ES2494846T3 - Derivados de pirazol como moduladores del receptor de la serotonina 5-HT2A útiles para el tratamiento de los trastornos relacionados con el mismo - Google Patents
Derivados de pirazol como moduladores del receptor de la serotonina 5-HT2A útiles para el tratamiento de los trastornos relacionados con el mismo Download PDFInfo
- Publication number
- ES2494846T3 ES2494846T3 ES07839161.2T ES07839161T ES2494846T3 ES 2494846 T3 ES2494846 T3 ES 2494846T3 ES 07839161 T ES07839161 T ES 07839161T ES 2494846 T3 ES2494846 T3 ES 2494846T3
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- ES
- Spain
- Prior art keywords
- pyrazol
- piperazin
- methyl
- phenyl
- fluoro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000011282 treatment Methods 0.000 title claims description 110
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 65
- 208000035475 disorder Diseases 0.000 title claims description 43
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 title description 40
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 title description 32
- 150000003217 pyrazoles Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 395
- -1 (4- (1 H -pyrazol-3-carbonyl) piperazin-1-yl) -2- (4-fluoro-1H-indole-3-yl) ethane Chemical compound 0.000 claims abstract description 162
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 68
- 125000003118 aryl group Chemical group 0.000 claims abstract description 40
- 125000001424 substituent group Chemical group 0.000 claims abstract description 39
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 35
- 150000002367 halogens Chemical class 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 23
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 22
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 19
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 19
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000006823 (C1-C6) acyl group Chemical group 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 11
- 150000004677 hydrates Chemical class 0.000 claims abstract description 11
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims abstract description 10
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims abstract description 9
- 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 claims abstract description 9
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims abstract description 9
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims abstract description 8
- ABDMQSFNJPYOLA-UHFFFAOYSA-N NS(=O)(=O)[N+]([O-])=O Chemical compound NS(=O)(=O)[N+]([O-])=O ABDMQSFNJPYOLA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000005363 dialkylsulfonamide group Chemical group 0.000 claims abstract description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 6
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 6
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims abstract description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 5
- 125000004995 haloalkylthio group Chemical group 0.000 claims abstract description 5
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 4
- HIUCEDHORNFIDK-UHFFFAOYSA-N [O-][N+](=O)S(=O)(=O)N=O Chemical compound [O-][N+](=O)S(=O)(=O)N=O HIUCEDHORNFIDK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 claims abstract 8
- 230000007958 sleep Effects 0.000 claims description 150
- 239000000203 mixture Substances 0.000 claims description 72
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 claims description 47
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 claims description 46
- 239000003814 drug Substances 0.000 claims description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims description 39
- 241000282414 Homo sapiens Species 0.000 claims description 35
- 208000019116 sleep disease Diseases 0.000 claims description 34
- 241001465754 Metazoa Species 0.000 claims description 32
- 238000004519 manufacturing process Methods 0.000 claims description 28
- 201000000980 schizophrenia Diseases 0.000 claims description 22
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 206010022437 insomnia Diseases 0.000 claims description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 15
- 208000006011 Stroke Diseases 0.000 claims description 15
- 208000020685 sleep-wake disease Diseases 0.000 claims description 15
