTGKASP-UHFFFAOYSA-N 5-methyl-2-oxo-1h-pyrazine-3-carboxamide Chemical compound CC1=CN=C(O)C(C(N)=O)=N1 WUPAWCXFTGKASP-UHFFFAOYSA-N 0.000 description 4
- ZZPUXAQVYFAAMQ-UHFFFAOYSA-N 8-chloro-2-methylimidazo[1,2-a]pyrazine Chemical compound C1=CN=C(Cl)C2=NC(C)=CN21 ZZPUXAQVYFAAMQ-UHFFFAOYSA-N 0.000 description 4
- BUMYUJNTASOXCN-UHFFFAOYSA-N 8-chloro-5-methylimidazo[1,2-a]pyrazine Chemical compound CC1=CN=C(Cl)C2=NC=CN12 BUMYUJNTASOXCN-UHFFFAOYSA-N 0.000 description 4
- FXONOQAQNTUFFX-UHFFFAOYSA-N 8-chloro-6-methylimidazo[1,2-a]pyrazine Chemical compound ClC1=NC(C)=CN2C=CN=C21 FXONOQAQNTUFFX-UHFFFAOYSA-N 0.000 description 4
- PREWHWRWNMLCNH-UHFFFAOYSA-N 8-chloroimidazo[1,2-a]pyrazine Chemical compound ClC1=NC=CN2C=CN=C12 PREWHWRWNMLCNH-UHFFFAOYSA-N 0.000 description 4
- 101001023866 Arabidopsis thaliana Mannosyl-oligosaccharide glucosidase GCS1 Proteins 0.000 description 4
- 241000709687 Coxsackievirus Species 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical group 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 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
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0716292.8A GB0716292D0 (en) | 2007-08-21 | 2007-08-21 | Imidazopyrazine compounds |
| GB0716292.8 | 2007-08-21 | ||
| PCT/EP2008/060896 WO2009024585A2 (en) | 2007-08-21 | 2008-08-20 | Imidazo [1,2-a] pyrazine compounds for treatment of viral infections such as hepatitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2707521A1 true CA2707521A1 (en) | 2009-02-26 |
Family
ID=38566736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2707521A Abandoned CA2707521A1 (en) | 2007-08-21 | 2008-08-20 | Imidazopyrazine compounds |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US8362018B2 (enExample) |
| EP (2) | EP2567960A3 (enExample) |
| JP (1) | JP2010536825A (enExample) |
| KR (1) | KR20100081294A (enExample) |
| CN (1) | CN101835780B (enExample) |
| AU (1) | AU2008290531A1 (enExample) |
| BR (1) | BRPI0815717A2 (enExample) |
| CA (1) | CA2707521A1 (enExample) |
| CY (1) | CY1113872T1 (enExample) |
| DK (1) | DK2193131T3 (enExample) |
| ES (1) | ES2404415T3 (enExample) |
| GB (1) | GB0716292D0 (enExample) |
| HR (1) | HRP20130202T1 (enExample) |
| MX (1) | MX2010001733A (enExample) |
| NZ (1) | NZ584108A (enExample) |
| PL (1) | PL2193131T3 (enExample) |
| PT (1) | PT2193131E (enExample) |
| SI (1) | SI2193131T1 (enExample) |
| WO (1) | WO2009024585A2 (enExample) |
| ZA (1) | ZA201002009B (enExample) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0716292D0 (en) * | 2007-08-21 | 2007-09-26 | Biofocus Dpi Ltd | Imidazopyrazine compounds |
| JP5216912B2 (ja) | 2008-04-29 | 2013-06-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体拮抗薬としてのインダゾール化合物 |
| JP5411927B2 (ja) | 2008-05-06 | 2014-02-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１アンタゴニストとしてのピラゾール化合物 |
| PE20110854A1 (es) | 2008-09-26 | 2011-12-23 | Boehringer Ingelheim Int | DERIVADOS DE 1-FENIL-1H-PIRAZOLO[3,4-c]PIRIDINA-4-CARBONILAMINA COMO ANTAGONISTAS DE LOS RECEPTORES CCR1 |
| TW201107329A (en) | 2009-07-30 | 2011-03-01 | Oncotherapy Science Inc | Fused imidazole derivative having ttk inhibitory action |
| AP2012006204A0 (en) | 2009-10-21 | 2012-04-30 | Boehringer Ingelheim Int | Indazole and pyrazolopyridine compounds as CCR1 receptor antagonists. |
| JP5542214B2 (ja) | 2009-10-27 | 2014-07-09 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体アンタゴニストとしての複素環化合物 |
