HRP20040952A2 - Isoquinoline derivatives - Google Patents
Isoquinoline derivativesInfo
- Publication number
- HRP20040952A2 HRP20040952A2 HR20040952A HRP20040952A HRP20040952A2 HR P20040952 A2 HRP20040952 A2 HR P20040952A2 HR 20040952 A HR20040952 A HR 20040952A HR P20040952 A HRP20040952 A HR P20040952A HR P20040952 A2 HRP20040952 A2 HR P20040952A2
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- benzyloxy
- alkyl
- dihydro
- isoquinolin
- Prior art date
Links
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 270
- 239000001257 hydrogen Substances 0.000 claims description 88
- 229910052739 hydrogen Inorganic materials 0.000 claims description 88
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- -1 3-[6-(4-cyano-benzyloxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-pentanoic acid Chemical compound 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 125000000524 functional group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- DGOTVLPWFOXKAF-UHFFFAOYSA-N 2-[6-[(4-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N(C(C)C(N)=O)CCC2=CC=1OCC1=CC=C(F)C=C1 DGOTVLPWFOXKAF-UHFFFAOYSA-N 0.000 claims 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 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- CYPPEHYWNOYMNA-LLVKDONJSA-N (2r)-2-[6-[(4-fluorophenyl)methoxy]-1,3-dioxo-4h-isoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@H](C)C(N)=O)C(=O)CC2=CC=1OCC1=CC=C(F)C=C1 CYPPEHYWNOYMNA-LLVKDONJSA-N 0.000 claims description 5
- DLBZEIVJJZYTLW-UHFFFAOYSA-N 2-[6-[(3-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N(C(C)C(N)=O)CCC2=CC=1OCC1=CC=CC(F)=C1 DLBZEIVJJZYTLW-UHFFFAOYSA-N 0.000 claims description 5
- DLBZEIVJJZYTLW-GFCCVEGCSA-N (2r)-2-[6-[(3-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@H](C)C(N)=O)CCC2=CC=1OCC1=CC=CC(F)=C1 DLBZEIVJJZYTLW-GFCCVEGCSA-N 0.000 claims description 4
- DGOTVLPWFOXKAF-LBPRGKRZSA-N (2s)-2-[6-[(4-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@@H](C)C(N)=O)CCC2=CC=1OCC1=CC=C(F)C=C1 DGOTVLPWFOXKAF-LBPRGKRZSA-N 0.000 claims description 4
- DHOUHDHHMBOHDG-UHFFFAOYSA-N 2-[6-[(3,4-difluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N(C(C)C(N)=O)CCC2=CC=1OCC1=CC=C(F)C(F)=C1 DHOUHDHHMBOHDG-UHFFFAOYSA-N 0.000 claims description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- DGOTVLPWFOXKAF-GFCCVEGCSA-N (2r)-2-[6-[(4-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@H](C)C(N)=O)CCC2=CC=1OCC1=CC=C(F)C=C1 DGOTVLPWFOXKAF-GFCCVEGCSA-N 0.000 claims description 3
- CYPPEHYWNOYMNA-NSHDSACASA-N (2s)-2-[6-[(4-fluorophenyl)methoxy]-1,3-dioxo-4h-isoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@@H](C)C(N)=O)C(=O)CC2=CC=1OCC1=CC=C(F)C=C1 CYPPEHYWNOYMNA-NSHDSACASA-N 0.000 claims description 3
- ODGWTYYKLMRDHO-KRWDZBQOSA-N (2s)-2-[6-[(4-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-3-hydroxypropanamide Chemical compound C=1C=C2C(=O)N([C@@H](CO)C(=O)N)CCC2=CC=1OCC1=CC=C(F)C=C1 ODGWTYYKLMRDHO-KRWDZBQOSA-N 0.000 claims description 3
- IMOGEGYGTIXNOJ-UHFFFAOYSA-N 2-[6-[(3-fluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]acetamide Chemical compound C=1C=C2C(=O)N(CC(=O)N)CCC2=CC=1OCC1=CC=CC(F)=C1 IMOGEGYGTIXNOJ-UHFFFAOYSA-N 0.000 claims description 3
- XIVPKAUDUKPCRN-UHFFFAOYSA-N 2-[6-[(3-fluorophenyl)methoxy]-3,4-dihydro-1h-isoquinolin-2-yl]acetamide Chemical class C=1C=C2CN(CC(=O)N)CCC2=CC=1OCC1=CC=CC(F)=C1 XIVPKAUDUKPCRN-UHFFFAOYSA-N 0.000 claims description 3
