JP2008533117A - ヒスタミンｈ３受容体に対して親和性を有する縮合チアゾール誘導体 - Google Patents
ヒスタミンｈ３受容体に対して親和性を有する縮合チアゾール誘導体 Download PDFInfo
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- JP2008533117A JP2008533117A JP2008501397A JP2008501397A JP2008533117A JP 2008533117 A JP2008533117 A JP 2008533117A JP 2008501397 A JP2008501397 A JP 2008501397A JP 2008501397 A JP2008501397 A JP 2008501397A JP 2008533117 A JP2008533117 A JP 2008533117A
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- JP
- Japan
- Prior art keywords
- alkyl
- mmol
- tetrahydro
- thiazolo
- cyclobutyl
- 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.)
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- 150000007979 thiazole derivatives Chemical class 0.000 title abstract description 3
- 102000004384 Histamine H3 receptors Human genes 0.000 title description 8
- 108090000981 Histamine H3 receptors Proteins 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 102
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 166
- 150000001875 compounds Chemical class 0.000 claims description 98
- 125000001072 heteroaryl group Chemical group 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 57
- -1 hydroxy, cyano, amino Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 150000002367 halogens Chemical class 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 239000012453 solvate Substances 0.000 claims description 22
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- WUFMUYFEWPBICZ-UHFFFAOYSA-N 5-[3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidin-1-yl]pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1N1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 WUFMUYFEWPBICZ-UHFFFAOYSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- DXAMKIWWMUKGFJ-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 DXAMKIWWMUKGFJ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- MXNROENSEHWVOE-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(5-methylpyridin-3-yl)methanone Chemical compound CC1=CN=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 MXNROENSEHWVOE-UHFFFAOYSA-N 0.000 claims description 6
- FTVIUIXLKVOCFD-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(6-methylpyridin-2-yl)methanone Chemical compound CC1=CC=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 FTVIUIXLKVOCFD-UHFFFAOYSA-N 0.000 claims description 6
- VZWORUHCRUFYEY-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 VZWORUHCRUFYEY-UHFFFAOYSA-N 0.000 claims description 5
- AVGWDAZNMDHRLW-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-n,n-dimethylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)N(C)C)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 AVGWDAZNMDHRLW-UHFFFAOYSA-N 0.000 claims description 5
- BZIMEWAWRGVTEM-UHFFFAOYSA-N 6-cyclobutyl-2-[1-(6-methylpyridin-3-yl)pyrrolidin-3-yl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(C)=CC=C1N1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 BZIMEWAWRGVTEM-UHFFFAOYSA-N 0.000 claims description 5
- GVFNIRHEMHBGKK-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 GVFNIRHEMHBGKK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- RVMLJMMOHPMSBM-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]imidazolidin-2-one Chemical compound O=C1NCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 RVMLJMMOHPMSBM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 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
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 262
- 208000020016 psychiatric disease Diseases 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 208000025966 Neurological disease Diseases 0.000 abstract 1
- 230000000926 neurological effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 681
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 273
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 218
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 128
- 239000000243 solution Substances 0.000 description 128
- 239000000047 product Substances 0.000 description 115
- 229910021529 ammonia Inorganic materials 0.000 description 109
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 82
- 238000010992 reflux Methods 0.000 description 79
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- 238000005342 ion exchange Methods 0.000 description 69
- 229910052786 argon Inorganic materials 0.000 description 64