| PH12012500778A1 (en) | 2009-10-30 | 2012-11-26 | Janssen Pharmaceutica Nv | IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS |
| IN2012DN05081A (enExample) * | 2009-12-08 | 2015-10-09 | Boehringer Ingelheim Int | |
| AR080754A1 (es) | 2010-03-09 | 2012-05-09 | Janssen Pharmaceutica Nv | Derivados de imidazo (1,2-a) pirazina y su uso como inhibidores de pde10 |
| ES2551407T3 (es) * | 2010-03-18 | 2015-11-18 | Bayer Intellectual Property Gmbh | Imidazopirazinas |
| US8871786B2 (en) | 2010-04-30 | 2014-10-28 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as CCR1 receptor antagonists |
| CN103038235B (zh) | 2010-06-01 | 2015-07-29 | 拜耳知识产权有限责任公司 | 取代的咪唑并吡嗪 |
| CA2821829A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Intellectual Property Gmbh | Imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| US20140135319A1 (en) | 2010-12-17 | 2014-05-15 | Bayer Intellectual Property Gmbh | 6-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| WO2012080228A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | 6-thio-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| WO2012080232A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | 2-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| US9284317B2 (en) * | 2010-12-17 | 2016-03-15 | Bayer Intellectual Property Gmbh | Substituted imidazo[1,2-a]pyrazines as MPS-1 inhibitors |
| US20140187548A1 (en) | 2010-12-17 | 2014-07-03 | Bayer Intellectual Property Gmbh | 6 substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| US8546442B2 (en) | 2010-12-23 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Pyrazolopiperidine compounds as CCR1 receptor antagonists |
| GB201109763D0 (en) * | 2011-06-10 | 2011-07-27 | Ucl Business Plc | Compounds |
| JP6115962B2 (ja) | 2011-06-27 | 2017-04-19 | ヤンセン ファーマシューティカ エヌ．ベー． | １−アリール−４−メチル−［１，２，４］トリアゾロ［４，３−ａ］キノキサリン誘導体 |
| JPWO2013061962A1 (ja) * | 2011-10-24 | 2015-04-02 | 武田薬品工業株式会社 | 二環性化合物 |
| WO2014001314A1 (en) | 2012-06-26 | 2014-01-03 | Janssen Pharmaceutica Nv | Combinations comprising pde 2 inhibitors such as 1-aryl-4-methyl- [1,2,4] triazolo [4,3-a] quinoxaline compounds and pde 10 inhibitors for use in the treatment of neurological or metabolic disorders |
| AU2013289284B2 (en) | 2012-07-09 | 2017-03-30 | Janssen Pharmaceutica Nv | Inhibitors of phosphodiesterase 10 enzyme |
| WO2016130501A1 (en) | 2015-02-09 | 2016-08-18 | Incyte Corporation | Aza-heteroaryl compounds as pi3k-gamma inhibitors |
| BR112017023038A2 (pt) * | 2015-04-29 | 2018-07-03 | Janssen Pharmaceutica Nv | imidazopirazinas e pirazolopirimidinas e seu uso como moduladores do receptor ampa |
| BR122023023802A2 (pt) | 2015-04-29 | 2023-12-26 | Janssen Pharmaceutica Nv | Compostos azabenzimidazóis, seu uso como moduladores do receptor de ampa e composições farmacêuticas que os compreendem |
| CN107949563B (zh) * | 2015-06-24 | 2020-06-05 | 库洛维公司 | 治疗中有用的吡唑并[1,5-a]三嗪-4-胺衍生物 |
| JP6507976B2 (ja) * | 2015-09-30 | 2019-05-08 | 東レ株式会社 | イミダゾール−２−カルボン酸エステル誘導体又はその塩の製造方法 |
| RS63359B1 (sr) | 2015-11-06 | 2022-07-29 | Incyte Corp | Heterociklična jedinjenja kao inhibitori pi3k-gama |
| ES2995198T3 (en) | 2016-01-05 | 2025-02-07 | Incyte Corp | Pyridine compounds as pi3k-gamma inhibitors |
| HK1250945A1 (zh) * | 2016-03-31 | 2019-01-18 | 罗马克实验室有限公司 | 用於治疗病毒性感染的噻唑化物化合物 |
| TW201803871A (zh) | 2016-06-24 | 2018-02-01 | 英塞特公司 | 作為ＰＩ３Ｋ-γ抑制劑之雜環化合物 |
| UY37381A (es) | 2016-08-30 | 2018-03-23 | Glaxosmithkline Ip No 2 Ltd | Compuestos que inhiben proteasas 3c y 3cl y métodos de uso de los mismos |
