JP2003523992A - 新規フェニルヘテロアリールアルキルアミン誘導体 - Google Patents
新規フェニルヘテロアリールアルキルアミン誘導体Info
- Publication number
- JP2003523992A JP2003523992A JP2001561723A JP2001561723A JP2003523992A JP 2003523992 A JP2003523992 A JP 2003523992A JP 2001561723 A JP2001561723 A JP 2001561723A JP 2001561723 A JP2001561723 A JP 2001561723A JP 2003523992 A JP2003523992 A JP 2003523992A
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- formula
- benzonitrile
- compound
- amino
- 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- Withdrawn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
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 238000000034 method Methods 0.000 claims abstract description 95
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 27
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 25
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 12
- 229910052720 vanadium Inorganic materials 0.000 claims abstract description 12
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 9
- -1 NR 6 R 7 Chemical group 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229940111134 coxibs Drugs 0.000 claims description 6
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- RFNWSUKUCZJGFZ-MRXNPFEDSA-N (4r)-4-(2,5-dichlorophenoxy)-4-(4-fluorophenyl)-n-methylbutan-1-amine Chemical compound O([C@H](CCCNC)C=1C=CC(F)=CC=1)C1=CC(Cl)=CC=C1Cl RFNWSUKUCZJGFZ-MRXNPFEDSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 230000009286 beneficial effect Effects 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- KMECBOCJLJFKTJ-INIZCTEOSA-N (3r)-3-(2,5-dichlorophenoxy)-n-methyl-4-(4-methylphenyl)butan-1-amine Chemical compound C([C@H](CCNC)OC=1C(=CC=C(Cl)C=1)Cl)C1=CC=C(C)C=C1 KMECBOCJLJFKTJ-INIZCTEOSA-N 0.000 claims description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- JXTJXWVYFOIRGC-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]piperazine Chemical compound ClC1=CC=C(Cl)C(OC(CCCN2CCNCC2)C=2C=CC=CC=2)=C1 JXTJXWVYFOIRGC-UHFFFAOYSA-N 0.000 claims description 2
- RRBQJTSKEIWUJL-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]piperidin-4-ol Chemical compound C1CC(O)CCN1CCCC(C=1C=CC=CC=1)OC1=CC(Cl)=CC=C1Cl RRBQJTSKEIWUJL-UHFFFAOYSA-N 0.000 claims description 2
- ZZKHGFVETXSRDK-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-thiophen-2-ylbutyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CCCC(C=1SC=CC=1)OC1=CC(Cl)=CC=C1Cl ZZKHGFVETXSRDK-UHFFFAOYSA-N 0.000 claims description 2
- UBTIFTSQKLAYOE-UHFFFAOYSA-N 2-[(1-amino-6-methylheptan-4-yl)amino]-4-(trifluoromethyl)benzonitrile Chemical compound NCCCC(CC(C)C)NC1=CC(C(F)(F)F)=CC=C1C#N UBTIFTSQKLAYOE-UHFFFAOYSA-N 0.000 claims description 2
- JNNQAKOEHNBNET-CQSZACIVSA-N 2-[(1r)-4-amino-1-(furan-3-yl)butoxy]-4-chloro-5-fluorobenzonitrile Chemical compound O([C@H](CCCN)C1=COC=C1)C1=CC(Cl)=C(F)C=C1C#N JNNQAKOEHNBNET-CQSZACIVSA-N 0.000 claims description 2
- PLDOAPUZJMTNCD-UHFFFAOYSA-N 2-[(4-amino-1-phenylbutyl)amino]-4-chlorobenzonitrile Chemical compound C=1C=CC=CC=1C(CCCN)NC1=CC(Cl)=CC=C1C#N PLDOAPUZJMTNCD-UHFFFAOYSA-N 0.000 claims description 2
- GDTQOEMSLHKILE-UHFFFAOYSA-N 2-[4-amino-1-(1,3-thiazol-2-yl)butoxy]-4-chlorobenzonitrile Chemical compound N=1C=CSC=1C(CCCN)OC1=CC(Cl)=CC=C1C#N GDTQOEMSLHKILE-UHFFFAOYSA-N 0.000 claims description 2
- QCHUYECHYFCHLQ-UHFFFAOYSA-N 2-[4-amino-1-(2-methoxypyridin-3-yl)butoxy]-4-chlorobenzonitrile Chemical compound COC1=NC=CC=C1C(CCCN)OC1=CC(Cl)=CC=C1C#N QCHUYECHYFCHLQ-UHFFFAOYSA-N 0.000 claims description 2
- BIHUPSJDIQBJMG-UHFFFAOYSA-N 2-[4-amino-1-(2-oxo-1h-pyridin-3-yl)butoxy]-4-chlorobenzonitrile Chemical compound C=1C=CNC(=O)C=1C(CCCN)OC1=CC(Cl)=CC=C1C#N BIHUPSJDIQBJMG-UHFFFAOYSA-N 0.000 claims description 2
