CA2614232A1 - Pyrazolo [3,4-d] azepine derivatives as histamine h3 antagonists - Google Patents
Pyrazolo [3,4-d] azepine derivatives as histamine h3 antagonists Download PDFInfo
- Publication number
- CA2614232A1 CA2614232A1 CA002614232A CA2614232A CA2614232A1 CA 2614232 A1 CA2614232 A1 CA 2614232A1 CA 002614232 A CA002614232 A CA 002614232A CA 2614232 A CA2614232 A CA 2614232A CA 2614232 A1 CA2614232 A1 CA 2614232A1
- Authority
- CA
- Canada
- Prior art keywords
- methanol
- mixture
- aryl
- heteroaryl
- alkyl
- 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
- 239000003395 histamine H3 receptor antagonist Substances 0.000 title description 2
- RMUDBHOUKWNOLH-UHFFFAOYSA-N pyrazolo[3,4-d]azepine Chemical class C1=CN=CC=C2C=NN=C21 RMUDBHOUKWNOLH-UHFFFAOYSA-N 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 102
- 230000008569 process Effects 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 9
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 210
- -1 hydroxy, cyano, amino Chemical group 0.000 claims description 107
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000005418 aryl aryl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 284
- 239000005557 antagonist Substances 0.000 abstract description 10
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 208000020016 psychiatric disease Diseases 0.000 abstract description 3
- 150000003217 pyrazoles Chemical class 0.000 abstract description 3
- 230000000926 neurological effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 777
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 450
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 226
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 134
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 125
- 239000000243 solution Substances 0.000 description 109
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 108
- 229910021529 ammonia Inorganic materials 0.000 description 106
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
- 238000012799 strong cation exchange Methods 0.000 description 83
- 239000002904 solvent Substances 0.000 description 77
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 72
- 229910052786 argon Inorganic materials 0.000 description 67
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 53
- 238000003756 stirring Methods 0.000 description 46
- 238000010992 reflux Methods 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 31
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 235000019341 magnesium sulphate Nutrition 0.000 description 31
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 20
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 18
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- PEJXGIXLNJDHNZ-UHFFFAOYSA-N 6-benzyl-4,5,7,8-tetrahydro-1h-pyrazolo[3,4-d]azepine Chemical compound C1CC2=CNN=C2CCN1CC1=CC=CC=C1 PEJXGIXLNJDHNZ-UHFFFAOYSA-N 0.000 description 17
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 239000012298 atmosphere Substances 0.000 description 16
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
- 229960001340 histamine Drugs 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- KROXNGTXSOPSRS-UHFFFAOYSA-N 1-[4-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)phenyl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(N2N=C3CCNCCC3=C2)C=C1 KROXNGTXSOPSRS-UHFFFAOYSA-N 0.000 description 14
- 239000002808 molecular sieve Substances 0.000 description 14
- 125000002950 monocyclic group Chemical group 0.000 description 14
- 235000011181 potassium carbonates Nutrition 0.000 description 14
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 12
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- PJISIGKHCIEAKT-UHFFFAOYSA-N tert-butyl 4,5,7,8-tetrahydro-1h-pyrazolo[3,4-d]azepine-6-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC2=CNN=C21 PJISIGKHCIEAKT-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 10