| KR102717072B1 (ko) | 2017-10-18 | 2024-10-15 | 인사이트 코포레이션 | Pi3k-감마 저해제로서의 3차 하이드록시기로 치환된 축합된 이미다졸 유도체 |
| JP7133023B2 (ja) | 2018-01-17 | 2022-09-07 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | Ｐｉ４ｋｉｉｉベータ阻害剤 |
| TWI811428B (zh) | 2018-08-21 | 2023-08-11 | 日商杏林製藥股份有限公司 | 雙環雜芳香環衍生物 |
| CR20250050A (es) | 2018-09-05 | 2025-03-19 | Incyte Corp | Formas cristalinas de un inhibidor de fosfoinositida 3–quinasa (pi3k) (divisional 2021-0165) |
| CN109369545B (zh) * | 2018-12-14 | 2020-04-10 | 东营曜康医药科技有限公司 | 2-甲基-5-甲酸吡嗪的合成工艺 |
| US20230014730A1 (en) | 2019-09-23 | 2023-01-19 | Nanjing Zhengxiang Pharmaceuticals Co., Ltd. | Phosphodiesterase inhibitors and use |
| WO2021061803A1 (en) | 2019-09-23 | 2021-04-01 | Nanjing Zhengxiang Pharmaceuticals Co., Ltd. | Phosphodiesterase inhibitors and use |
| CN115667266A (zh) | 2020-06-01 | 2023-01-31 | 豪夫迈·罗氏有限公司 | 新型咪唑并吡嗪衍生物 |
| EP4161930A1 (en) * | 2020-06-08 | 2023-04-12 | F. Hoffmann-La Roche AG | Novel imidazo-pyrazine derivatives |
| CN113929633A (zh) * | 2021-10-27 | 2022-01-14 | 山东大学 | 一种法匹拉韦的合成方法及其应用 |
| CN113831255B (zh) * | 2021-11-25 | 2022-03-11 | 山东诚创蓝海医药科技有限公司 | 一种2-氨基丙二酰胺的制备方法 |
| CN115489188B (zh) * | 2022-10-09 | 2023-08-29 | 安徽国风新材料股份有限公司 | 一种家居保护用聚酯薄膜及其制备方法 |
| EP4623911A1 (en) | 2024-03-25 | 2025-10-01 | ETH Zurich | Pi4kb inhibitors for the treatment of fatty liver disease |
| EP4623912A1 (en) | 2024-03-25 | 2025-10-01 | ETH Zurich | A method for defattening a steatotic liver ex vivo |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2607813B1 (fr) * | 1986-12-05 | 1989-03-31 | Montpellier I Universite | Alkylamino-8 imidazo (1,2-a) pyrazines et derives, leur preparation et leur application en therapeutique |
| DE19915178A1 (de) | 1999-04-03 | 2000-10-05 | Univ Mainz Johannes Gutenberg | Hepatitis C Virus Zellkultursystem |
| DK1296998T3 (da) | 2000-05-23 | 2011-12-12 | Univ Washington | HCV-varianter |
| AU2002225895A1 (en) | 2000-11-07 | 2002-05-21 | Anadys Pharmaceuticals, Inc. | Hepatitis c virus constructs characterized by high efficiency replication |
| ES2287074T3 (es) | 2000-12-22 | 2007-12-16 | Boehringer Ingelheim (Canada) Ltd. | Molecula de rna autorreplicante del virus de la hepatitis c. |
| EP2050822B1 (en) | 2001-01-23 | 2013-07-31 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Hepatitis C virus replicons and replicon enhanced cells |
| WO2002060492A1 (en) * | 2001-01-30 | 2002-08-08 | Cytopia Pty Ltd | Methods of inhibiting kinases |
| JP4799864B2 (ja) | 2002-09-23 | 2011-10-26 | シェーリング コーポレイション | サイクリン依存性キナーゼインヒビターとしてのイミダゾピラジン |
| AU2007200401A1 (en) * | 2002-09-23 | 2007-02-22 | Schering Corporation | Imidazopyrazines as cyclin dependent kinase inhibitors |
| US7576085B2 (en) * | 2002-09-23 | 2009-08-18 | Schering Corporation | Imidazopyrazines as cyclin dependent kinase inhibitors |
| DE602004024658D1 (de) | 2003-02-13 | 2010-01-28 | Merck & Co Inc | Verfahren zur vermittlung von zellkulturreplikationsaktivität an unterschiedliche hepatitis-c-virus-isolate |
| AR043002A1 (es) | 2003-02-18 | 2005-07-13 | Altana Pharma Ag | Imidazopirazinas 6-substituidos |
| US7186832B2 (en) | 2003-02-20 | 2007-03-06 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7157460B2 (en) * | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| EP1945216A1 (en) | 2005-11-10 | 2008-07-23 | Schering Corporation | Methods for inhibiting protein kinases |
