EP1242080A1 - Inhibitoren von dopaminetransport und deren verwendung - Google Patents
Inhibitoren von dopaminetransport und deren verwendungInfo
- Publication number
- EP1242080A1 EP1242080A1 EP00968417A EP00968417A EP1242080A1 EP 1242080 A1 EP1242080 A1 EP 1242080A1 EP 00968417 A EP00968417 A EP 00968417A EP 00968417 A EP00968417 A EP 00968417A EP 1242080 A1 EP1242080 A1 EP 1242080A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- hydroxy
- methyl
- dichlorophenyl
- aryl
- 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.)
- Withdrawn
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 24
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 title abstract description 15
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 title abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 342
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 303
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 164
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 138
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 67
- 238000011282 treatment Methods 0.000 claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000002576 ketones Chemical class 0.000 claims abstract description 10
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 305
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 183
- 229960003920 cocaine Drugs 0.000 claims description 152
- 125000001424 substituent group Chemical group 0.000 claims description 128
- 229910052731 fluorine Inorganic materials 0.000 claims description 118
- 125000003545 alkoxy group Chemical group 0.000 claims description 108
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 108
- 125000004122 cyclic group Chemical group 0.000 claims description 102
- 125000003277 amino group Chemical group 0.000 claims description 99
- 229960003638 dopamine Drugs 0.000 claims description 90
- 229910052757 nitrogen Inorganic materials 0.000 claims description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims description 64
- 229910052760 oxygen Inorganic materials 0.000 claims description 53
- 229910052717 sulfur Inorganic materials 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 47
- 230000005764 inhibitory process Effects 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 20
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 20
- -1 3,4-difluorophenyl Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- NQHSMRHMUBKGPZ-UHFFFAOYSA-N (3,4-dichlorophenyl)-[4-(3,4-dichlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=C(Cl)C(Cl)=CC=2)C1C(=O)C1=CC=C(Cl)C(Cl)=C1 NQHSMRHMUBKGPZ-UHFFFAOYSA-N 0.000 claims description 13
- 208000022497 Cocaine-Related disease Diseases 0.000 claims description 13
- XJLDYKIEURAVBW-UHFFFAOYSA-N 3-decanone Chemical compound CCCCCCCC(=O)CC XJLDYKIEURAVBW-UHFFFAOYSA-N 0.000 claims description 12
- 206010013654 Drug abuse Diseases 0.000 claims description 11
- 201000001272 cocaine abuse Diseases 0.000 claims description 11
- XEUXCKGGBTVKCX-UHFFFAOYSA-N 2-chloro-1-(4-chloro-3-methylphenyl)ethanone Chemical compound CC1=CC(C(=O)CCl)=CC=C1Cl XEUXCKGGBTVKCX-UHFFFAOYSA-N 0.000 claims description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
- XBUDQFASFMZZTM-UHFFFAOYSA-N (4-chloro-3-methylphenyl)-[4-(4-chloro-3-methylphenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=C(C)C(Cl)=CC=2)C1C(=O)C1=CC=C(Cl)C(C)=C1 XBUDQFASFMZZTM-UHFFFAOYSA-N 0.000 claims description 9