- GRBXELGNDLKUOA-UHFFFAOYSA-N tert-butyl 2-(4-bromophenyl)-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6-carboxylate Chemical compound N1=C2CCN(C(=O)OC(C)(C)C)CCC2=CN1C1=CC=C(Br)C=C1 GRBXELGNDLKUOA-UHFFFAOYSA-N 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- ZKSLBQITPNATCT-UHFFFAOYSA-N 1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine Chemical compound C1CNCCC2=C1NN=C2 ZKSLBQITPNATCT-UHFFFAOYSA-N 0.000 description 8
- BZQUQLBDAKYDCX-UHFFFAOYSA-N 1-[4-(6-benzyl-4,5,7,8-tetrahydropyrazolo[3,4-d]azepin-2-yl)phenyl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(N2N=C3CCN(CC=4C=CC=CC=4)CCC3=C2)C=C1 BZQUQLBDAKYDCX-UHFFFAOYSA-N 0.000 description 8
- TVUIYWDZNFGFTC-UHFFFAOYSA-N 1-benzyl-5-chloro-2,3,6,7-tetrahydroazepine-4-carbaldehyde Chemical compound C1CC(Cl)=C(C=O)CCN1CC1=CC=CC=C1 TVUIYWDZNFGFTC-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- FYDZIWMYRVUMCV-UHFFFAOYSA-N 1-[5-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)pyridin-2-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(N2N=C3CCNCCC3=C2)C=N1 FYDZIWMYRVUMCV-UHFFFAOYSA-N 0.000 description 7
- JTPZTKBRUCILQD-UHFFFAOYSA-N 1-methylimidazolidin-2-one Chemical compound CN1CCNC1=O JTPZTKBRUCILQD-UHFFFAOYSA-N 0.000 description 7
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 7
- 102000004384 Histamine H3 receptors Human genes 0.000 description 7
- 108090000981 Histamine H3 receptors Proteins 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 7
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 6
- BZJQQRCFYKSQKX-UHFFFAOYSA-N 1-(5-bromopyridin-2-yl)pyrrolidin-2-one Chemical compound N1=CC(Br)=CC=C1N1C(=O)CCC1 BZJQQRCFYKSQKX-UHFFFAOYSA-N 0.000 description 6
- JXMRRRVOKOPLCD-UHFFFAOYSA-N 1-[5-(6-benzyl-4,5,7,8-tetrahydropyrazolo[3,4-d]azepin-2-yl)pyridin-2-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(N2N=C3CCN(CC=4C=CC=CC=4)CCC3=C2)C=N1 JXMRRRVOKOPLCD-UHFFFAOYSA-N 0.000 description 6
- WBYWWQLHAXLGPX-UHFFFAOYSA-N 1-methyl-3-[4-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)phenyl]imidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(N2N=C3CCNCCC3=C2)C=C1 WBYWWQLHAXLGPX-UHFFFAOYSA-N 0.000 description 6
- SOAXOIPIFFFTDI-UHFFFAOYSA-N 2-(4-bromophenyl)-6-cyclobutyl-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine Chemical compound C1=CC(Br)=CC=C1N1N=C2CCN(C3CCC3)CCC2=C1 SOAXOIPIFFFTDI-UHFFFAOYSA-N 0.000 description 6
- GEZKKYDMBPHUKG-UHFFFAOYSA-N 3-[4-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)phenyl]-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=C(N2N=C3CCNCCC3=C2)C=C1 GEZKKYDMBPHUKG-UHFFFAOYSA-N 0.000 description 6
- ZKJHVKPOOLTPHQ-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1N1N=C2CCNCCC2=C1 ZKJHVKPOOLTPHQ-UHFFFAOYSA-N 0.000 description 6
- JVLPSIRKUZEJDS-UHFFFAOYSA-N 6-benzyl-2-(4-bromophenyl)-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine Chemical compound C1=CC(Br)=CC=C1N1N=C2CCN(CC=3C=CC=CC=3)CCC2=C1 JVLPSIRKUZEJDS-UHFFFAOYSA-N 0.000 description 6
- YYZKXMYZEYHQLX-UHFFFAOYSA-N 6-cyclobutyl-4,5,7,8-tetrahydro-1h-pyrazolo[3,4-d]azepine Chemical compound C1CCC1N1CCC2=NNC=C2CC1 YYZKXMYZEYHQLX-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 239000005864 Sulphur Chemical group 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 125000001246 bromo group Chemical group Br* 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 238000005342 ion exchange Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 6
- LDUGHRZZTQLJNI-UHFFFAOYSA-N n-methyl-4-(5,6,7,8-tetrahydro-4h-pyrazolo[3,4-d]azepin-2-yl)benzamide Chemical compound C1=CC(C(=O)NC)=CC=C1N1N=C2CCNCCC2=C1 LDUGHRZZTQLJNI-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 201000003631 narcolepsy Diseases 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
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000005880 oxathiolanyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000012950 reanalysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000011808 rodent model 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
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- PMLBUVZPRKXMOX-UHFFFAOYSA-N tert-butyl 4-oxoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)CC1 PMLBUVZPRKXMOX-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 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
