KR20060098425A - 이미다조-피리미딘 및 트리아졸로-피리미딘: 벤조디아제핀수용체 리간드 - Google Patents
이미다조-피리미딘 및 트리아졸로-피리미딘: 벤조디아제핀수용체 리간드 Download PDFInfo
- Publication number
- KR20060098425A KR20060098425A KR1020067001782A KR20067001782A KR20060098425A KR 20060098425 A KR20060098425 A KR 20060098425A KR 1020067001782 A KR1020067001782 A KR 1020067001782A KR 20067001782 A KR20067001782 A KR 20067001782A KR 20060098425 A KR20060098425 A KR 20060098425A
- Authority
- KR
- South Korea
- Prior art keywords
- imidazol
- triazolo
- pyrimidine
- propyl
- ylmethyl
- 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.)
- Ceased
Links
- 239000003446 ligand Substances 0.000 title abstract description 16
- 150000005237 imidazopyrimidines Chemical class 0.000 title description 4
- 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 330
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 159
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 158
- 238000000034 method Methods 0.000 claims abstract description 60
- 230000000694 effects Effects 0.000 claims abstract description 41
- 230000027455 binding Effects 0.000 claims abstract description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- -1 nitro, cyano, amino Chemical group 0.000 claims description 221
- 102000005962 receptors Human genes 0.000 claims description 156
- 108020003175 receptors Proteins 0.000 claims description 156
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 229910052736 halogen Inorganic materials 0.000 claims description 63
- 150000002367 halogens Chemical class 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 56
- 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 51
- 150000003839 salts Chemical class 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 239000000523 sample Substances 0.000 claims description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 238000012360 testing method Methods 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 208000019901 Anxiety disease Diseases 0.000 claims description 23
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 23
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 23
- 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 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 230000036506 anxiety Effects 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000005518 carboxamido group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 208000019116 sleep disease Diseases 0.000 claims description 17
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 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
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 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
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- 238000005259 measurement Methods 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 208000000044 Amnesia Diseases 0.000 claims description 8
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 8
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 8
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000006403 short-term memory Effects 0.000 claims description 8
- 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 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
- 238000005406 washing Methods 0.000 claims description 7
- 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 6
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 238000000376 autoradiography Methods 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 238000006467 substitution reaction 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
- 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 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 230000007831 electrophysiology Effects 0.000 claims description 5
- 238000002001 electrophysiology Methods 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 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 4
- 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 4
- DNRXICIPOQCKBX-UHFFFAOYSA-N 7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F DNRXICIPOQCKBX-UHFFFAOYSA-N 0.000 claims description 4
- AFVWKPXVQGAVPE-UHFFFAOYSA-N 7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propylimidazo[1,2-c]pyrimidine Chemical compound N1=CN2C=CN=C2C(CCC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 AFVWKPXVQGAVPE-UHFFFAOYSA-N 0.000 claims description 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
- 150000005215 alkyl ethers Chemical class 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
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 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
- 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 3
- 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 3
- 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 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
- 239000002775 capsule Substances 0.000 claims description 3
- 239000013068 control sample Substances 0.000 claims description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 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
- 125000002861 (C1-C4) alkanoyl 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
- 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 description 2
- ZYNLZENDPKIIDI-UHFFFAOYSA-N 7-[[2-(2-chlorophenyl)imidazol-1-yl]methyl]-8-ethyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC=C1Cl ZYNLZENDPKIIDI-UHFFFAOYSA-N 0.000 claims description 2
- VZJOLTPAOSKMGJ-UHFFFAOYSA-N 7-[[2-(5-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=CC=C(F)C=N1 VZJOLTPAOSKMGJ-UHFFFAOYSA-N 0.000 claims description 2
- JWGDOTNRVDLEMB-UHFFFAOYSA-N 7-[[2-(6-chloropyridin-2-yl)imidazol-1-yl]methyl]-8-ethyl-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(Cl)=N1 JWGDOTNRVDLEMB-UHFFFAOYSA-N 0.000 claims description 2
- WROXUUQTMWXOED-UHFFFAOYSA-N 8-ethyl-7-[[2-(3-fluorophenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC=CC(F)=C1 WROXUUQTMWXOED-UHFFFAOYSA-N 0.000 claims description 2
- ITHWHVPDFQHQKS-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methoxyphenyl)imidazol-1-yl]methyl]-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=CN2N=CN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1OC ITHWHVPDFQHQKS-UHFFFAOYSA-N 0.000 claims description 2