| EP1945644A2 (en) | 2005-11-10 | 2008-07-23 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| WO2008030795A2 (en) | 2006-09-05 | 2008-03-13 | Boards Of Regents, The University Of Texas System | Compositions and methods for inhibition of tyrosine kinases |
| US8268809B2 (en) * | 2006-09-05 | 2012-09-18 | Emory University | Kinase inhibitors for preventing or treating pathogen infection and method of use thereof |
| PE20080931A1 (es) | 2006-11-08 | 2008-07-19 | Schering Corp | Imidazopirazinas como inhibidores de proteina quinasa |
| WO2008059373A1 (en) | 2006-11-17 | 2008-05-22 | Raqualia Pharma Inc. | Imidazo [1, 2-a] pyrazine derivatives and their use as acid pump antagonists |
| US8243049B2 (en) | 2006-12-20 | 2012-08-14 | 3M Innovative Properties Company | Untethered stylus employing low current power converter |
| GB0716292D0 (en) * | 2007-08-21 | 2007-09-26 | Biofocus Dpi Ltd | Imidazopyrazine compounds |
-
2007
- 2007-08-21 GB GBGB0716292.8A patent/GB0716292D0/en not_active Ceased
-
2008
- 2008-08-20 EP EP12188861.4A patent/EP2567960A3/en not_active Withdrawn
- 2008-08-20 KR KR1020107005549A patent/KR20100081294A/ko not_active Ceased
- 2008-08-20 EP EP08787346A patent/EP2193131B1/en not_active Not-in-force
- 2008-08-20 ES ES08787346T patent/ES2404415T3/es active Active
- 2008-08-20 PL PL08787346T patent/PL2193131T3/pl unknown
- 2008-08-20 DK DK08787346.9T patent/DK2193131T3/da active
- 2008-08-20 CA CA2707521A patent/CA2707521A1/en not_active Abandoned
- 2008-08-20 AU AU2008290531A patent/AU2008290531A1/en not_active Abandoned
- 2008-08-20 MX MX2010001733A patent/MX2010001733A/es active IP Right Grant
- 2008-08-20 WO PCT/EP2008/060896 patent/WO2009024585A2/en not_active Ceased
- 2008-08-20 HR HRP20130202AT patent/HRP20130202T1/hr unknown
- 2008-08-20 NZ NZ584108A patent/NZ584108A/en not_active IP Right Cessation
- 2008-08-20 CN CN2008801108961A patent/CN101835780B/zh not_active Expired - Fee Related
- 2008-08-20 US US12/674,525 patent/US8362018B2/en not_active Expired - Fee Related
- 2008-08-20 BR BRPI0815717-0A2A patent/BRPI0815717A2/pt not_active IP Right Cessation
- 2008-08-20 JP JP2010521417A patent/JP2010536825A/ja not_active Ceased
- 2008-08-20 PT PT87873469T patent/PT2193131E/pt unknown
- 2008-08-20 SI SI200830948T patent/SI2193131T1/sl unknown
-
2010
- 2010-03-19 ZA ZA2010/02009A patent/ZA201002009B/en unknown
-
2013
- 2013-04-03 CY CY20131100277T patent/CY1113872T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK2193131T3 (da) | 2013-04-22 |
| WO2009024585A2 (en) | 2009-02-26 |
| NZ584108A (en) | 2012-06-29 |
| EP2193131B1 (en) | 2013-01-30 |
| BRPI0815717A2 (pt) | 2015-02-10 |
| MX2010001733A (es) | 2010-07-06 |
| ES2404415T3 (es) | 2013-05-27 |
| EP2567960A3 (en) | 2013-06-05 |
| ZA201002009B (en) | 2010-12-29 |
| US8362018B2 (en) | 2013-01-29 |
| GB0716292D0 (en) | 2007-09-26 |
| HRP20130202T1 (hr) | 2013-04-30 |
| EP2193131A2 (en) | 2010-06-09 |
| HK1143810A1 (en) | 2011-01-14 |
| WO2009024585A3 (en) | 2009-08-06 |
| KR20100081294A (ko) | 2010-07-14 |
| PT2193131E (pt) | 2013-04-04 |
| US20110166147A1 (en) | 2011-07-07 |
| PL2193131T3 (pl) | 2013-07-31 |
| AU2008290531A1 (en) | 2009-02-26 |
| CN101835780A (zh) | 2010-09-15 |
| SI2193131T1 (sl) | 2013-06-28 |
| EP2567960A2 (en) | 2013-03-13 |
| JP2010536825A (ja) | 2010-12-02 |
| CY1113872T1 (el) | 2016-07-27 |
| CN101835780B (zh) | 2013-09-18 |
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