JP2007500130A - ベンゾジアゼピン受容体リガンドである、イミダゾ−ピリミジン及びトリアゾロ−ピリミジン - Google Patents
ベンゾジアゼピン受容体リガンドである、イミダゾ−ピリミジン及びトリアゾロ−ピリミジン Download PDFInfo
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- JP2007500130A JP2007500130A JP2006521278A JP2006521278A JP2007500130A JP 2007500130 A JP2007500130 A JP 2007500130A JP 2006521278 A JP2006521278 A JP 2006521278A JP 2006521278 A JP2006521278 A JP 2006521278A JP 2007500130 A JP2007500130 A JP 2007500130A
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- JP
- Japan
- Prior art keywords
- imidazol
- pyrimidine
- triazolo
- ylmethyl
- propyl
- 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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- 239000003446 ligand Substances 0.000 title abstract description 19
- 150000005237 imidazopyrimidines Chemical class 0.000 title description 5
- 102000004300 GABA-A Receptors Human genes 0.000 title description 2
- 108090000839 GABA-A Receptors Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 326
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 167
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 166
- 238000000034 method Methods 0.000 claims abstract description 58
- 230000027455 binding Effects 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 239000000556 agonist Substances 0.000 claims abstract description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- -1 nitro, cyano, amino Chemical group 0.000 claims description 159
- 102000005962 receptors Human genes 0.000 claims description 155
- 108020003175 receptors Proteins 0.000 claims description 155
- 239000000203 mixture Substances 0.000 claims description 91
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- 238000012360 testing method Methods 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 63
- 125000001424 substituent group Chemical group 0.000 claims description 63
- 150000002367 halogens Chemical class 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 53
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 125000001188 haloalkyl group Chemical group 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 239000000523 sample Substances 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 22
- 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 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 208000019901 Anxiety disease Diseases 0.000 claims description 20
- 208000019116 sleep disease Diseases 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 230000036506 anxiety Effects 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical compound NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 10
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 10
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 9
- 230000006403 short-term memory Effects 0.000 claims description 8
- HRETYXMMIJBZRN-UHFFFAOYSA-N 6-[1-[(8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]pyridine-2-carbonitrile Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(C#N)=N1 HRETYXMMIJBZRN-UHFFFAOYSA-N 0.000 claims description 7
- IJZQSEGBLMAYSB-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-2-pyrrolidin-1-yl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(N3CCCC3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F IJZQSEGBLMAYSB-UHFFFAOYSA-N 0.000 claims description 7
- 208000000044 Amnesia Diseases 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- UYUZKXAGLYQINB-UHFFFAOYSA-N 2-[1-[(8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]pyridine-3-carbonitrile Chemical compound N1=CN2N=CN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1C#N UYUZKXAGLYQINB-UHFFFAOYSA-N 0.000 claims description 6
- IPXNSCRXLXHBIZ-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-methyl-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=C(C)N2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 IPXNSCRXLXHBIZ-UHFFFAOYSA-N 0.000 claims description 6
- CDFFJLUXSUAEDN-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CC(F)F)=C1CN1C=CN=C1C1=NC=CC=C1F CDFFJLUXSUAEDN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 238000000376 autoradiography Methods 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 230000007781 signaling event Effects 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- DQSXIULXVLEYIP-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-propan-2-yloxy-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(OC(C)C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F DQSXIULXVLEYIP-UHFFFAOYSA-N 0.000 claims description 5