- IVHMMFHIQCJCEB-UHFFFAOYSA-N 2-[4-amino-1-(furan-3-yl)butoxy]-4-chlorobenzonitrile Chemical compound C1=COC=C1C(CCCN)OC1=CC(Cl)=CC=C1C#N IVHMMFHIQCJCEB-UHFFFAOYSA-N 0.000 claims description 2
- QBQXIVSTBUZLOG-UHFFFAOYSA-N 2-[[4-(2,5-dichlorophenoxy)-4-phenylbutyl]-methylamino]ethanol Chemical compound C=1C=CC=CC=1C(CCCN(CCO)C)OC1=CC(Cl)=CC=C1Cl QBQXIVSTBUZLOG-UHFFFAOYSA-N 0.000 claims description 2
- WMGALHHWGZJOKF-UHFFFAOYSA-N 4-(2,5-dichlorophenoxy)-n-methyl-4-thiophen-2-ylbutan-1-amine Chemical compound C=1C=CSC=1C(CCCNC)OC1=CC(Cl)=CC=C1Cl WMGALHHWGZJOKF-UHFFFAOYSA-N 0.000 claims description 2
- ICJONTSMLLXXCO-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenoxy]-4-(1,3-thiazol-2-yl)butan-1-amine Chemical compound N=1C=CSC=1C(CCCN)OC1=CC(C(F)(F)F)=CC=C1Cl ICJONTSMLLXXCO-UHFFFAOYSA-N 0.000 claims description 2
- PFFMNXUIZGUQAZ-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenoxy]-4-(2-methyl-1,2,4-triazol-3-yl)butan-1-amine Chemical compound CN1N=CN=C1C(CCCN)OC1=CC(C(F)(F)F)=CC=C1Cl PFFMNXUIZGUQAZ-UHFFFAOYSA-N 0.000 claims description 2
- VGFNLQZVFKBTPY-JOCHJYFZSA-N 4-chloro-2-[(1r)-1-phenyl-4-(pyridin-3-ylmethylamino)butoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNCC=2C=NC=CC=2)C=2C=CC=CC=2)=C1 VGFNLQZVFKBTPY-JOCHJYFZSA-N 0.000 claims description 2
- UOZARJXEZPWSBH-HXUWFJFHSA-N 4-chloro-2-[(1r)-1-phenyl-4-pyrrolidin-1-ylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2CCCC2)C=2C=CC=CC=2)=C1 UOZARJXEZPWSBH-HXUWFJFHSA-N 0.000 claims description 2
- FAQOVRHAGUJGJJ-GOSISDBHSA-N 4-chloro-2-[(1r)-4-(2-hydroxyethylamino)-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCNCCO)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N FAQOVRHAGUJGJJ-GOSISDBHSA-N 0.000 claims description 2
- FQHJXPDAFFSZLM-LJQANCHMSA-N 4-chloro-2-[(1r)-4-(3-hydroxypropylamino)-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCNCCCO)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N FQHJXPDAFFSZLM-LJQANCHMSA-N 0.000 claims description 2
- UKNKORSKHIJECC-LJQANCHMSA-N 4-chloro-2-[(1r)-4-(cyclopropylamino)-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNC2CC2)C=2C=CC=CC=2)=C1 UKNKORSKHIJECC-LJQANCHMSA-N 0.000 claims description 2
- FXXVGHDSDZQSIZ-OAQYLSRUSA-N 4-chloro-2-[(1r)-4-[2-(1h-imidazol-5-yl)ethylamino]-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNCCC=2NC=NC=2)C=2C=CC=CC=2)=C1 FXXVGHDSDZQSIZ-OAQYLSRUSA-N 0.000 claims description 2
- SIHYEEYEMBGQOD-DNVCBOLYSA-N 4-chloro-2-[(1r)-4-[[(2r)-1-hydroxypropan-2-yl]amino]-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCN[C@@H](CO)C)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N SIHYEEYEMBGQOD-DNVCBOLYSA-N 0.000 claims description 2
- BEHQHZICCZXWAO-HXUWFJFHSA-N 4-chloro-2-[(1r)-4-[ethyl(2-hydroxyethyl)amino]-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCN(CCO)CC)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N BEHQHZICCZXWAO-HXUWFJFHSA-N 0.000 claims description 2
- PTFCRSMCXDMEMX-LJQANCHMSA-N 4-chloro-2-[(1r)-4-imidazol-1-yl-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2C=NC=C2)C=2C=CC=CC=2)=C1 PTFCRSMCXDMEMX-LJQANCHMSA-N 0.000 claims description 2
- YCBPABBMUOXUTK-HXUWFJFHSA-N 4-chloro-2-[(1r)-4-morpholin-4-yl-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2CCOCC2)C=2C=CC=CC=2)=C1 YCBPABBMUOXUTK-HXUWFJFHSA-N 0.000 claims description 2
- JQRGYJPOOIXAHS-UHFFFAOYSA-N 4-chloro-2-[1-(furan-2-yl)-4-(methylamino)butoxy]benzonitrile Chemical compound C=1C=COC=1C(CCCNC)OC1=CC(Cl)=CC=C1C#N JQRGYJPOOIXAHS-UHFFFAOYSA-N 0.000 claims description 2
- HTRWYKSUHJPUCZ-UHFFFAOYSA-N 4-chloro-2-[1-(furan-3-yl)-4-(methylamino)butoxy]benzonitrile Chemical compound C1=COC=C1C(CCCNC)OC1=CC(Cl)=CC=C1C#N HTRWYKSUHJPUCZ-UHFFFAOYSA-N 0.000 claims description 2