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 15
- 230000001965 increasing effect Effects 0.000 claims description 14
- 150000003857 carboxamides Chemical class 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 13
- 208000010125 myocardial infarction Diseases 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 11
- 238000007596 consolidation process Methods 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 230000036407 pain Effects 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
- 206010002383 Angina Pectoris Diseases 0.000 claims description 10
- 230000035602 clotting Effects 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 claims description 9
- 239000000442 dopamine 2 receptor blocking agent Substances 0.000 claims description 9
- 238000012423 maintenance Methods 0.000 claims description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 208000029078 coronary artery disease Diseases 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- VYLNMUMHHZDSFF-UHFFFAOYSA-N 2-[4-(1,5-dimethylpyrazole-3-carbonyl)piperazin-1-yl]-1-(4-fluorophenyl)ethanone Chemical compound CN1C(C)=CC(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 VYLNMUMHHZDSFF-UHFFFAOYSA-N 0.000 claims description 6
- WHQBXIJBXXREON-UHFFFAOYSA-N 2-[4-(4-bromo-1-methylpyrazole-3-carbonyl)piperazin-1-yl]-1-(4-fluorophenyl)ethanone Chemical compound CN1C=C(Br)C(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 WHQBXIJBXXREON-UHFFFAOYSA-N 0.000 claims description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 208000006199 Parasomnias Diseases 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- KSDRDHTWNXOAEK-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(5-methyl-1h-pyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound N1C(C)=CC(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 KSDRDHTWNXOAEK-UHFFFAOYSA-N 0.000 claims description 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- AIIXEXZEELKXDV-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(2,4-difluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Br)C(C(=O)N2CCN(CCC=3C(=CC(F)=CC=3)F)CC2)=N1 AIIXEXZEELKXDV-UHFFFAOYSA-N 0.000 claims description 4
- AWERQXNYLVECDD-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(4-iodo-1-methylpyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound CN1C=C(I)C(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 AWERQXNYLVECDD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- BGSXCNQHFNNWSV-UHFFFAOYSA-N 2-[4-(4-chloro-1-ethylpyrazole-3-carbonyl)piperazin-1-yl]-1-(4-fluorophenyl)ethanone Chemical compound CCN1C=C(Cl)C(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 BGSXCNQHFNNWSV-UHFFFAOYSA-N 0.000 claims description 4
- QUDDUNFBOHGRTM-UHFFFAOYSA-N 2-[4-(4-chloro-1-methylpyrazole-3-carbonyl)piperazin-1-yl]-1-(4-fluorophenyl)ethanone Chemical compound CN1C=C(Cl)C(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 QUDDUNFBOHGRTM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
- CENVPIZOTHULGJ-UHFFFAOYSA-N 6-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C2CC(=O)NC2=C1 CENVPIZOTHULGJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000739 antihistaminic agent Substances 0.000 claims description 4
- DSNAKELDWHINON-UHFFFAOYSA-N (1,5-dimethylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C(C)=CC(C(=O)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 DSNAKELDWHINON-UHFFFAOYSA-N 0.000 claims description 3
- BESZVTQDWDEIIE-CYBMUJFWSA-N (4-bromo-1,5-dimethylpyrazol-3-yl)-[(3r)-4-[2-(4-fluorophenyl)ethyl]-3-methylpiperazin-1-yl]methanone Chemical compound C([C@H]1C)N(C(=O)C=2C(=C(C)N(C)N=2)Br)CCN1CCC1=CC=C(F)C=C1 BESZVTQDWDEIIE-CYBMUJFWSA-N 0.000 claims description 3
- BESZVTQDWDEIIE-ZDUSSCGKSA-N (4-bromo-1,5-dimethylpyrazol-3-yl)-[(3s)-4-[2-(4-fluorophenyl)ethyl]-3-methylpiperazin-1-yl]methanone Chemical compound C([C@@H]1C)N(C(=O)C=2C(=C(C)N(C)N=2)Br)CCN1CCC1=CC=C(F)C=C1 BESZVTQDWDEIIE-ZDUSSCGKSA-N 0.000 claims description 3
- JXSSWYOGHJSFPO-UHFFFAOYSA-N (4-bromo-1,5-dimethylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C(C)=C(Br)C(C(=O)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 JXSSWYOGHJSFPO-UHFFFAOYSA-N 0.000 claims description 3