- UWTLXBIEGTWTMZ-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-2-carbonitrile Chemical compound N1=CN2C=C(C#N)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 UWTLXBIEGTWTMZ-UHFFFAOYSA-N 0.000 claims description 5
- 150000005215 alkyl ethers Chemical class 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000013068 control sample Substances 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 208000020685 sleep-wake disease Diseases 0.000 claims description 5
- HMHIPFOQWVGGCP-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F HMHIPFOQWVGGCP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- 238000001525 receptor binding assay Methods 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- CIAROHKHYKMXOX-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-1-methyl-8-propylimidazo[1,5-c]pyrimidine Chemical compound N1=CN2C=NC(C)=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CIAROHKHYKMXOX-UHFFFAOYSA-N 0.000 claims description 3
- JPOKMXYVDZDHCA-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-3-carbonitrile Chemical compound N1=CN2C(C#N)=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 JPOKMXYVDZDHCA-UHFFFAOYSA-N 0.000 claims description 3
- GBQVPQANRQCFKU-UHFFFAOYSA-N 8-ethyl-7-[[2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C=NN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(C(F)(F)F)=C1 GBQVPQANRQCFKU-UHFFFAOYSA-N 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 3
- 230000007831 electrophysiology Effects 0.000 claims description 3
- 238000002001 electrophysiology Methods 0.000 claims description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- XLBLTGCZHQLTHS-UHFFFAOYSA-N 2-(fluoromethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CF)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F XLBLTGCZHQLTHS-UHFFFAOYSA-N 0.000 claims description 2
- VNRCPYKSCJJOCU-UHFFFAOYSA-N 3-(difluoromethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C(F)F)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F VNRCPYKSCJJOCU-UHFFFAOYSA-N 0.000 claims description 2
- ZEAWTFVUEKDYDK-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-phenyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C=3C=CC=CC=3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F ZEAWTFVUEKDYDK-UHFFFAOYSA-N 0.000 claims description 2
- BRFPCEPJPXZGDA-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-propan-2-yl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C(C)C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F BRFPCEPJPXZGDA-UHFFFAOYSA-N 0.000 claims description 2
- BSBGPAVQSMJLET-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-phenyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C=3C=CC=CC=3)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F BSBGPAVQSMJLET-UHFFFAOYSA-N 0.000 claims description 2
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 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
- 239000002775 capsule Substances 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- AHLZHYYIYJLVNC-UHFFFAOYSA-N ethyl 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine-2-carboxylate Chemical compound N1=CN2C=C(C(=O)OCC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 AHLZHYYIYJLVNC-UHFFFAOYSA-N 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 15
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- YMBCGEXQOACNHS-UHFFFAOYSA-N 2,8-diethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CC)N=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C YMBCGEXQOACNHS-UHFFFAOYSA-N 0.000 claims 1
- GKYYCIFMTQMTHX-UHFFFAOYSA-N 2-(difluoromethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C(F)F)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F GKYYCIFMTQMTHX-UHFFFAOYSA-N 0.000 claims 1
- IZSCGZKYJYEHCE-UHFFFAOYSA-N 2-(ethoxymethyl)-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(COCC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F IZSCGZKYJYEHCE-UHFFFAOYSA-N 0.000 claims 1
- SCGMXMDBDVEBET-UHFFFAOYSA-N 2-(ethoxymethyl)-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(COCC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 SCGMXMDBDVEBET-UHFFFAOYSA-N 0.000 claims 1
- ZVJRJPHEWFGMAX-UHFFFAOYSA-N 2-[(methylideneamino)-[1-[(3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl)methyl]imidazol-2-yl]methylidene]pent-3-enenitrile Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C(N=C)=C(C=CC)C#N ZVJRJPHEWFGMAX-UHFFFAOYSA-N 0.000 claims 1
- UUIOMTRXMKJVRQ-UHFFFAOYSA-N 2-[1-[(2-methyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]-1,3-thiazole Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CS1 UUIOMTRXMKJVRQ-UHFFFAOYSA-N 0.000 claims 1