- XOIGZLJCLDWTQH-UHFFFAOYSA-N 1-(4-chloro-3-methylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C(C)=C1 XOIGZLJCLDWTQH-UHFFFAOYSA-N 0.000 claims description 9
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
- PUSUWOVAIYTHGX-UHFFFAOYSA-N (2-chlorophenyl)-[4-(2-chlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C(=CC=CC=2)Cl)C1C(=O)C1=CC=CC=C1Cl PUSUWOVAIYTHGX-UHFFFAOYSA-N 0.000 claims description 8
- OJDYOYOACQNEAI-UHFFFAOYSA-N (3,4-dichlorophenyl)-[4-(3,4-dichlorophenyl)-1-ethyl-4-hydroxypiperidin-3-yl]methanone Chemical compound C1N(CC)CCC(O)(C=2C=C(Cl)C(Cl)=CC=2)C1C(=O)C1=CC=C(Cl)C(Cl)=C1 OJDYOYOACQNEAI-UHFFFAOYSA-N 0.000 claims description 8
- HBDWQJUIOVZBNJ-UHFFFAOYSA-N (3,4-dichlorophenyl)-[4-(3,4-dichlorophenyl)-4-hydroxy-1-(2-phenylethyl)piperidin-3-yl]methanone Chemical compound C1C(C(=O)C=2C=C(Cl)C(Cl)=CC=2)C(O)(C=2C=C(Cl)C(Cl)=CC=2)CCN1CCC1=CC=CC=C1 HBDWQJUIOVZBNJ-UHFFFAOYSA-N 0.000 claims description 8
- ZYLGUERFZHZIQJ-UHFFFAOYSA-N (3-chlorophenyl)-[4-(3-chlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=C(Cl)C=CC=2)C1C(=O)C1=CC=CC(Cl)=C1 ZYLGUERFZHZIQJ-UHFFFAOYSA-N 0.000 claims description 8
- ULBYPYALIPCMAF-UHFFFAOYSA-N (4-bromophenyl)-[4-(4-bromophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=CC(Br)=CC=2)C1C(=O)C1=CC=C(Br)C=C1 ULBYPYALIPCMAF-UHFFFAOYSA-N 0.000 claims description 8
- LFQIXZHWOHBULT-UHFFFAOYSA-N (4-chlorophenyl)-[4-(4-chlorophenyl)-1-ethyl-4-hydroxypiperidin-3-yl]methanone Chemical compound C1N(CC)CCC(O)(C=2C=CC(Cl)=CC=2)C1C(=O)C1=CC=C(Cl)C=C1 LFQIXZHWOHBULT-UHFFFAOYSA-N 0.000 claims description 8
- OVHJBARWJMLZJX-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-3-[(2,4-dichlorophenyl)-hydroxymethyl]-1-methylpiperidin-4-ol Chemical compound C1N(C)CCC(O)(C=2C(=CC(Cl)=CC=2)Cl)C1C(O)C1=CC=C(Cl)C=C1Cl OVHJBARWJMLZJX-UHFFFAOYSA-N 0.000 claims description 8
- DZFHBQVAADZTER-UHFFFAOYSA-N [4-hydroxy-4-(4-iodophenyl)-1-methylpiperidin-3-yl]-(4-iodophenyl)methanone Chemical compound C1N(C)CCC(O)(C=2C=CC(I)=CC=2)C1C(=O)C1=CC=C(I)C=C1 DZFHBQVAADZTER-UHFFFAOYSA-N 0.000 claims description 8
- 230000009471 action Effects 0.000 claims description 8
- 125000003158 alcohol group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- FEIRROBBFMUCJM-UHFFFAOYSA-N (2,4-dichlorophenyl)-[4-(2,4-dichlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C(=CC(Cl)=CC=2)Cl)C1C(=O)C1=CC=C(Cl)C=C1Cl FEIRROBBFMUCJM-UHFFFAOYSA-N 0.000 claims description 7
- XDLDPJGYZCQYMY-UHFFFAOYSA-N (3,4-difluorophenyl)-[4-(3,4-difluorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=C(F)C(F)=CC=2)C1C(=O)C1=CC=C(F)C(F)=C1 XDLDPJGYZCQYMY-UHFFFAOYSA-N 0.000 claims description 7
- DWGVERMSVZMWCJ-UHFFFAOYSA-N (4-bromophenyl)-[4-(4-bromophenyl)-4-hydroxy-1-(3-phenylpropyl)piperidin-3-yl]methanone Chemical compound C1C(C(=O)C=2C=CC(Br)=CC=2)C(O)(C=2C=CC(Br)=CC=2)CCN1CCCC1=CC=CC=C1 DWGVERMSVZMWCJ-UHFFFAOYSA-N 0.000 claims description 7
- KOOJGXCUNDJTLP-UHFFFAOYSA-N (4-ethylphenyl)-[4-(4-ethylphenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1=CC(CC)=CC=C1C(=O)C1C(C=2C=CC(CC)=CC=2)(O)CCN(C)C1 KOOJGXCUNDJTLP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
- PLPZXLPNZHCGES-UHFFFAOYSA-N (4-bromophenyl)-[4-(4-bromophenyl)-4-hydroxy-1-(2-phenylethyl)piperidin-3-yl]methanone Chemical compound C1C(C(=O)C=2C=CC(Br)=CC=2)C(O)(C=2C=CC(Br)=CC=2)CCN1CCC1=CC=CC=C1 PLPZXLPNZHCGES-UHFFFAOYSA-N 0.000 claims description 6