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0513886.2 | 2005-07-06 | ||
| GBGB0513886.2A GB0513886D0 (en) | 2005-07-06 | 2005-07-06 | Novel compounds |
| PCT/EP2006/006613 WO2007025596A1 (en) | 2005-07-06 | 2006-07-04 | Pyrazolo [3 , 4-d] azepine derivatives as histamine h3 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2614232A1 true CA2614232A1 (en) | 2007-03-08 |
Family
ID=34856781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002614232A Abandoned CA2614232A1 (en) | 2005-07-06 | 2006-07-04 | Pyrazolo [3,4-d] azepine derivatives as histamine h3 antagonists |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7888347B2 (OSRAM) |
| EP (1) | EP1899350B1 (OSRAM) |
| JP (1) | JP5145218B2 (OSRAM) |
| KR (1) | KR20080037651A (OSRAM) |
| CN (1) | CN101258154B (OSRAM) |
| AT (1) | ATE467636T1 (OSRAM) |
| AU (1) | AU2006286897A1 (OSRAM) |
| BR (1) | BRPI0612719A2 (OSRAM) |
| CA (1) | CA2614232A1 (OSRAM) |
| CR (1) | CR9622A (OSRAM) |
| CY (1) | CY1110711T1 (OSRAM) |
| DE (1) | DE602006014273D1 (OSRAM) |
| DK (1) | DK1899350T3 (OSRAM) |
| EA (1) | EA013600B1 (OSRAM) |
| ES (1) | ES2345841T3 (OSRAM) |
| GB (1) | GB0513886D0 (OSRAM) |
| HR (1) | HRP20100401T1 (OSRAM) |
| IL (1) | IL188184A0 (OSRAM) |
| MA (1) | MA29623B1 (OSRAM) |
| MX (1) | MX2008000383A (OSRAM) |
| NO (1) | NO20080563L (OSRAM) |
| PL (1) | PL1899350T3 (OSRAM) |
| PT (1) | PT1899350E (OSRAM) |
| SI (1) | SI1899350T1 (OSRAM) |
| UA (1) | UA93047C2 (OSRAM) |
| WO (1) | WO2007025596A1 (OSRAM) |
| ZA (1) | ZA200710798B (OSRAM) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
| US8829041B2 (en) | 2006-06-23 | 2014-09-09 | Abbvie Inc. | Cyclopropyl amine derivatives |
| MX2010002938A (es) | 2007-09-24 | 2010-04-01 | Comentis Inc | Derivados de (3-hidroxi-4-amino-butan-2-il)-3-(2-tiazol-2-il-pirro lidin-1-carbonil)benzamida y compuestos relacionados como inhibidores de beta-secretasa para tratar enfermedad de alzheimer. |
| US9186353B2 (en) * | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
| WO2012037258A1 (en) | 2010-09-16 | 2012-03-22 | Abbott Laboratories | Processes for preparing 1,2-substituted cyclopropyl derivatives |
| CN102952139B (zh) * | 2011-08-30 | 2016-08-10 | 上海药明康德新药开发有限公司 | 反式-3a-氟吡咯烷[3,4-C]并环化合物及其制备方法 |
| WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
| EP2647377A1 (en) | 2012-04-06 | 2013-10-09 | Sanofi | Use of an h3 receptor antagonist for the treatment of alzheimer's disease |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| US9910887B2 (en) * | 2013-04-25 | 2018-03-06 | Facebook, Inc. | Variable search query vertical access |
| BR112018074231A2 (pt) * | 2016-05-25 | 2019-03-06 | Akarna Therapeutics, Ltd. | compostos bicíclicos fundidos para o tratamento de doença |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6573218B1 (en) * | 1998-09-09 | 2003-06-03 | Ishihara Sangyo Kaisha, Ltd. | Fused-benzene derivatives useful as herbicides |
| EP1173438A1 (en) * | 1999-04-16 | 2002-01-23 | Novo Nordisk A/S | Substituted imidazoles, their preparation and use |
| JP2001220390A (ja) | 2000-02-09 | 2001-08-14 | Yamanouchi Pharmaceut Co Ltd | 縮合ピラゾール誘導体 |
| DE60312328T2 (de) * | 2002-06-06 | 2007-11-08 | Novo Nordisk A/S | Substituierte hexahydropyrrolo(1,2-a)pyrazine, octahydropyrido(1,2-a)pyrazine und decahydropyrazino(1,2-a)azepine |
| US6770597B2 (en) | 2002-07-17 | 2004-08-03 | Ishihara Sangyo Kaisha, Ltd. | Benzohydrazide derivatives as herbicides and desiccant compositions containing them |
| AU2003244649A1 (en) | 2002-07-25 | 2004-02-23 | Pharmacia Italia Spa | Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| EP1539704A1 (en) * | 2002-08-20 | 2005-06-15 | Eli Lilly And Company | Substituted azepines as histamine h3 receptor antagonists, preparation and therapeutic uses |
| GB0224083D0 (en) | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| GB0224557D0 (en) | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| ATE441417T1 (de) | 2002-12-20 | 2009-09-15 | Glaxo Group Ltd | Benzoädüazepinderivate für die behandlung von neurologischen krankheiten |