- ZOXZOHSSFMBIBR-UHFFFAOYSA-N 4-chloro-2-[4-(ethylamino)-1-pyridin-2-ylbutoxy]benzonitrile Chemical compound C=1C=CC=NC=1C(CCCNCC)OC1=CC(Cl)=CC=C1C#N ZOXZOHSSFMBIBR-UHFFFAOYSA-N 0.000 claims description 2
- UHQJWLBEUOILOD-UHFFFAOYSA-N 4-chloro-2-[4-(methylamino)-1-pyridin-2-ylbutoxy]benzonitrile Chemical compound C=1C=CC=NC=1C(CCCNC)OC1=CC(Cl)=CC=C1C#N UHQJWLBEUOILOD-UHFFFAOYSA-N 0.000 claims description 2
- LDXIPWPOZJKKFF-UHFFFAOYSA-N 4-chloro-2-[4-(methylamino)-1-pyridin-4-ylbutoxy]benzonitrile Chemical compound C=1C=NC=CC=1C(CCCNC)OC1=CC(Cl)=CC=C1C#N LDXIPWPOZJKKFF-UHFFFAOYSA-N 0.000 claims description 2
- ZNWRXFGRRLWBKK-UHFFFAOYSA-N 4-chloro-2-[4-(methylamino)-1-thiophen-3-ylbutoxy]benzonitrile Chemical compound C1=CSC=C1C(CCCNC)OC1=CC(Cl)=CC=C1C#N ZNWRXFGRRLWBKK-UHFFFAOYSA-N 0.000 claims description 2
- UTTARCOGRMPBHU-OAHLLOKOSA-N 4-chloro-5-fluoro-2-[(1r)-1-(furan-3-yl)-4-(methylamino)butoxy]benzonitrile Chemical compound O([C@H](CCCNC)C1=COC=C1)C1=CC(Cl)=C(F)C=C1C#N UTTARCOGRMPBHU-OAHLLOKOSA-N 0.000 claims description 2
- UQQMUHUYOAGIED-UHFFFAOYSA-N 4-chloro-5-fluoro-2-[4-(methylamino)-1-pyridin-2-ylbutoxy]benzonitrile Chemical compound C=1C=CC=NC=1C(CCCNC)OC1=CC(Cl)=C(F)C=C1C#N UQQMUHUYOAGIED-UHFFFAOYSA-N 0.000 claims description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 1
- 239000003205 fragrance Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 53
- 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 abstract description 9
- 239000003112 inhibitor Substances 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 206010065390 Inflammatory pain Diseases 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
- 239000000047 product Substances 0.000 description 102
- 239000000243 solution Substances 0.000 description 101
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 62
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 37
- 239000002904 solvent Substances 0.000 description 35
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
- 239000000284 extract Substances 0.000 description 33
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 28
- 239000000377 silicon dioxide Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000012230 colorless oil Substances 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 22
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 22
- 238000004587 chromatography analysis Methods 0.000 description 22
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 229910021529 ammonia Inorganic materials 0.000 description 17
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- SMUWKRUWTDAYKS-UHFFFAOYSA-N 4-chloro-2-hydroxybenzonitrile Chemical compound OC1=CC(Cl)=CC=C1C#N SMUWKRUWTDAYKS-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 239000001530 fumaric acid Substances 0.000 description 9
- 229960002598 fumaric acid Drugs 0.000 description 9
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- JEBNSNUCJQJJJT-UHFFFAOYSA-N tert-butyl n-[4-(5-chloro-2-cyanophenoxy)-4-(1,3-thiazol-2-yl)butyl]carbamate Chemical compound N=1C=CSC=1C(CCCNC(=O)OC(C)(C)C)OC1=CC(Cl)=CC=C1C#N JEBNSNUCJQJJJT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0004149.1A GB0004149D0 (en) | 2000-02-23 | 2000-02-23 | Novel compounds |
| GB0004149.1 | 2000-02-23 | ||
| PCT/SE2001/000370 WO2001062713A1 (en) | 2000-02-23 | 2001-02-20 | Novel phenylheteroalkylamine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003523992A true JP2003523992A (ja) | 2003-08-12 |
| JP2003523992A5 JP2003523992A5 (enExample) | 2008-04-10 |
Family