- YZWURNJMOSJECE-UHFFFAOYSA-N 2-[6-[(4-fluorophenyl)methoxy]-3,4-dihydro-1h-isoquinolin-2-yl]propanamide Chemical compound C=1C=C2CN(C(C)C(N)=O)CCC2=CC=1OCC1=CC=C(F)C=C1 YZWURNJMOSJECE-UHFFFAOYSA-N 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 229940052764 dopaminergic anti-parkinson drug mao b inhibitors Drugs 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- WSCUQKVFDWSWKP-LLVKDONJSA-N (2r)-2-[6-[(2,6-difluorophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanamide Chemical compound C=1C=C2C(=O)N([C@H](C)C(N)=O)CCC2=CC=1OCC1=C(F)C=CC=C1F WSCUQKVFDWSWKP-LLVKDONJSA-N 0.000 claims description 2
- DGSOEQBFSBHRJZ-UHFFFAOYSA-N 2-[6-[(3-fluorophenyl)methoxy]-3,4-dihydro-1h-isoquinolin-2-yl]propanamide Chemical compound C=1C=C2CN(C(C)C(N)=O)CCC2=CC=1OCC1=CC=CC(F)=C1 DGSOEQBFSBHRJZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 230000006806 disease prevention Effects 0.000 claims 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- BLLNWSQDPZSKGA-UHFFFAOYSA-N tert-butyl 2-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]acetate Chemical compound C=1C=C2C(=O)N(CC(=O)OC(C)(C)C)CCC2=CC=1OCC1=CC=C(C#N)C=C1 BLLNWSQDPZSKGA-UHFFFAOYSA-N 0.000 claims 1
- OSAPFULEPXMRSO-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-6-ethoxyhexanoate Chemical compound C=1C=C2C(=O)N(C(CC(=O)OC(C)(C)C)CCCOCC)CCC2=CC=1OCC1=CC=C(C#N)C=C1 OSAPFULEPXMRSO-UHFFFAOYSA-N 0.000 claims 1
- QZGJGUWVWPYBIO-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-6-methoxyhexanoate Chemical compound C=1C=C2C(=O)N(C(CC(=O)OC(C)(C)C)CCCOC)CCC2=CC=1OCC1=CC=C(C#N)C=C1 QZGJGUWVWPYBIO-UHFFFAOYSA-N 0.000 claims 1
- BSLWARRUEHBLTH-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]hexanoate Chemical compound C=1C=C2C(=O)N(C(CC(=O)OC(C)(C)C)CCC)CCC2=CC=1OCC1=CC=C(C#N)C=C1 BSLWARRUEHBLTH-UHFFFAOYSA-N 0.000 claims 1
- RFNPAAUNHBZAFZ-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]nonanoate Chemical compound C=1C=C2C(=O)N(C(CC(=O)OC(C)(C)C)CCCCCC)CCC2=CC=1OCC1=CC=C(C#N)C=C1 RFNPAAUNHBZAFZ-UHFFFAOYSA-N 0.000 claims 1
- FSUSOAHPHBQPLC-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]octanoate Chemical compound C=1C=C2C(=O)N(C(CC(=O)OC(C)(C)C)CCCCC)CCC2=CC=1OCC1=CC=C(C#N)C=C1 FSUSOAHPHBQPLC-UHFFFAOYSA-N 0.000 claims 1
- KJZLTMFCYTYPBP-UHFFFAOYSA-N tert-butyl 3-[6-[(4-cyanophenyl)methoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]propanoate Chemical compound C=1C=C2C(=O)N(CCC(=O)OC(C)(C)C)CCC2=CC=1OCC1=CC=C(C#N)C=C1 KJZLTMFCYTYPBP-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000000203 mixture Substances 0.000 description 74
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- 102000010909 Monoamine Oxidase Human genes 0.000 description 31
- 108010062431 Monoamine oxidase Proteins 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 229940080818 propionamide Drugs 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 238000001914 filtration Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 238000001035 drying Methods 0.000 description 14
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 14
- AUHYZQCEIVEMFH-UHFFFAOYSA-N 2-bromopropanamide Chemical compound CC(Br)C(N)=O AUHYZQCEIVEMFH-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 235000011181 potassium carbonates Nutrition 0.000 description 13
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 12
- ZQELSSWRGNGPGR-UHFFFAOYSA-N 2-[5-[(4-fluorophenyl)methoxy]-2-iodophenyl]acetaldehyde Chemical compound C1=CC(F)=CC=C1COC1=CC=C(I)C(CC=O)=C1 ZQELSSWRGNGPGR-UHFFFAOYSA-N 0.000 description 11
- 229910052786 argon Inorganic materials 0.000 description 11
- DUBYHOLRDXMYAY-UHFFFAOYSA-N 6-[(3-fluorophenyl)methoxy]-3,4-dihydro-2h-isoquinolin-1-one Chemical compound FC1=CC=CC(COC=2C=C3CCNC(=O)C3=CC=2)=C1 DUBYHOLRDXMYAY-UHFFFAOYSA-N 0.000 description 9