- CPFQCLXQWTYQOL-UHFFFAOYSA-N 8-ethyl-7-[[2-(5-fluoro-2-methylphenyl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidine Chemical compound N1=CN2C(C)=NN=C2C(CC)=C1CN1C=CN=C1C1=CC(F)=CC=C1C CPFQCLXQWTYQOL-UHFFFAOYSA-N 0.000 claims description 2
- 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 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
- UAMAIHOEGLEXSV-UHFFFAOYSA-N adipiplon Chemical compound N1=CN2N=C(C)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F UAMAIHOEGLEXSV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000005843 halogen group Chemical group 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
- 238000012546 transfer Methods 0.000 claims description 2
- NUJDBYIZEFSXJP-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2N=C(C)N=C2C(C(O)CC)=C1CN1C=CN=C1C1=NC=CC=C1F NUJDBYIZEFSXJP-UHFFFAOYSA-N 0.000 claims 1
- MEHYNRSHIWOOMA-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2C(C)=NN=C2C(C(O)CC)=C1CN1C=CN=C1C1=NC=CC=C1F MEHYNRSHIWOOMA-UHFFFAOYSA-N 0.000 claims 1
- KDHJNMHGCNOHTL-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl]ethanol Chemical compound N1=CN2N=C(C(C)O)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F KDHJNMHGCNOHTL-UHFFFAOYSA-N 0.000 claims 1
- ABHZXJAGIJWWEE-UHFFFAOYSA-N 1-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-yl]ethanol Chemical compound N1=CN2C(C(C)O)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F ABHZXJAGIJWWEE-UHFFFAOYSA-N 0.000 claims 1
- CQIVCBJKDYNCEP-UHFFFAOYSA-N 1-[7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2N=C(C)N=C2C(C(O)CC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 CQIVCBJKDYNCEP-UHFFFAOYSA-N 0.000 claims 1
- IYGGACKRMNWBSI-UHFFFAOYSA-N 1-[7-[[2-(6-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]propan-1-ol Chemical compound N1=CN2C(C)=NN=C2C(C(O)CC)=C1CN1C=CN=C1C1=CC=CC(F)=N1 IYGGACKRMNWBSI-UHFFFAOYSA-N 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
- GOPZZXGUDALQEB-UHFFFAOYSA-N 2-(cyclopentyloxymethyl)-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(COC3CCCC3)N=C2C(CCC)=C1CN1C=CN=C1C1=NC=CC=C1F GOPZZXGUDALQEB-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
- 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
- CQGORZBTKUXQKD-UHFFFAOYSA-N 2-[1-[(3-methyl-8-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl)methyl]imidazol-2-yl]-1,3-thiazole Chemical compound N1=CN2C(C)=NN=C2C(CCC)=C1CN1C=CN=C1C1=NC=CS1 CQGORZBTKUXQKD-UHFFFAOYSA-N 0.000 claims 1
- DXFPPOJKGNNLKF-UHFFFAOYSA-N 2-[1-[[8-(3-fluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl]methyl]imidazol-2-yl]pyridine-3-carbonitrile Chemical compound N1=CN2C=NN=C2C(CCCF)=C1CN1C=CN=C1C1=NC=CC=C1C#N DXFPPOJKGNNLKF-UHFFFAOYSA-N 0.000 claims 1
- ZFHXYIHQAPCFBD-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-2-methyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]ethanol Chemical compound N1=CN2N=C(C)N=C2C(CCO)=C1CN1C=CN=C1C1=NC=CC=C1F ZFHXYIHQAPCFBD-UHFFFAOYSA-N 0.000 claims 1
- RVXISMXQFQNUMO-UHFFFAOYSA-N 2-[7-[[2-(3-fluoropyridin-2-yl)imidazol-1-yl]methyl]-3-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]ethanol Chemical compound N1=CN2C(C)=NN=C2C(CCO)=C1CN1C=CN=C1C1=NC=CC=C1F RVXISMXQFQNUMO-UHFFFAOYSA-N 0.000 claims 1
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- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
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- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| US49000603P | 2003-07-25 | 2003-07-25 | |
| US60/490,006 | 2003-07-25 | ||
| US54308304P | 2004-02-09 | 2004-02-09 | |
| US60/543,083 | 2004-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060098425A true KR20060098425A (ko) | 2006-09-18 |
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| KR1020067001782A Ceased KR20060098425A (ko) | 2003-07-25 | 2004-07-23 | 이미다조-피리미딘 및 트리아졸로-피리미딘: 벤조디아제핀수용체 리간드 |
Country Status (20)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7482366B2 (en) * | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| 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 |
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| US544057A (en) * | 1895-08-06 | Bill and letter file | ||
| DE60014339T8 (de) * | 1999-04-02 | 2006-04-27 | Neurogen Corp., Branford | Aryl- und heteroaryl-kondensierte aminoalkyl-imidazol-derivate: selektive modulatoren der gabaa-rezeptoren |
| 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 |
| TWI248936B (en) * | 2001-03-21 | 2006-02-11 | Merck Sharp & Dohme | Imidazo-pyrimidine derivatives as ligands for GABA receptors |
| US7030128B2 (en) | 2001-03-23 | 2006-04-18 | Merck Sharp & Dohme Ltd. | Imidazo-pyrimidine derivatives as ligands for GABA receptors |
| IL159811A0 (en) | 2001-07-13 | 2004-06-20 | Neurogen Corp | Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands |
| 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 |
-
2004
- 2004-07-23 AT AT04779031T patent/ATE350382T1/de not_active IP Right Cessation
- 2004-07-23 MX MXPA06000887A patent/MXPA06000887A/es active IP Right Grant
- 2004-07-23 AU AU2004261591A patent/AU2004261591A1/en not_active Abandoned
- 2004-07-23 BR BRPI0412908-3A patent/BRPI0412908A/pt not_active IP Right Cessation
- 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
- 2004-07-23 KR KR1020067001782A patent/KR20060098425A/ko not_active Ceased
- 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
- 2004-07-23 NZ NZ544262A patent/NZ544262A/xx unknown
- 2004-07-26 TW TW093122247A patent/TW200524937A/zh unknown
- 2004-07-26 AR ARP040102649A patent/AR045117A1/es unknown
-
2006
- 2006-01-19 IL IL173265A patent/IL173265A0/en unknown
-
2007
- 2007-02-26 CY CY20071100262T patent/CY1107565T1/el unknown
- 2007-09-14 US US11/855,386 patent/US20080139580A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20050038043A1 (en) | 2005-02-17 |
| 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 |
| JP2007500130A (ja) | 2007-01-11 |
| 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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