- 238000003756 stirring Methods 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 238000010898 silica gel chromatography Methods 0.000 description 39
- 239000002904 solvent Substances 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 32
- 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 30
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- VFHJFPGGWIXTMI-UHFFFAOYSA-N 6-cyclobutyl-2-piperidin-4-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CCNCC3)=C2CC1 VFHJFPGGWIXTMI-UHFFFAOYSA-N 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- VLTPTYUTFLPHFK-UHFFFAOYSA-N 2,2,2-trifluoro-1-(2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl)ethanone Chemical compound C1CN(C(=O)C(F)(F)F)CCC2=C1SC(I)=N2 VLTPTYUTFLPHFK-UHFFFAOYSA-N 0.000 description 17
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 16
- 229960001340 histamine Drugs 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 15
- 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 14
- NGKHTLLTBXIGQX-UHFFFAOYSA-N 1-[2-(6-chloropyridin-3-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl]-2,2,2-trifluoroethanone Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C1=CC=C(Cl)N=C1 NGKHTLLTBXIGQX-UHFFFAOYSA-N 0.000 description 14
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 14
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 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 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 239000005557 antagonist Substances 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- XHOGXAKOVBDTCY-UHFFFAOYSA-N 1-cyclobutylazepan-4-one Chemical compound C1CC(=O)CCCN1C1CCC1 XHOGXAKOVBDTCY-UHFFFAOYSA-N 0.000 description 11
- YXCBMVKTMYRQHH-UHFFFAOYSA-N 2-(4-bromophenyl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=CC(Br)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 YXCBMVKTMYRQHH-UHFFFAOYSA-N 0.000 description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- SOSZRSSOEUVNSJ-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 SOSZRSSOEUVNSJ-UHFFFAOYSA-N 0.000 description 10
- MQEVKGXAHHFTOC-UHFFFAOYSA-N 6-cyclobutyl-2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CC=2SC(I)=NC=2CCN1C1CCC1 MQEVKGXAHHFTOC-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
- NQULAAUVWPUYMT-UHFFFAOYSA-N 6-cyclobutyl-2-pyrrolidin-3-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CNCC3)=C2CC1 NQULAAUVWPUYMT-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 125000002950 monocyclic group Chemical group 0.000 description 9
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- GYBIVLSDYIABQH-UHFFFAOYSA-N (6-chloropyridin-3-yl)-trimethylstannane Chemical compound C[Sn](C)(C)C1=CC=C(Cl)N=C1 GYBIVLSDYIABQH-UHFFFAOYSA-N 0.000 description 8
- BSEBWOQMJFGBDM-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCNCC2 BSEBWOQMJFGBDM-UHFFFAOYSA-N 0.000 description 8
- BLBFCFLWAMYCME-UHFFFAOYSA-N 2h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC=CC2=NCSC2=C1 BLBFCFLWAMYCME-UHFFFAOYSA-N 0.000 description 8
- DSLIOSJHXFXKLW-UHFFFAOYSA-N 5-bromo-1-cyclobutylazepan-4-one Chemical compound C1CC(=O)C(Br)CCN1C1CCC1 DSLIOSJHXFXKLW-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 8
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- LOMSQGIKFZLYTD-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 LOMSQGIKFZLYTD-UHFFFAOYSA-N 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- ZSPHQFZPSFCXIX-UHFFFAOYSA-N 2-iodo-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CNCCC2=C1N=C(I)S2 ZSPHQFZPSFCXIX-UHFFFAOYSA-N 0.000 description 6
- 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
- NWISRHCDYAIVGL-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 NWISRHCDYAIVGL-UHFFFAOYSA-N 0.000 description 6
- INCVZKRMUFWNJO-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-1H-pyrimidin-2-one Chemical compound N1C(=O)N=CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 INCVZKRMUFWNJO-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0505205A GB0505205D0 (en) | 2005-03-14 | 2005-03-14 | Novel compounds |
| GB0525239A GB0525239D0 (en) | 2005-12-12 | 2005-12-12 | Novel compounds |
| PCT/GB2006/000846 WO2006097691A1 (en) | 2005-03-14 | 2006-03-10 | Fused thiazole derivatives having affinity for the histamine h3 receptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008533117A true JP2008533117A (ja) | 2008-08-21 |