| AU2004283196B2 (en) * | 2003-09-17 | 2011-08-25 | Janssen Pharmaceutica, N.V. | Fused heterocyclic compounds |
| GB0329214D0 (en) | 2003-12-17 | 2004-01-21 | Glaxo Group Ltd | Novel compounds |
| GB0405628D0 (en) | 2004-03-12 | 2004-04-21 | Glaxo Group Ltd | Novel compounds |
| GB0408083D0 (en) | 2004-04-08 | 2004-05-12 | Glaxo Group Ltd | Novel compounds |
| US20070232590A1 (en) | 2004-06-18 | 2007-10-04 | Glaxo Group Limited | 3-Cylcoalkylbenzazepines as Histamine H3 Antagonists |
| GB0418267D0 (en) | 2004-08-16 | 2004-09-15 | Glaxo Group Ltd | Novel compounds |
| AU2005313550A1 (en) | 2004-12-07 | 2006-06-15 | Glaxo Group Limited | Indenyl derivatives and use thereof for the treatment of neurological disorders |
| EP1858900B1 (en) | 2005-03-14 | 2009-01-07 | Glaxo Group Limited | Fused thiazole derivatives having affinity for the histamine h3 receptor |
-
2005
- 2005-07-06 GB GBGB0513886.2A patent/GB0513886D0/en not_active Ceased
-
2006
- 2006-07-04 BR BRPI0612719-3A patent/BRPI0612719A2/pt not_active IP Right Cessation
- 2006-07-04 AU AU2006286897A patent/AU2006286897A1/en not_active Abandoned
- 2006-07-04 EP EP06818218A patent/EP1899350B1/en active Active
- 2006-07-04 HR HR20100401T patent/HRP20100401T1/hr unknown
- 2006-07-04 JP JP2008519862A patent/JP5145218B2/ja not_active Expired - Fee Related
- 2006-07-04 DK DK06818218.7T patent/DK1899350T3/da active
- 2006-07-04 US US11/994,689 patent/US7888347B2/en not_active Expired - Fee Related
- 2006-07-04 DE DE602006014273T patent/DE602006014273D1/de active Active
- 2006-07-04 PT PT06818218T patent/PT1899350E/pt unknown
- 2006-07-04 UA UAA200800190A patent/UA93047C2/ru unknown
- 2006-07-04 ES ES06818218T patent/ES2345841T3/es active Active
- 2006-07-04 CA CA002614232A patent/CA2614232A1/en not_active Abandoned
- 2006-07-04 MX MX2008000383A patent/MX2008000383A/es active IP Right Grant
- 2006-07-04 EA EA200800264A patent/EA013600B1/ru not_active IP Right Cessation
- 2006-07-04 KR KR1020087000265A patent/KR20080037651A/ko not_active Ceased
- 2006-07-04 SI SI200630733T patent/SI1899350T1/sl unknown
- 2006-07-04 CN CN2006800322776A patent/CN101258154B/zh not_active Expired - Fee Related
- 2006-07-04 AT AT06818218T patent/ATE467636T1/de active
- 2006-07-04 PL PL06818218T patent/PL1899350T3/pl unknown
- 2006-07-04 WO PCT/EP2006/006613 patent/WO2007025596A1/en not_active Ceased
-
2007
- 2007-12-12 ZA ZA200710798A patent/ZA200710798B/xx unknown
- 2007-12-17 IL IL188184A patent/IL188184A0/en unknown
- 2007-12-20 CR CR9622A patent/CR9622A/es not_active Application Discontinuation
-
2008
- 2008-01-09 MA MA30562A patent/MA29623B1/fr unknown
- 2008-01-30 NO NO20080563A patent/NO20080563L/no not_active Application Discontinuation
-
2010
- 2010-07-29 CY CY20101100713T patent/CY1110711T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0612719A2 (pt) | 2010-11-30 |
| CR9622A (es) | 2008-04-10 |
| US7888347B2 (en) | 2011-02-15 |
| JP5145218B2 (ja) | 2013-02-13 |
| UA93047C2 (ru) | 2011-01-10 |
| WO2007025596A1 (en) | 2007-03-08 |
| ATE467636T1 (de) | 2010-05-15 |
| DE602006014273D1 (de) | 2010-06-24 |
| JP2009500366A (ja) | 2009-01-08 |
| EP1899350B1 (en) | 2010-05-12 |
| ZA200710798B (en) | 2008-11-26 |
| EA200800264A1 (ru) | 2008-06-30 |
| EP1899350A1 (en) | 2008-03-19 |
| SI1899350T1 (sl) | 2010-09-30 |
| CN101258154A (zh) | 2008-09-03 |
| US20080176832A1 (en) | 2008-07-24 |
| AU2006286897A1 (en) | 2007-03-08 |
| IL188184A0 (en) | 2008-03-20 |
| KR20080037651A (ko) | 2008-04-30 |
| EA013600B1 (ru) | 2010-06-30 |
| GB0513886D0 (en) | 2005-08-10 |
| ES2345841T3 (es) | 2010-10-04 |
| CY1110711T1 (el) | 2015-06-10 |
| MA29623B1 (fr) | 2008-07-01 |
| NO20080563L (no) | 2008-02-01 |
| MX2008000383A (es) | 2008-03-07 |
| PL1899350T3 (pl) | 2010-10-29 |
| DK1899350T3 (da) | 2010-09-06 |
| PT1899350E (pt) | 2010-07-21 |
| HRP20100401T1 (hr) | 2010-09-30 |
| CN101258154B (zh) | 2011-01-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20140221 |