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- LVNNUHJNCBWXHU-UHFFFAOYSA-N (3,4-dimethylphenyl)-[4-(3,4-dimethylphenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=C(C)C(C)=CC=2)C1C(=O)C1=CC=C(C)C(C)=C1 LVNNUHJNCBWXHU-UHFFFAOYSA-N 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 208000030814 Eating disease Diseases 0.000 claims description 4
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- SWFNNRQTSSTAGB-UHFFFAOYSA-N [4-hydroxy-1-methyl-4-(4-methylphenyl)piperidin-3-yl]-(4-methylphenyl)methanone Chemical compound C1N(C)CCC(O)(C=2C=CC(C)=CC=2)C1C(=O)C1=CC=C(C)C=C1 SWFNNRQTSSTAGB-UHFFFAOYSA-N 0.000 claims description 4
- 201000007930 alcohol dependence Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 235000014632 disordered eating Nutrition 0.000 claims description 4
- 230000002825 dopamine reuptake Effects 0.000 claims description 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- ADTJYHHPIOXMGN-UHFFFAOYSA-N [1-ethyl-4-hydroxy-4-(4-methylphenyl)piperidin-3-yl]-(4-methylphenyl)methanone Chemical compound C1N(CC)CCC(O)(C=2C=CC(C)=CC=2)C1C(=O)C1=CC=C(C)C=C1 ADTJYHHPIOXMGN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- QOVRJWXRDXIDQG-UHFFFAOYSA-N bis[4-(4-chloro-3-methylphenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound CN1CCC(O)(C(C1)C(=O)C1CN(C)CCC1(O)c1ccc(Cl)c(C)c1)c1ccc(Cl)c(C)c1 QOVRJWXRDXIDQG-UHFFFAOYSA-N 0.000 claims description 2
- LWMFMZKTEROARR-UHFFFAOYSA-N 3-[hydroxy-(4-methylphenyl)methyl]-1-methyl-4-(4-methylphenyl)piperidin-4-ol Chemical compound C1N(C)CCC(O)(C=2C=CC(C)=CC=2)C1C(O)C1=CC=C(C)C=C1 LWMFMZKTEROARR-UHFFFAOYSA-N 0.000 claims 6
- XNBVPNOKDZJGEC-UHFFFAOYSA-N (3,4-dichlorophenyl)-[4-(3,4-dichlorophenyl)-4-hydroxy-1-(3-phenylpropyl)piperidin-3-yl]methanone Chemical compound C1C(C(=O)C=2C=C(Cl)C(Cl)=CC=2)C(O)(C=2C=C(Cl)C(Cl)=CC=2)CCN1CCCC1=CC=CC=C1 XNBVPNOKDZJGEC-UHFFFAOYSA-N 0.000 claims 5
- UFHWOVCVCKOHGI-UHFFFAOYSA-N (4-chlorophenyl)-[4-(4-chlorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=CC(Cl)=CC=2)C1C(=O)C1=CC=C(Cl)C=C1 UFHWOVCVCKOHGI-UHFFFAOYSA-N 0.000 claims 5
- 238000011287 therapeutic dose Methods 0.000 claims 5
- 208000012902 Nervous system disease Diseases 0.000 claims 3
- SWFNNRQTSSTAGB-PZJWPPBQSA-N O=C([C@H]1[C@@](O)(CCN(C1)C)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 Chemical compound O=C([C@H]1[C@@](O)(CCN(C1)C)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 SWFNNRQTSSTAGB-PZJWPPBQSA-N 0.000 claims 2
- OIBZBHDPTVEFOC-UHFFFAOYSA-N 6-methyl-4,8a-bis(4-methylphenyl)-4,4a,5,6,7,8-hexahydrobenzo[d][1,3]dioxin-2-one Chemical compound C12CC(C)CCC2(C=2C=CC(C)=CC=2)OC(=O)OC1C1=CC=C(C)C=C1 OIBZBHDPTVEFOC-UHFFFAOYSA-N 0.000 claims 1
- BGZGKVAVORWNIY-UHFFFAOYSA-N 6-methyl-4,8a-bis(4-methylphenyl)-4a,5,7,8-tetrahydro-4h-[1,3]dioxino[5,4-c]pyridin-2-one Chemical compound C12CN(C)CCC2(C=2C=CC(C)=CC=2)OC(=O)OC1C1=CC=C(C)C=C1 BGZGKVAVORWNIY-UHFFFAOYSA-N 0.000 claims 1
- ZWPWLKXZYNXATK-UHFFFAOYSA-N bis(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(C)C=C1 ZWPWLKXZYNXATK-UHFFFAOYSA-N 0.000 claims 1
- QPYBMLSVFYCTJL-UHFFFAOYSA-N bis[4-(4-bromophenyl)-4-hydroxy-1-(3-phenylpropyl)piperidin-3-yl]methanone Chemical compound BrC1=CC=C(C=C1)C1(C(CN(CC1)CCCC1=CC=CC=C1)C(=O)C1CN(CCC1(C1=CC=C(C=C1)Br)O)CCCC1=CC=CC=C1)O QPYBMLSVFYCTJL-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 102
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 44
- 239000002253 acid Substances 0.000 abstract description 3
- 125000004429 atom Chemical group 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 150000001299 aldehydes Chemical class 0.000 abstract 2