- JCUWOVITNZXHFK-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]-1,3-thiazole Chemical compound N1=CN2N=C(C=3SC=CN=3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F JCUWOVITNZXHFK-UHFFFAOYSA-N 0.000 claims 1
- ISAAPUBECZHBGQ-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]propan-2-ol Chemical compound N1=CN2N=C(C(C)(C)O)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F ISAAPUBECZHBGQ-UHFFFAOYSA-N 0.000 claims 1
- JTXBWCRMHAVYJZ-UHFFFAOYSA-N 2-[7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]propan-2-ol Chemical compound N1=CN2N=C(C(C)(C)O)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 JTXBWCRMHAVYJZ-UHFFFAOYSA-N 0.000 claims 1
- AQQDLZIGRLPDMC-UHFFFAOYSA-N 2-chloro-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(Cl)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F AQQDLZIGRLPDMC-UHFFFAOYSA-N 0.000 claims 1
- MDMNLRIIJCLGPZ-UHFFFAOYSA-N 2-cyclobutyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C3CCC3)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 MDMNLRIIJCLGPZ-UHFFFAOYSA-N 0.000 claims 1
- LXWBGHJXKKIHGA-UHFFFAOYSA-N 2-ethoxy-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(OCC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F LXWBGHJXKKIHGA-UHFFFAOYSA-N 0.000 claims 1
- NERZUYNHTDRKCC-UHFFFAOYSA-N 2-ethyl-7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(CC)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F NERZUYNHTDRKCC-UHFFFAOYSA-N 0.000 claims 1
- SBAWYMUGSDAFIP-UHFFFAOYSA-N 2-ethyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-5-methyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=C(C)N2N=C(CC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 SBAWYMUGSDAFIP-UHFFFAOYSA-N 0.000 claims 1
- PGVWGWOXXXTRBI-UHFFFAOYSA-N 2-ethyl-7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=C(CC)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 PGVWGWOXXXTRBI-UHFFFAOYSA-N 0.000 claims 1
- MAMNCFUENSXJOF-UHFFFAOYSA-N 2-methyl-8-propyl-7-[(2-pyridin-2-ylimidazol-1-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC=N1 MAMNCFUENSXJOF-UHFFFAOYSA-N 0.000 claims 1
- LELCLASMDQWUKH-UHFFFAOYSA-N 3,8-diethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(CC)=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C LELCLASMDQWUKH-UHFFFAOYSA-N 0.000 claims 1
- PLNOLJTZHMBVMG-UHFFFAOYSA-N 3-[1-[(8-ethyl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)methyl]imidazol-2-yl]benzonitrile Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(C#N)=C1 PLNOLJTZHMBVMG-UHFFFAOYSA-N 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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| US54308304P | 2004-02-09 | 2004-02-09 | |
| PCT/US2004/023794 WO2005012306A2 (en) | 2003-07-25 | 2004-07-23 | Imidazo-pyrimidines and triazolo-pyrimidines: benzodiazepine receptor ligands |
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| JP2007500130A true JP2007500130A (ja) | 2007-01-11 |
| JP2007500130A5 JP2007500130A5 (cg-RX-API-DMAC7.html) | 2007-09-06 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008507564A (ja) * | 2004-07-24 | 2008-03-13 | エグゼリクシス， インコーポレイテッド | 核レセプターのモジュレーター |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1619948A4 (en) * | 2003-05-05 | 2007-02-14 | Neurogen Corp | SUBSTITUTED IMIDAZOLOPYRAZINE AND TRIAZOLOPYRAZINE DERIVATIVES: GABAA RECEPTOR LIGANDS |
| WO2006093911A2 (en) * | 2005-03-02 | 2006-09-08 | Neurogen Corporation | Thiazolylmethyl and oxazolylmethyl heteroaryl derivatives |
| EP1928237A4 (en) | 2005-09-02 | 2011-03-09 | Abbott Lab | NEW HETEROCYCLES BASED ON IMIDAZO |
| JP2010523716A (ja) * | 2007-04-11 | 2010-07-15 | サイプレス バイオサイエンシズ，インク． | ベンゾジアゼピン受容体拮抗薬を用いるダウン症候群の治療 |
| US8546394B2 (en) | 2007-04-17 | 2013-10-01 | Bristol-Myers Squibb Company | Substituted [1,2,4]triazolo[4,3-A]pyrazine 11-beta-hydroxysteroid dehydrogenase inhibitors |
| GB0719803D0 (en) | 2007-10-10 | 2007-11-21 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| US20090270373A1 (en) * | 2008-04-11 | 2009-10-29 | Cypress Biosciences, Inc. | Treatment of down syndrom with benzodiazepine receptor antagonists |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2000059905A1 (en) * | 1999-04-02 | 2000-10-12 | Neurogen Corporation | ARYL AND HETEROARYL FUSED AMINOALKYL-IMIDAZOLE DERIVATIVES: SELECTIVE MODULATORS OF GABAa RECEPTORS |
| WO2002074772A1 (en) * | 2001-03-21 | 2002-09-26 | Merck Sharp & Dohme Limited | Imidazo-pyrimidine derivatives as ligands for gaba receptors |
| WO2003006471A1 (en) * | 2001-07-13 | 2003-01-23 | Neurogen Corporation | Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands |
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| US544057A (en) * | 1895-08-06 | Bill and letter file | ||
