CA2601644A1 - Fused thiazole derivatives having affinity for the histamine h3 receptor - Google Patents
Fused thiazole derivatives having affinity for the histamine h3 receptor Download PDFInfo
- Publication number
- CA2601644A1 CA2601644A1 CA002601644A CA2601644A CA2601644A1 CA 2601644 A1 CA2601644 A1 CA 2601644A1 CA 002601644 A CA002601644 A CA 002601644A CA 2601644 A CA2601644 A CA 2601644A CA 2601644 A1 CA2601644 A1 CA 2601644A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- thiazolo
- tetrahydro
- cyclobutyl
- mixture
- 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
- 150000007979 thiazole derivatives Chemical class 0.000 title abstract description 4
- 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 118
- 230000008569 process Effects 0.000 claims abstract description 56
- 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 8
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 100
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- 125000001072 heteroaryl group Chemical group 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 57
- -1 hydroxy, cyano, amino Chemical group 0.000 claims description 57
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 150000002367 halogens Chemical group 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 239000012453 solvate Substances 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 11
- 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 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
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 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
- 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
- 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 5
- 239000003937 drug carrier Substances 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
- 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 4
- 101100134922 Gallus gallus COR5 gene Proteins 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
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 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 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 262
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 208000020016 psychiatric disease Diseases 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 675
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 279
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 218
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 137
- 239000000243 solution Substances 0.000 description 137
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 130
- 239000000047 product Substances 0.000 description 113
- 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
- 238000010992 reflux Methods 0.000 description 80
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- 238000012799 strong cation exchange Methods 0.000 description 75
- 238000005342 ion exchange Methods 0.000 description 69
- 229910052786 argon Inorganic materials 0.000 description 65
- 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 40
- 238000010898 silica gel chromatography Methods 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 239000002904 solvent Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- 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 33
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- 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 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 20
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 19
- 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 19
- 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 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 18
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 229960001340 histamine Drugs 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 15
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 15
- 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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 239000005557 antagonist Substances 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- 239000004793 Polystyrene Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 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 10
- 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 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229920002223 polystyrene Polymers 0.000 description 10
- DSLIOSJHXFXKLW-UHFFFAOYSA-N 5-bromo-1-cyclobutylazepan-4-one Chemical compound C1CC(=O)C(Br)CCN1C1CCC1 DSLIOSJHXFXKLW-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 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
- XHOGXAKOVBDTCY-UHFFFAOYSA-N 1-cyclobutylazepan-4-one Chemical compound C1CC(=O)CCCN1C1CCC1 XHOGXAKOVBDTCY-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
- 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 8
- 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 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
- 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- 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 7
- 239000013058 crude material Substances 0.000 description 7
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- ZARMWDJPQZIACM-UHFFFAOYSA-N 6-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1C(S1)=NC2=C1CCNCC2 ZARMWDJPQZIACM-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- HYTTVKRGUYTJLN-UHFFFAOYSA-N tributyl-(6-chloropyridin-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(Cl)N=C1 HYTTVKRGUYTJLN-UHFFFAOYSA-N 0.000 description 6
- YNFHSHYLEKIMGJ-UHFFFAOYSA-N 1-(2,2,2-trifluoroacetyl)azepan-4-one Chemical compound FC(F)(F)C(=O)N1CCCC(=O)CC1 YNFHSHYLEKIMGJ-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
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- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
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- VDDMCMFPUSCJNA-UHFFFAOYSA-N tert-butyl 3-cyanopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C#N)C1 VDDMCMFPUSCJNA-UHFFFAOYSA-N 0.000 description 1
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- HJZYBDPHAHGHAZ-UHFFFAOYSA-N thiadiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSN=N1 HJZYBDPHAHGHAZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
-
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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Landscapes
- 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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0505205A GB0505205D0 (en) | 2005-03-14 | 2005-03-14 | Novel compounds |
| GB0505205.5 | 2005-03-14 | ||
| GB0525239.0 | 2005-12-12 | ||
| 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 (1)
| Publication Number | Publication Date |
|---|---|
| CA2601644A1 true CA2601644A1 (en) | 2006-09-21 |
Family
ID=36283759
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002601644A Abandoned CA2601644A1 (en) | 2005-03-14 | 2006-03-10 | Fused thiazole derivatives having affinity for the histamine h3 receptor |
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) |
Families Citing this family (11)
| 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 |
| HUE028435T2 (en) * | 2010-09-02 | 2016-12-28 | Suven Life Sciences Ltd | Heterocyclic compounds as histamine H3 receptor ligands |
| 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 |
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| 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 |
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2006
- 2006-03-10 ES ES06710058T patent/ES2321028T3/es active Active
- 2006-03-10 WO PCT/GB2006/000846 patent/WO2006097691A1/en not_active Ceased
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- 2006-03-10 KR KR1020077020994A patent/KR20070113225A/ko not_active Withdrawn
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- 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
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2007
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- 2007-09-24 MA MA30235A patent/MA29339B1/fr unknown
- 2007-10-02 NO NO20074977A patent/NO20074977L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| US20080161289A1 (en) | 2008-07-03 |
| 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 |
| JP2008533117A (ja) | 2008-08-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |