JP2006504714A - イミダゾール−１−イルメチルピリダジン誘導体 - Google Patents
イミダゾール−１−イルメチルピリダジン誘導体 Download PDFInfo
- Publication number
- JP2006504714A JP2006504714A JP2004541111A JP2004541111A JP2006504714A JP 2006504714 A JP2006504714 A JP 2006504714A JP 2004541111 A JP2004541111 A JP 2004541111A JP 2004541111 A JP2004541111 A JP 2004541111A JP 2006504714 A JP2006504714 A JP 2006504714A
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- JP
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- Prior art keywords
- imidazol
- alkyl
- compound
- ylmethyl
- pyridazine
- 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.)
- Pending
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- GFSWLEBKUPUQNQ-UHFFFAOYSA-N 3-(imidazol-1-ylmethyl)pyridazine Chemical class C1=CN=CN1CC1=CC=CN=N1 GFSWLEBKUPUQNQ-UHFFFAOYSA-N 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 285
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 170
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 168
- 230000000694 effects Effects 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 31
- 229940079593 drug Drugs 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 102000005962 receptors Human genes 0.000 claims description 167
- 108020003175 receptors Proteins 0.000 claims description 167
- 239000000203 mixture Substances 0.000 claims description 82
- -1 nitro, cyano, amino Chemical group 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 208000019901 Anxiety disease Diseases 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 230000036506 anxiety Effects 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 208000019116 sleep disease Diseases 0.000 claims description 17
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 238000001525 receptor binding assay Methods 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 150000005215 alkyl ethers Chemical class 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 230000006403 short-term memory Effects 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 7
- NBIZUQFXKBAKFG-UHFFFAOYSA-N 6-chloro-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propylpyridazine Chemical compound CCCC1=CC(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 NBIZUQFXKBAKFG-UHFFFAOYSA-N 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 7
- ZOPGOOYPCJDDTM-UHFFFAOYSA-N 4,6-diethoxy-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazine Chemical compound N1=NC(OCC)=CC(OCC)=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 ZOPGOOYPCJDDTM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
- 230000007831 electrophysiology Effects 0.000 claims description 6
- 238000002001 electrophysiology Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- HMXLPNRAAUANNY-UHFFFAOYSA-N 6-chloro-3-[[2-(3-chloro-2,6-difluorophenyl)imidazol-1-yl]methyl]-4-methoxypyridazine Chemical compound COC1=CC(Cl)=NN=C1CN1C(C=2C(=C(Cl)C=CC=2F)F)=NC=C1 HMXLPNRAAUANNY-UHFFFAOYSA-N 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 238000000376 autoradiography Methods 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 230000007781 signaling event Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 4
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 4
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- NEAFURIKNKLQPN-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4,6-dimethoxypyridazine Chemical compound N1=NC(OC)=CC(OC)=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 NEAFURIKNKLQPN-UHFFFAOYSA-N 0.000 claims description 4
- RUAJXDPCBSTFRM-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyrimidin-2-ylpyridazine Chemical compound CCCC1=CC(C=2N=CC=CN=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 RUAJXDPCBSTFRM-UHFFFAOYSA-N 0.000 claims description 4
- AWJGWXXJQARIIX-UHFFFAOYSA-N 6-chloro-4-ethyl-3-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]pyridazine Chemical compound CCC1=CC(Cl)=NN=C1CN1C(C=2C=C(F)C=CC=2)=NC=C1 AWJGWXXJQARIIX-UHFFFAOYSA-N 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- RQQZYTLGTPFWTN-UHFFFAOYSA-N 1-[6-[[2-(3-chloro-2,6-difluorophenyl)imidazol-1-yl]methyl]-5-methoxypyridazin-3-yl]ethanone Chemical compound COC1=CC(C(C)=O)=NN=C1CN1C(C=2C(=C(Cl)C=CC=2F)F)=NC=C1 RQQZYTLGTPFWTN-UHFFFAOYSA-N 0.000 claims description 3
- OSZONPVQLSYEQK-UHFFFAOYSA-N 2-[6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-propylpyridazin-3-yl]-1,3-thiazole Chemical compound CCCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 OSZONPVQLSYEQK-UHFFFAOYSA-N 0.000 claims description 3
- CAPNFIFKPASRGA-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyrazin-2-ylpyridazine Chemical compound CCCC1=CC(C=2N=CC=NC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 CAPNFIFKPASRGA-UHFFFAOYSA-N 0.000 claims description 3
- ISJUZYUIXPVLLP-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propylpyridazine Chemical compound CCCC1=CC=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 ISJUZYUIXPVLLP-UHFFFAOYSA-N 0.000 claims description 3
- LBGGKTDGGYJGSQ-UHFFFAOYSA-N 3-chloro-6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-methyl-5-propylpyridazine Chemical compound CCCC1=C(C)C(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 LBGGKTDGGYJGSQ-UHFFFAOYSA-N 0.000 claims description 3
- HMGOASIREUAWDZ-UHFFFAOYSA-N 4,6-diethoxy-3-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazine Chemical compound N1=NC(OCC)=CC(OCC)=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 HMGOASIREUAWDZ-UHFFFAOYSA-N 0.000 claims description 3
- JKAMQUDQAQOMNM-UHFFFAOYSA-N 4-ethoxy-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-methylpyridazine Chemical compound CCOC1=CC(C)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 JKAMQUDQAQOMNM-UHFFFAOYSA-N 0.000 claims description 3
- PWCVJNIHQROZBI-UHFFFAOYSA-N 6-chloro-4-ethoxy-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazine Chemical compound CCOC1=CC(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 PWCVJNIHQROZBI-UHFFFAOYSA-N 0.000 claims description 3
- SMQLGIJZHIDBNC-UHFFFAOYSA-N 6-chloro-n-ethyl-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazin-4-amine Chemical compound CCNC1=CC(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 SMQLGIJZHIDBNC-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 208000020685 sleep-wake disease Diseases 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- QIAFESKFECMFQS-UHFFFAOYSA-N 2-[5-ethyl-6-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]pyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=C1 QIAFESKFECMFQS-UHFFFAOYSA-N 0.000 claims description 2
- SFKBLJSNVUGLKL-UHFFFAOYSA-N 2-[5-ethyl-6-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=NC=CC=C1F SFKBLJSNVUGLKL-UHFFFAOYSA-N 0.000 claims description 2
- KJJBBNHTSNMNAY-UHFFFAOYSA-N 2-[5-ethyl-6-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]pyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC(F)=CC=C1C KJJBBNHTSNMNAY-UHFFFAOYSA-N 0.000 claims description 2
- JUVWXZDKVFTONQ-UHFFFAOYSA-N 2-[5-ethyl-6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 JUVWXZDKVFTONQ-UHFFFAOYSA-N 0.000 claims description 2
- FKTVSENZUYNFPF-UHFFFAOYSA-N 2-[6-[[2-(2,3-difluorophenyl)imidazol-1-yl]methyl]-5-ethylpyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=C1F FKTVSENZUYNFPF-UHFFFAOYSA-N 0.000 claims description 2
- GCLRPGMGLKHDFO-UHFFFAOYSA-N 2-[6-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-5-ethylpyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=CC(F)=CC=C1F GCLRPGMGLKHDFO-UHFFFAOYSA-N 0.000 claims description 2
- BBVBZYOWOGCUCH-UHFFFAOYSA-N 2-[6-[[2-(3-chloro-2,6-difluorophenyl)imidazol-1-yl]methyl]-5-ethylpyridazin-3-yl]-1,3-thiazole Chemical compound CCC1=CC(C=2SC=CN=2)=NN=C1CN1C=CN=C1C1=C(F)C=CC(Cl)=C1F BBVBZYOWOGCUCH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- QFZABYKBNVYAJC-UHFFFAOYSA-N 3-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyrimidin-5-ylpyridazine Chemical compound CCCC1=CC(C=2C=NC=NC=2)=NN=C1CN1C=CN=C1C1=NC=CC=C1F QFZABYKBNVYAJC-UHFFFAOYSA-N 0.000 claims description 2
- ADNLTWGXDNYFGC-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyridin-2-ylpyridazine Chemical compound CCCC1=CC(C=2N=CC=CC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 ADNLTWGXDNYFGC-UHFFFAOYSA-N 0.000 claims description 2
- KZJVWJFZDQVDND-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyridin-3-ylpyridazine Chemical compound CCCC1=CC(C=2C=NC=CC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 KZJVWJFZDQVDND-UHFFFAOYSA-N 0.000 claims description 2
- MVVWXWORNXLWRK-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propyl-6-pyridin-4-ylpyridazine Chemical compound CCCC1=CC(C=2C=CN=CC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 MVVWXWORNXLWRK-UHFFFAOYSA-N 0.000 claims description 2
- RRZOIBMOOQZJGG-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-methyl-4-propylpyridazine Chemical compound CCCC1=C(C)C=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 RRZOIBMOOQZJGG-UHFFFAOYSA-N 0.000 claims description 2
- WMJDRDHDHKBRSU-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-methyl-4-propylpyridazine Chemical compound CCCC1=CC(C)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 WMJDRDHDHKBRSU-UHFFFAOYSA-N 0.000 claims description 2
- QBXIBRWDHHEBIK-UHFFFAOYSA-N 4-ethoxy-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-pyridin-3-ylpyridazine Chemical compound CCOC1=CC(C=2C=NC=CC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 QBXIBRWDHHEBIK-UHFFFAOYSA-N 0.000 claims description 2
- XCEIXMMIBCLSCS-UHFFFAOYSA-N 4-ethyl-3-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]-6-methoxypyridazine Chemical compound CCC1=CC(OC)=NN=C1CN1C(C=2C=C(F)C=CC=2)=NC=C1 XCEIXMMIBCLSCS-UHFFFAOYSA-N 0.000 claims description 2
- JEKLSRVVSIUEMU-UHFFFAOYSA-N 4-ethyl-3-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]-6-piperidin-1-ylpyridazine Chemical compound CCC1=CC(N2CCCCC2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=C1 JEKLSRVVSIUEMU-UHFFFAOYSA-N 0.000 claims description 2
- SUTFNFBTDRPYPB-UHFFFAOYSA-N 4-ethyl-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-pyridin-3-ylpyridazine Chemical compound CCC1=CC(C=2C=NC=CC=2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=N1 SUTFNFBTDRPYPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- ZEAHCERLTDWEKC-UHFFFAOYSA-N 6-chloro-3-[[2-(2,3-difluorophenyl)imidazol-1-yl]methyl]-4-ethylpyridazine Chemical compound CCC1=CC(Cl)=NN=C1CN1C(C=2C(=C(F)C=CC=2)F)=NC=C1 ZEAHCERLTDWEKC-UHFFFAOYSA-N 0.000 claims description 2
- HOLSMJQOVSSHLF-UHFFFAOYSA-N 6-chloro-3-[[2-(2,5-difluorophenyl)imidazol-1-yl]methyl]-4-ethylpyridazine Chemical compound CCC1=CC(Cl)=NN=C1CN1C(C=2C(=CC=C(F)C=2)F)=NC=C1 HOLSMJQOVSSHLF-UHFFFAOYSA-N 0.000 claims description 2
- OIKKGXFBODKDJV-UHFFFAOYSA-N 6-chloro-3-[[2-(3-chloro-2,6-difluorophenyl)imidazol-1-yl]methyl]-4-ethylpyridazine Chemical compound CCC1=CC(Cl)=NN=C1CN1C(C=2C(=C(Cl)C=CC=2F)F)=NC=C1 OIKKGXFBODKDJV-UHFFFAOYSA-N 0.000 claims description 2
- GXYRPICXYIDUTN-UHFFFAOYSA-N 6-chloro-3-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propylpyridazine Chemical compound CCCC1=CC(Cl)=NN=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 GXYRPICXYIDUTN-UHFFFAOYSA-N 0.000 claims description 2
- YCSYYDFFCXBFGE-UHFFFAOYSA-N 6-chloro-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-n-propylpyridazin-4-amine Chemical compound CCCNC1=CC(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 YCSYYDFFCXBFGE-UHFFFAOYSA-N 0.000 claims description 2
- JUTGZFOVBUSESE-UHFFFAOYSA-N 6-chloro-4-ethyl-3-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]pyridazine Chemical compound CCC1=CC(Cl)=NN=C1CN1C(C=2C(=CC=C(F)C=2)C)=NC=C1 JUTGZFOVBUSESE-UHFFFAOYSA-N 0.000 claims description 2
- BLSMIHGSXWMBJI-UHFFFAOYSA-N 6-chloro-n,n-diethyl-3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]pyridazin-4-amine Chemical compound CCN(CC)C1=CC(Cl)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 BLSMIHGSXWMBJI-UHFFFAOYSA-N 0.000 claims description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000004650 C1-C8 alkynyl group Chemical group 0.000 claims description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 10
- QWLRJSGZNUOFFH-UHFFFAOYSA-N 1-[5-ethyl-6-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]pyridazin-3-yl]piperidin-4-ol Chemical compound CCC1=CC(N2CCC(O)CC2)=NN=C1CN1C=CN=C1C1=CC=CC(F)=C1 QWLRJSGZNUOFFH-UHFFFAOYSA-N 0.000 claims 1
- YDQYUOBULGEHLF-UHFFFAOYSA-N 1-[6-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-propylpyridazin-3-yl]ethanone Chemical compound CCCC1=CC(C(C)=O)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 YDQYUOBULGEHLF-UHFFFAOYSA-N 0.000 claims 1
- BIYFUSPPTFUWGO-UHFFFAOYSA-N 3-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4-propylpyridazine Chemical compound CCCC1=CC=NN=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 BIYFUSPPTFUWGO-UHFFFAOYSA-N 0.000 claims 1
- ZFWNBYLIQPGCQB-UHFFFAOYSA-N 3-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-methoxy-4-propylpyridazine Chemical compound CCCC1=CC(OC)=NN=C1CN1C(C=2C(=CC=CN=2)F)=NC=C1 ZFWNBYLIQPGCQB-UHFFFAOYSA-N 0.000 claims 1
- XBNNILZFXIFMJM-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-4,6-dipropylpyridazine Chemical compound N1=NC(CCC)=CC(CCC)=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 XBNNILZFXIFMJM-UHFFFAOYSA-N 0.000 claims 1
- UOQITUWVHWFNIW-UHFFFAOYSA-N 3-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-6-(3-methoxyprop-1-ynyl)-4-propylpyridazine Chemical compound CCCC1=CC(C#CCOC)=NN=C1CN1C(C=2N=C(F)C=CC=2)=NC=C1 UOQITUWVHWFNIW-UHFFFAOYSA-N 0.000 claims 1
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- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41666002P | 2002-10-07 | 2002-10-07 | |
| PCT/IB2003/004382 WO2004031174A1 (en) | 2002-10-07 | 2003-10-06 | Imidazol-1-ylmethyl pyridazine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006504714A true JP2006504714A (ja) | 2006-02-09 |
| JP2006504714A5 JP2006504714A5 (https=) | 2006-11-16 |
Family
ID=32069951
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004541111A Pending JP2006504714A (ja) | 2002-10-07 | 2003-10-06 | イミダゾール−１−イルメチルピリダジン誘導体 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7122546B2 (https=) |
| EP (1) | EP1549636A1 (https=) |
| JP (1) | JP2006504714A (https=) |
| CN (1) | CN100579579C (https=) |
| AU (1) | AU2003267722A1 (https=) |
| CA (1) | CA2495698A1 (https=) |
| WO (1) | WO2004031174A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003276514A1 (en) * | 2002-11-08 | 2004-06-07 | Neurogen Corporation | 4-imidazol-1-ylmethyl-pyrimidine derivatives_as ligands for gabaa receptors |