- WVZBBNMCBUYOBY-ZDUSSCGKSA-N (4-bromo-1-methylpyrazol-3-yl)-[(2s)-4-[2-(4-fluorophenyl)ethyl]-2-methylpiperazin-1-yl]methanone Chemical compound C([C@@H](N(CC1)C(=O)C=2C(=CN(C)N=2)Br)C)N1CCC1=CC=C(F)C=C1 WVZBBNMCBUYOBY-ZDUSSCGKSA-N 0.000 claims description 3
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- ZHNOCIYPSZCKLU-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(3-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Br)C(C(=O)N2CCN(CCC=3C=C(Cl)C=CC=3)CC2)=N1 ZHNOCIYPSZCKLU-UHFFFAOYSA-N 0.000 claims description 3
- MMCDYTKWOGXBIZ-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(3-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Br)C(C(=O)N2CCN(CCC=3C=C(F)C=CC=3)CC2)=N1 MMCDYTKWOGXBIZ-UHFFFAOYSA-N 0.000 claims description 3
- JNDVWGDRNWQCLW-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Br)C(C(=O)N2CCN(CC(O)C=3C=CC(F)=CC=3)CC2)=N1 JNDVWGDRNWQCLW-UHFFFAOYSA-N 0.000 claims description 3
- FDUKUFJFCLLMNB-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)-2-methoxyiminoethyl]piperazin-1-yl]methanone Chemical compound C=1C=C(F)C=CC=1C(=NOC)CN(CC1)CCN1C(=O)C1=NN(C)C=C1Br FDUKUFJFCLLMNB-UHFFFAOYSA-N 0.000 claims description 3
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- HGDAGLUEBPHHHL-UHFFFAOYSA-N (4-bromo-1-methylpyrazol-3-yl)-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C(=O)C=2C(=CN(C)N=2)Br)CC1 HGDAGLUEBPHHHL-UHFFFAOYSA-N 0.000 claims description 3
- QLXDKNJBLKLFNW-UHFFFAOYSA-N (4-bromo-2-methylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1N=CC(Br)=C1C(=O)N1CCN(CCC=2C=CC(F)=CC=2)CC1 QLXDKNJBLKLFNW-UHFFFAOYSA-N 0.000 claims description 3
- COACYZUGEQXHHO-UHFFFAOYSA-N (4-chloro-1,5-dimethylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C(C)=C(Cl)C(C(=O)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 COACYZUGEQXHHO-UHFFFAOYSA-N 0.000 claims description 3
- QRMOURVKIBQGRP-UHFFFAOYSA-N (4-chloro-1-ethylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CCN1C=C(Cl)C(C(=O)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 QRMOURVKIBQGRP-UHFFFAOYSA-N 0.000 claims description 3
- RTGHHABZYVOEPJ-UHFFFAOYSA-N (4-chloro-1-methylpyrazol-3-yl)-[4-[2-(2,4-difluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Cl)C(C(=O)N2CCN(CCC=3C(=CC(F)=CC=3)F)CC2)=N1 RTGHHABZYVOEPJ-UHFFFAOYSA-N 0.000 claims description 3
- UTEDKNZKMRUJFJ-UHFFFAOYSA-N (4-chloro-1-methylpyrazol-3-yl)-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Cl)C(C(=O)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=N1 UTEDKNZKMRUJFJ-UHFFFAOYSA-N 0.000 claims description 3
- OFUYCOGAWAJNBT-UHFFFAOYSA-N (4-chloro-1-methylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)-2-methylpropyl]piperazin-1-yl]methanone Chemical compound CN1C=C(Cl)C(C(=O)N2CCN(CC(C)(C)C=3C=CC(F)=CC=3)CC2)=N1 OFUYCOGAWAJNBT-UHFFFAOYSA-N 0.000 claims description 3
- UQKJQWRXESSEAT-UHFFFAOYSA-N (4-chloro-1-methylpyrazol-3-yl)-[4-[2-(4-fluorophenyl)propyl]piperazin-1-yl]methanone Chemical compound C=1C=C(F)C=CC=1C(C)CN(CC1)CCN1C(=O)C1=NN(C)C=C1Cl UQKJQWRXESSEAT-UHFFFAOYSA-N 0.000 claims description 3
- SLOVWNRKQOAIHG-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound C1=CC(F)=CC=C1C(=O)CN1CCN(C(=O)C=2C=3CCCC=3NN=2)CC1 SLOVWNRKQOAIHG-UHFFFAOYSA-N 0.000 claims description 3
- XVRWPMHKTPWPBY-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(1-methyl-5-phenylpyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound CN1N=C(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)C=C1C1=CC=CC=C1 XVRWPMHKTPWPBY-UHFFFAOYSA-N 0.000 claims description 3
- SGCIVAJSWROLHV-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(1-methylpyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound CN1C=CC(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 SGCIVAJSWROLHV-UHFFFAOYSA-N 0.000 claims description 3
- LNFOMKZHVYNUGT-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(2-methyl-5-phenylpyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound CN1N=C(C=2C=CC=CC=2)C=C1C(=O)N(CC1)CCN1CC(=O)C1=CC=C(F)C=C1 LNFOMKZHVYNUGT-UHFFFAOYSA-N 0.000 claims description 3
- VCMPTUVNTZZCQN-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(3-nitro-1h-pyrazole-5-carbonyl)piperazin-1-yl]ethanone Chemical compound N1C([N+](=O)[O-])=CC(C(=O)N2CCN(CC(=O)C=3C=CC(F)=CC=3)CC2)=N1 VCMPTUVNTZZCQN-UHFFFAOYSA-N 0.000 claims description 3