| US6737242B1 (en) | 1999-05-07 | 2004-05-18 | Neurogen Corporation | Methods for screening GABA-modulatory compounds for specified pharmacological activities |
| GB9929687D0 (en) | 1999-12-15 | 2000-02-09 | Merck Sharp & Dohme | Therapeutic agents |
| US6552037B2 (en) | 2000-06-30 | 2003-04-22 | Neurogen Corporation | 2-Substituted imidazo[1,2-A]pyridine derivatives |
| GB0027561D0 (en) * | 2000-11-10 | 2000-12-27 | Merck Sharp & Dohme | Therapeutic agents |
| US6900215B2 (en) * | 2000-12-15 | 2005-05-31 | Merck Sharp & Dohme Ltd. | Imidazo-pyrimidine derivatives as ligands for gaba receptors |
| PA8535601A1 (es) * | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| US7030128B2 (en) | 2001-03-23 | 2006-04-18 | Merck Sharp & Dohme Ltd. | Imidazo-pyrimidine derivatives as ligands for GABA receptors |
| GB0128499D0 (en) * | 2001-11-28 | 2002-01-23 | Merck Sharp & Dohme | Therapeutic agents |
| US7030144B2 (en) | 2002-05-02 | 2006-04-18 | Neurogen Corporation | Substituted imidazole derivatives: GABAA receptor ligands |
| CA2484936A1 (en) | 2002-05-08 | 2004-05-21 | Neurogen Corporation | Substituted imidazolylmethyl pyridine and pyrazine derivatives and their use as gabaa receptor ligands |
| JP2006502974A (ja) | 2002-05-17 | 2006-01-26 | ニューロジェン コーポレイション | 置換環縮合イミダゾール誘導体：ｇａｂａａ受容体リガンド |
| CN100579579C (zh) | 2002-10-01 | 2010-01-13 | 诺华疫苗和诊断公司 | 抗癌及抗感染性疾病组合物及其使用方法 |
| DE60307499T2 (de) | 2002-11-08 | 2007-02-01 | Neurogen Corp., Branford | 4-imidazol-1-ylmethylpyrimidinderivate als liganden für gabaa-rezeptoren |
| EP1619948A4 (en) | 2003-05-05 | 2007-02-14 | Neurogen Corp | SUBSTITUTED IMIDAZOLOPYRAZINE AND TRIAZOLOPYRAZINE DERIVATIVES: GABAA RECEPTOR LIGANDS |
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- 2004-07-23 DK DK04779031T patent/DK1648899T3/da active
- 2004-07-23 WO PCT/US2004/023794 patent/WO2005012306A2/en not_active Ceased
- 2004-07-23 PT PT04779031T patent/PT1648899E/pt unknown
- 2004-07-23 US US10/898,690 patent/US7271170B2/en not_active Expired - Lifetime
- 2004-07-23 ES ES04779031T patent/ES2278345T3/es not_active Expired - Lifetime
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- 2004-07-23 DE DE602004004143T patent/DE602004004143T2/de not_active Expired - Lifetime
- 2004-07-23 CA CA002537331A patent/CA2537331A1/en not_active Abandoned
- 2004-07-23 PL PL04779031T patent/PL1648899T3/pl unknown
- 2004-07-23 EP EP04779031A patent/EP1648899B1/en not_active Expired - Lifetime
- 2004-07-23 JP JP2006521278A patent/JP2007500130A/ja active Pending
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- 2004-07-26 TW TW093122247A patent/TW200524937A/zh unknown
- 2004-07-26 AR ARP040102649A patent/AR045117A1/es unknown
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- 2006-01-19 IL IL173265A patent/IL173265A0/en unknown
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- 2007-02-26 CY CY20071100262T patent/CY1107565T1/el unknown
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000059905A1 (en) * | 1999-04-02 | 2000-10-12 | Neurogen Corporation | ARYL AND HETEROARYL FUSED AMINOALKYL-IMIDAZOLE DERIVATIVES: SELECTIVE MODULATORS OF GABAa RECEPTORS |
| WO2002074772A1 (en) * | 2001-03-21 | 2002-09-26 | Merck Sharp & Dohme Limited | Imidazo-pyrimidine derivatives as ligands for gaba receptors |
| WO2003006471A1 (en) * | 2001-07-13 | 2003-01-23 | Neurogen Corporation | Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008507564A (ja) * | 2004-07-24 | 2008-03-13 | エグゼリクシス， インコーポレイテッド | 核レセプターのモジュレーター |
Also Published As
| Publication number | Publication date |
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| US20050038043A1 (en) | 2005-02-17 |
| KR20060098425A (ko) | 2006-09-18 |
| NZ544262A (en) | 2009-06-26 |
| US7271170B2 (en) | 2007-09-18 |
| DE602004004143T2 (de) | 2007-10-11 |
| BRPI0412908A (pt) | 2006-09-26 |
| WO2005012306A3 (en) | 2005-04-14 |
| MXPA06000887A (es) | 2006-04-19 |
| PL1648899T3 (pl) | 2007-06-29 |
| TW200524937A (en) | 2005-08-01 |
| HK1089446A1 (en) | 2006-12-01 |
| EP1648899B1 (en) | 2007-01-03 |
| DK1648899T3 (da) | 2007-04-02 |
| US20080139580A1 (en) | 2008-06-12 |
| ES2278345T3 (es) | 2007-08-01 |
| DE602004004143D1 (de) | 2007-02-15 |
| WO2005012306A2 (en) | 2005-02-10 |
| ATE350382T1 (de) | 2007-01-15 |
| IL173265A0 (en) | 2006-06-11 |
| CA2537331A1 (en) | 2005-02-10 |
| PT1648899E (pt) | 2007-03-30 |
| CY1107565T1 (el) | 2013-03-13 |
| AR045117A1 (es) | 2005-10-19 |
| AU2004261591A1 (en) | 2005-02-10 |
| EP1648899A2 (en) | 2006-04-26 |
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