- 125000003368 amide group Chemical group 0.000 abstract 2
- 150000002148 esters Chemical class 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 229920006395 saturated elastomer Polymers 0.000 abstract 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 abstract 2
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000027455 binding Effects 0.000 description 82
- 102100033928 Sodium-dependent dopamine transporter Human genes 0.000 description 56
- 101710114615 Sodium-dependent dopamine transporter Proteins 0.000 description 56
- 150000002611 lead compounds Chemical class 0.000 description 48
- 230000008485 antagonism Effects 0.000 description 46
- 230000003389 potentiating effect Effects 0.000 description 46
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- 238000012360 testing method Methods 0.000 description 39
- 229940126214 compound 3 Drugs 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 229910052799 carbon Inorganic materials 0.000 description 24
- 239000007787 solid Substances 0.000 description 22
- 239000000126 substance Substances 0.000 description 22
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 230000006742 locomotor activity Effects 0.000 description 18
- 239000005557 antagonist Substances 0.000 description 17
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
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- 210000004556 brain Anatomy 0.000 description 14
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
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- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 10
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- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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- 230000003042 antagnostic effect Effects 0.000 description 5
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
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- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
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- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical group C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 238000002328 two-dimensional heteronuclear correlation spectroscopy Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—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
- 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
- A61P25/24—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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15579799P | 1999-09-27 | 1999-09-27 | |
| US155797P | 1999-09-27 | ||
| US22658100P | 2000-08-21 | 2000-08-21 | |
| US226581P | 2000-08-21 | ||
| PCT/US2000/026447 WO2001022964A1 (en) | 1999-09-27 | 2000-09-27 | Dopamine transporter inhibitors and their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1242080A1 true EP1242080A1 (de) | 2002-09-25 |
| EP1242080A4 EP1242080A4 (de) | 2003-01-22 |
Family
ID=26852613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00968417A Withdrawn EP1242080A4 (de) | 1999-09-27 | 2000-09-27 | Inhibitoren von dopaminetransport und deren verwendung |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1242080A4 (de) |
| CA (1) | CA2389049A1 (de) |
| WO (1) | WO2001022964A1 (de) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| CA2469435A1 (en) | 2001-12-21 | 2003-07-24 | X-Ceptor Therapeutics, Inc. | Modulators of lxr |