- QSORPHUIDRVFFD-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-[4-(5-propan-2-yl-1h-pyrazole-3-carbonyl)piperazin-1-yl]ethanone Chemical compound N1N=C(C(C)C)C=C1C(=O)N1CCN(CC(=O)C=2C=CC(F)=CC=2)CC1 QSORPHUIDRVFFD-UHFFFAOYSA-N 0.000 claims description 3
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- C07—ORGANIC CHEMISTRY
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Landscapes
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| US84907006P | 2006-10-03 | 2006-10-03 | |
| US849070P | 2006-10-03 | ||
| PCT/US2007/021182 WO2008042388A1 (en) | 2006-10-03 | 2007-10-02 | Pyrazole derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
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| ES2494846T3 true ES2494846T3 (es) | 2014-09-16 |
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| JP4198733B2 (ja) * | 2003-07-22 | 2008-12-17 | アリーナ ファーマシューティカルズ， インコーポレイテッド | 関連性障害の予防および処置に有用な、５−ｈｔ２ａセロトニンレセプターのモジュレーターとしてのジアリールおよびアリールへテロアリールウレア誘導体 |
| SA05260357B1 (ar) | 2004-11-19 | 2008-09-08 | ارينا فارماسيتو تيكالز ، أنك | مشتقات 3_فينيل_بيرازول كمعدلات لمستقبل سيروتينين 5_ht2a مفيدة في علاج الاضطرابات المتعلقه به |
| AU2007254244C1 (en) | 2006-05-18 | 2014-07-31 | Arena Pharmaceuticals, Inc. | 3-pyrazolyl-benzamide-4-ethers, secondary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto |
| JP5406018B2 (ja) | 2006-05-18 | 2014-02-05 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ５−ｈｔ２ａセロトニンレセプターに関連する障害の処置に有用な５−ｈｔ２ａセロトニンレセプターのモジュレーターとしての１級アミン、およびその誘導体 |
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-
2007
- 2007-09-28 TW TW096136466A patent/TWI415845B/zh not_active IP Right Cessation
- 2007-10-02 CN CN201210300858.0A patent/CN102838546B/zh not_active Expired - Fee Related
- 2007-10-02 AU AU2007305235A patent/AU2007305235C1/en not_active Ceased
- 2007-10-02 CN CN2007800371033A patent/CN101611013B/zh not_active Expired - Fee Related
- 2007-10-02 WO PCT/US2007/021182 patent/WO2008042388A1/en not_active Ceased
- 2007-10-02 AR ARP070104362A patent/AR063100A1/es active IP Right Grant
- 2007-10-02 JP JP2009531423A patent/JP5346292B2/ja not_active Expired - Fee Related
- 2007-10-02 CA CA2664398A patent/CA2664398C/en active Active
- 2007-10-02 EP EP07839161.2A patent/EP2066641B1/en active Active
- 2007-10-02 ES ES07839161.2T patent/ES2494846T3/es active Active
- 2007-10-02 US US12/444,098 patent/US9434692B2/en active Active
- 2007-10-03 PE PE2007001335A patent/PE20081454A1/es active IP Right Grant
- 2007-10-03 PA PA20078749401A patent/PA8749401A1/es unknown
- 2007-10-03 CL CL200702859A patent/CL2007002859A1/es unknown
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2012
- 2012-09-13 US US13/614,537 patent/US20130217700A1/en not_active Abandoned
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- 2013-07-05 JP JP2013141517A patent/JP2013199493A/ja not_active Withdrawn
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2015
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- 2017-07-24 US US15/657,896 patent/US10351531B2/en active Active
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2019
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Also Published As
| Publication number | Publication date |
|---|---|
| TWI415845B (zh) | 2013-11-21 |
| TW200823201A (en) | 2008-06-01 |
| US9732039B2 (en) | 2017-08-15 |
| AU2007305235A1 (en) | 2008-04-10 |
| AU2007305235C1 (en) | 2012-12-13 |
| US9434692B2 (en) | 2016-09-06 |
| PE20081454A1 (es) | 2008-10-18 |
| CN102838546A (zh) | 2012-12-26 |
| US20100004264A1 (en) | 2010-01-07 |
| CL2007002859A1 (es) | 2008-06-06 |
| PA8749401A1 (es) | 2009-02-09 |
| CA2664398A1 (en) | 2008-04-10 |
| US20130217700A1 (en) | 2013-08-22 |
| JP2010505832A (ja) | 2010-02-25 |
| AR063100A1 (es) | 2008-12-30 |
| CN102838546B (zh) | 2015-07-15 |
| CN101611013A (zh) | 2009-12-23 |
| JO2954B1 (en) | 2016-03-15 |
| US10351531B2 (en) | 2019-07-16 |
| US20200048205A1 (en) | 2020-02-13 |
| CN101611013B (zh) | 2012-09-05 |
| JP2013199493A (ja) | 2013-10-03 |
| US20170320831A1 (en) | 2017-11-09 |
| US20210380537A1 (en) | 2021-12-09 |
| EP2066641A1 (en) | 2009-06-10 |
| WO2008042388A1 (en) | 2008-04-10 |
| JP5346292B2 (ja) | 2013-11-20 |
| AU2007305235B2 (en) | 2012-05-17 |
| EP2066641B1 (en) | 2014-06-04 |
| US20160075660A1 (en) | 2016-03-17 |
| CA2664398C (en) | 2018-03-13 |
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