| EP1594848A1 (en) | 2003-02-19 | 2005-11-16 | Neurogen Corporation | Aryl acid pyrimidinyl methyl amides, pyridazinyl methyl amides and related compounds |
| BRPI0412908A (pt) * | 2003-07-25 | 2006-09-26 | Neurogen Corp | composto ou um sal deste farmaceuticamente aceitável, composição farmacêutica, métodos para o tratamento de ansiedade, depressão, um distúrbio do sono, distúrbio de déficit de atenção ou demência de alzheimer, para potenciar um efeito terapêutico de um agente do cns, para melhorar a memória de curta duração em um paciente, para alterar a atividade de transdução de sinal de receptor gabaa, e para determinar a presença ou ausência de receptor gabaa em uma amostra, preparação farmacêutica acondicionada, e, uso de um composto ou sal |
| BRPI0510929A (pt) | 2004-06-18 | 2007-07-17 | Chiron Corp | derivados de n-(1-(1-benzil-4-fenil-1h-imidazol-2-il)-2,2-dimetilpropil) benzamida e compostos relacionados como inibidores de proteìna de eixo de kinesin (ksp) para o tratamento de cáncer |
| WO2008086122A2 (en) | 2007-01-05 | 2008-07-17 | Novartis Ag | Imidazole derivatives as kinesin spindle protein inhibitors (eg-5) |
| KR20090111847A (ko) | 2007-01-19 | 2009-10-27 | 아디아 바이오사이언스즈 인크. | Ｍｅｋ 억제제 |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| RU2705556C2 (ru) * | 2012-12-21 | 2019-11-07 | Келверум Инк. | Нереплицируемые происходящие от вирусов частицы и их применение |
| JP7113023B2 (ja) | 2017-03-30 | 2022-08-04 | ブリストル－マイヤーズ スクイブ カンパニー | ６－（シクロプロパンアミド）－４－（（２－メトキシ－３－（１－メチル－１ｈ－１，２，４－トリアゾール－３－イル）フェニル）アミノ）－ｎ－（メチル－ｄ３）ピリダジン－３－カルボキシアミドの製造方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6200959B1 (en) * | 1996-12-04 | 2001-03-13 | Powerject Vaccines Inc. | Genetic induction of anti-viral immune response and genetic vaccine for filovirus |
| JP2002527401A (ja) * | 1998-10-13 | 2002-08-27 | カイロン コーポレイション | Ｆｇｆの脈管形成的に有効な単位用量および投与方法 |
| WO2002002557A2 (en) * | 2000-06-30 | 2002-01-10 | Neurogen Corporation | 2-phenylimidazo[1,2-a]pyridine derivatives: a new class of gaba brain receptor ligands |
| PA8535601A1 (es) * | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| WO2004041809A2 (en) * | 2002-05-08 | 2004-05-21 | Neurogen Corporation | Substituted imidazolylmethyl pyridine and pyrazine derivatives and their use as gabaa receptor ligands |
| US7005432B2 (en) * | 2002-05-16 | 2006-02-28 | Hoffman-La Roche Inc. | Substituted imidazol-pyridazine derivatives |
| AU2003276514A1 (en) | 2002-11-08 | 2004-06-07 | Neurogen Corporation | 4-imidazol-1-ylmethyl-pyrimidine derivatives_as ligands for gabaa receptors |
| US20060247245A1 (en) | 2003-05-05 | 2006-11-02 | Yuelian Xu | Substituted imidazolopyrazine and triazolopyrazine derivatives: gabaa receptor ligands |
-
2003
- 2003-10-01 CN CN200380104308A patent/CN100579579C/zh not_active Expired - Fee Related
- 2003-10-06 CA CA002495698A patent/CA2495698A1/en not_active Abandoned
- 2003-10-06 JP JP2004541111A patent/JP2006504714A/ja active Pending
- 2003-10-06 WO PCT/IB2003/004382 patent/WO2004031174A1/en not_active Ceased
- 2003-10-06 AU AU2003267722A patent/AU2003267722A1/en not_active Abandoned
- 2003-10-06 EP EP03748416A patent/EP1549636A1/en not_active Withdrawn
- 2003-10-07 US US10/680,351 patent/US7122546B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004031174A1 (en) | 2004-04-15 |
| CN100579579C (zh) | 2010-01-13 |
| CN1717250A (zh) | 2006-01-04 |
| WO2004031174A8 (en) | 2005-04-21 |
| EP1549636A1 (en) | 2005-07-06 |
| CA2495698A1 (en) | 2004-04-15 |
| AU2003267722A8 (en) | 2004-04-23 |
| US7122546B2 (en) | 2006-10-17 |
| AU2003267722A1 (en) | 2004-04-23 |
| US20040077653A1 (en) | 2004-04-22 |
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