ID=9886161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001561723A Withdrawn JP2003523992A (ja) | 2000-02-23 | 2001-02-20 | 新規フェニルヘテロアリールアルキルアミン誘導体 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6743939B2 (enExample) |
| EP (1) | EP1263714B1 (enExample) |
| JP (1) | JP2003523992A (enExample) |
| AR (1) | AR028220A1 (enExample) |
| AT (1) | ATE265422T1 (enExample) |
| AU (1) | AU2001234313A1 (enExample) |
| CO (1) | CO5290257A1 (enExample) |
| DE (1) | DE60103033T2 (enExample) |
| GB (1) | GB0004149D0 (enExample) |
| WO (1) | WO2001062713A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0004152D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0202280D0 (sv) | 2002-07-19 | 2002-07-19 | Astrazeneca Ab | Novel compounds |
| SE0202279D0 (sv) * | 2002-07-19 | 2002-07-19 | Astrazeneca Ab | Novel comppounds |
| SE0203304D0 (sv) * | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Coumpounds |
| JP5682051B2 (ja) | 2006-05-18 | 2015-03-11 | ファーマサイクリックス,インク. | 細胞内キナーゼ阻害剤 |
| DE102006031813B4 (de) * | 2006-07-07 | 2011-04-28 | Christian-Albrechts-Universität Zu Kiel | Verwendung basischer Acetophenone als Hemmstoffe von NO-Synthasen |
| WO2014112646A1 (ja) | 2013-01-21 | 2014-07-24 | 国立大学法人大阪大学 | フェノキシアルキルアミン化合物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52941B1 (enExample) | 1969-12-09 | 1977-01-11 | ||
| JPS5144934B1 (enExample) | 1969-12-09 | 1976-12-01 | ||
| US4314081A (en) | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| FR2432500A1 (fr) * | 1978-02-24 | 1980-02-29 | Roussel Uclaf | Nouveaux derives de la benzene propanamine et leurs sels, procede de preparation et application a titre de medicaments |
| KR880007433A (ko) * | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
| US4902710A (en) | 1988-12-14 | 1990-02-20 | Eli Lilly And Company | Serotonin and norepinephrine uptake inhibitors |
| US5320825A (en) | 1991-05-01 | 1994-06-14 | Trustees Of The University Of Pennsylvania | Serotonin reuptake inhibitors for S.P.E.C.T. imaging |
| EP0576766A1 (en) | 1992-06-29 | 1994-01-05 | Novo Nordisk A/S | Propanolamine derivatives, their preparation and use |
| HN1998000118A (es) | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| HN1998000125A (es) | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
| HUP0102236A3 (en) | 1998-06-03 | 2003-01-28 | Pfizer Prod Inc | 2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors and pharmaceutical compositions containing them and their use |
-
2000
- 2000-02-23 GB GBGB0004149.1A patent/GB0004149D0/en not_active Ceased
-
2001
- 2001-02-20 AU AU2001234313A patent/AU2001234313A1/en not_active Abandoned
- 2001-02-20 AT AT01906490T patent/ATE265422T1/de not_active IP Right Cessation
- 2001-02-20 CO CO01013432A patent/CO5290257A1/es not_active Application Discontinuation
- 2001-02-20 DE DE60103033T patent/DE60103033T2/de not_active Expired - Fee Related
- 2001-02-20 WO PCT/SE2001/000370 patent/WO2001062713A1/en not_active Ceased
- 2001-02-20 JP JP2001561723A patent/JP2003523992A/ja not_active Withdrawn
- 2001-02-20 US US10/204,815 patent/US6743939B2/en not_active Expired - Fee Related
- 2001-02-20 EP EP01906490A patent/EP1263714B1/en not_active Expired - Lifetime
- 2001-02-21 AR ARP010100772A patent/AR028220A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CO5290257A1 (es) | 2003-06-27 |
| AR028220A1 (es) | 2003-04-30 |
| GB0004149D0 (en) | 2000-04-12 |
| WO2001062713A1 (en) | 2001-08-30 |
| EP1263714A1 (en) | 2002-12-11 |
| EP1263714B1 (en) | 2004-04-28 |
| AU2001234313A1 (en) | 2001-09-03 |
| US20030105161A1 (en) | 2003-06-05 |
| ATE265422T1 (de) | 2004-05-15 |
| DE60103033D1 (de) | 2004-06-03 |
| US6743939B2 (en) | 2004-06-01 |
| DE60103033T2 (de) | 2005-04-28 |
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