| JP2008533117A5 JP2008533117A5 (enExample) | 2009-04-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008501397A Withdrawn JP2008533117A (ja) | 2005-03-14 | 2006-03-10 | ヒスタミンｈ３受容体に対して親和性を有する縮合チアゾール誘導体 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20080161289A1 (enExample) |
| EP (1) | EP1858900B1 (enExample) |
| JP (1) | JP2008533117A (enExample) |
| KR (1) | KR20070113225A (enExample) |
| AT (1) | ATE420091T1 (enExample) |
| AU (1) | AU2006224440A1 (enExample) |
| BR (1) | BRPI0608437A2 (enExample) |
| CA (1) | CA2601644A1 (enExample) |
| DE (1) | DE602006004714D1 (enExample) |
| EA (1) | EA200701984A1 (enExample) |
| ES (1) | ES2321028T3 (enExample) |
| IL (1) | IL185869A0 (enExample) |
| MA (1) | MA29339B1 (enExample) |
| MX (1) | MX2007011211A (enExample) |
| NO (1) | NO20074977L (enExample) |
| WO (1) | WO2006097691A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013536834A (ja) * | 2010-09-02 | 2013-09-26 | スヴェン ライフ サイエンシズ リミテッド | ヒスタミンｈ３受容体リガンドとしてのヘテロシクリル化合物 |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0513886D0 (en) | 2005-07-06 | 2005-08-10 | Glaxo Group Ltd | Novel compounds |
| US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
| CN101472887A (zh) | 2006-06-23 | 2009-07-01 | 艾博特公司 | 作为组胺h3受体调节物的环丙胺衍生物 |
| US8283360B2 (en) | 2008-12-19 | 2012-10-09 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic derivatives and methods of use thereof |
| US20110245267A1 (en) * | 2008-12-19 | 2011-10-06 | Schering Plough Corporation | Piperidine and piperazine derivatives and methods of use thereof |
| 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 |
| 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 |
| US10662157B2 (en) | 2016-04-06 | 2020-05-26 | Sumitomo Chemical Company, Limited | Heterocyclic compound |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4324580A1 (de) * | 1993-07-22 | 1995-01-26 | Thomae Gmbh Dr K | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4427838A1 (de) | 1994-08-05 | 1996-02-08 | Thomae Gmbh Dr K | Kondensierte Azepinderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| JPH1017569A (ja) | 1996-07-05 | 1998-01-20 | Yamanouchi Pharmaceut Co Ltd | 置換チアゾール誘導体を有効成分とする医薬及び新規化合物 |
| EP1173438A1 (en) | 1999-04-16 | 2002-01-23 | Novo Nordisk A/S | Substituted imidazoles, their preparation and use |
| GB0224083D0 (en) | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| US8466143B2 (en) | 2003-07-23 | 2013-06-18 | Exelixis, Inc. | Azepine derivatives as pharmaceutical agents |
-
2006
- 2006-03-10 ES ES06710058T patent/ES2321028T3/es active Active
- 2006-03-10 WO PCT/GB2006/000846 patent/WO2006097691A1/en not_active Ceased
- 2006-03-10 US US11/908,532 patent/US20080161289A1/en not_active Abandoned
- 2006-03-10 KR KR1020077020994A patent/KR20070113225A/ko not_active Withdrawn
- 2006-03-10 AT AT06710058T patent/ATE420091T1/de not_active IP Right Cessation
- 2006-03-10 MX MX2007011211A patent/MX2007011211A/es unknown
- 2006-03-10 JP JP2008501397A patent/JP2008533117A/ja not_active Withdrawn
- 2006-03-10 EA EA200701984A patent/EA200701984A1/ru unknown
- 2006-03-10 CA CA002601644A patent/CA2601644A1/en not_active Abandoned
- 2006-03-10 AU AU2006224440A patent/AU2006224440A1/en not_active Abandoned
- 2006-03-10 BR BRPI0608437-0A patent/BRPI0608437A2/pt not_active IP Right Cessation
- 2006-03-10 DE DE602006004714T patent/DE602006004714D1/de active Active
- 2006-03-10 EP EP06710058A patent/EP1858900B1/en active Active
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2007
- 2007-09-10 IL IL185869A patent/IL185869A0/en unknown
- 2007-09-24 MA MA30235A patent/MA29339B1/fr unknown
- 2007-10-02 NO NO20074977A patent/NO20074977L/no not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013536834A (ja) * | 2010-09-02 | 2013-09-26 | スヴェン ライフ サイエンシズ リミテッド | ヒスタミンｈ３受容体リガンドとしてのヘテロシクリル化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20080161289A1 (en) | 2008-07-03 |
| CA2601644A1 (en) | 2006-09-21 |
| EP1858900B1 (en) | 2009-01-07 |
| MA29339B1 (fr) | 2008-03-03 |
| MX2007011211A (es) | 2007-10-17 |
| AU2006224440A1 (en) | 2006-09-21 |
| ATE420091T1 (de) | 2009-01-15 |
| EA200701984A1 (ru) | 2008-02-28 |
| DE602006004714D1 (de) | 2009-02-26 |
| EP1858900A1 (en) | 2007-11-28 |
| IL185869A0 (en) | 2008-01-06 |
| KR20070113225A (ko) | 2007-11-28 |
| BRPI0608437A2 (pt) | 2009-12-29 |
| ES2321028T3 (es) | 2009-06-01 |
| WO2006097691A1 (en) | 2006-09-21 |
| NO20074977L (no) | 2007-12-11 |
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