| MX2009006334A (es) * | 2006-12-19 | 2009-06-23 | Hoffmann La Roche | Derivados de heteroaril-pirrolidinil- y -piperidinil-cetona. |
| KR20110010783A (ko) * | 2008-06-18 | 2011-02-07 | 에프. 호프만-라 로슈 아게 | Ｍｒｉ로서의 아릴 케톤 |
| EP3242872B1 (de) * | 2015-01-09 | 2019-07-03 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanon-derivate und verwandte verbindungen als inhibitoren der histon demethylase kdm2b zur behandlung von krebs |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998037078A1 (en) * | 1997-02-20 | 1998-08-27 | Novo Nordisk A/S | Solid phase and combinatorial synthesis of substituted thiophenes and of arrays of substituted thiophenes |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2489669A (en) * | 1947-01-11 | 1949-11-29 | Hoffamnn La Roche Inc | Preparation of 1-alkyl-3-benzoyl-4-hydroxy-4-phenyl-piperidines |
| FR1552758A (de) * | 1963-07-01 | 1969-01-10 | ||
| NL124853C (de) * | 1963-07-19 | |||
| US3317548A (en) * | 1964-10-30 | 1967-05-02 | Rexall Drug Chemical | 1-allyl-3-(substituted benzoyl)-4-(substituted phenyl)-4-hydroxypiperidines |
| US3408445A (en) * | 1967-04-10 | 1968-10-29 | Rexall Drug Chemical | Treatment of inflammation with 1-methyl - 3 - benzoyl - 4 - hydroxy - 4-phenylpiperidine and halo derivatives thereof |
| DE1670583A1 (de) * | 1967-11-02 | 1971-02-25 | Degussa | Neue Piperidinderivate |
| US3887568A (en) * | 1973-07-12 | 1975-06-03 | Riker Laboratories Inc | Process for piperidine derivatives |
| US3965104A (en) * | 1975-06-16 | 1976-06-22 | G. D. Searle & Co. | 1-(Substituted-aminoalkyl)-3-benzoyl-4-hydroxy-4-phenylpiperidines and related compounds |
| US5512584A (en) * | 1991-04-16 | 1996-04-30 | Basf Aktiengesellschaft | 1,3,4-trisubstituted piperidine derivatives, the preparation and use thereof |
| US6017933A (en) * | 1998-01-30 | 2000-01-25 | University Of Saskatchewan Technologies Inc. | Mannich bases of conjugated styryl ketones |
-
2000
- 2000-09-27 EP EP00968417A patent/EP1242080A4/de not_active Withdrawn
- 2000-09-27 WO PCT/US2000/026447 patent/WO2001022964A1/en not_active Application Discontinuation
- 2000-09-27 CA CA002389049A patent/CA2389049A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998037078A1 (en) * | 1997-02-20 | 1998-08-27 | Novo Nordisk A/S | Solid phase and combinatorial synthesis of substituted thiophenes and of arrays of substituted thiophenes |
Non-Patent Citations (5)
| Title |
|---|
| CASY, A.F. ET AL: "Phenindamine and its Analogues and Precursors: NMR Evidence of Structure and Configuration" MAGN. RESON. CHEM., vol. 30, no. 7, 1992, pages 621-625, XP009000566 * |
| DIMMOCK, J.R. ET AL: "4-(beta-Arylvinyl)-3-(beta-arylvinylketo) -1-ethyl-4-piperidinols ans Related Compounds: A Novel Class of Cytotoxic and Anticancer Agents" J. MED. CHEM., vol. 41, 1998, pages 4012-4020, XP002221590 * |
| GARCIA-MARCH, F.J. ET AL: "Pharmacological Sudies of 1-(p-Chlorophenyl)propanol and 2-(1-Hydroxy-3-butenyl)phenol: Two New Non-narcotic Analgesics Designed by Molecular Connectivity" J. PHARM. PHARMACOL., vol. 49, 1997, pages 10-15, XP009000642 * |
| See also references of WO0122964A1 * |
| STENLAKE, J.B. ET AL: "Synthesis and preliminary study of some ring-substituted arylpropanonamines and their quaternary salts" EUR. J. MED. CHEM., vol. 24, 1989, pages 591-597, XP009000568 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001022964A1 (en) | 2001-04-05 |
| CA2389049A1 (en) | 2001-04-05 |
| EP1242080A4 (de) | 2003-01-22 |
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