- WLKRVRVEWWCOJJ-UHFFFAOYSA-N 6-[(4-fluorophenyl)methoxy]-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC(F)=CC=C1COC1=CC=C(CNCC2)C2=C1 WLKRVRVEWWCOJJ-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000002349 favourable effect Effects 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- WVANQPZQCOXLDS-UHFFFAOYSA-N 6-[(3-fluorophenyl)methoxy]-1,2,3,4-tetrahydroisoquinoline Chemical compound FC1=CC=CC(COC=2C=C3CCNCC3=CC=2)=C1 WVANQPZQCOXLDS-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 6
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 229910052681 coesite Inorganic materials 0.000 description 5
- 229910052906 cristobalite Inorganic materials 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 229910052682 stishovite Inorganic materials 0.000 description 5
- 229910052905 tridymite Inorganic materials 0.000 description 5
- VRVMCMKBIBYJDV-UHFFFAOYSA-N 2-[5-[(4-fluorophenyl)methoxy]-2-iodophenyl]acetic acid Chemical compound C1=C(I)C(CC(=O)O)=CC(OCC=2C=CC(F)=CC=2)=C1 VRVMCMKBIBYJDV-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- FVMDYYGIDFPZAX-UHFFFAOYSA-N 3-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=CC(O)=C1 FVMDYYGIDFPZAX-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- QMNQLSIZPHQEMU-UHFFFAOYSA-N 6-[(4-fluorophenyl)methoxy]-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1=CC(F)=CC=C1COC1=CC=C(C(=O)NCC2)C2=C1 QMNQLSIZPHQEMU-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- 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
- A61P25/14—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
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical 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)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02009253 | 2002-04-26 | ||
| PCT/EP2003/003845 WO2003091219A1 (en) | 2002-04-26 | 2003-04-14 | Isoquinoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20040952A2 true HRP20040952A2 (en) | 2005-06-30 |
Family
ID=29265896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20040952A HRP20040952A2 (en) | 2002-04-26 | 2004-10-12 | Isoquinoline derivatives |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US6818774B2 (es) |
| EP (1) | EP1501804B1 (es) |
| JP (1) | JP4322685B2 (es) |
| KR (1) | KR100681585B1 (es) |
| CN (1) | CN1310890C (es) |
| AR (1) | AR039651A1 (es) |
| AT (1) | ATE440821T1 (es) |
| AU (1) | AU2003227614B2 (es) |
| BR (1) | BR0309562A (es) |
| CA (1) | CA2483461C (es) |
| DE (1) | DE60328978D1 (es) |
| DK (1) | DK1501804T3 (es) |
| ES (1) | ES2329354T3 (es) |
| GT (1) | GT200300095A (es) |
| HK (1) | HK1080836A1 (es) |
| HR (1) | HRP20040952A2 (es) |
| IL (1) | IL164677A0 (es) |
| MX (1) | MXPA04010537A (es) |
| MY (1) | MY133527A (es) |
| NO (1) | NO20044571L (es) |
| NZ (1) | NZ535885A (es) |
| PA (1) | PA8572001A1 (es) |
| PE (1) | PE20040594A1 (es) |
| PL (1) | PL373697A1 (es) |
| PT (1) | PT1501804E (es) |
| RU (1) | RU2318812C2 (es) |
| SI (1) | SI1501804T1 (es) |
| TW (1) | TWI278451B (es) |
| UY (1) | UY27786A1 (es) |
| WO (1) | WO2003091219A1 (es) |
| ZA (1) | ZA200408281B (es) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| JP4728962B2 (ja) * | 2003-05-19 | 2011-07-20 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 免疫抑制化合物および組成物 |
| EP1638551B1 (en) * | 2003-05-19 | 2011-12-21 | Irm Llc | Immunosuppressant compounds and compositions |
| MXPA06002310A (es) | 2003-08-29 | 2006-05-25 | Ono Pharmaceutical Co | Compuesto capaz de enlazarse al receptor s1p y uso farmaceutico del mismo. |
| CN101407471A (zh) | 2003-08-29 | 2009-04-15 | 小野药品工业株式会社 | 能够结合s1p受体的化合物及其药物用途 |
| CA2543287A1 (en) * | 2003-10-23 | 2005-05-06 | F.Hoffmann-La Roche Ag | Benzazepine derivatives as mao-b inhibitors |
| SI1751111T1 (sl) | 2004-03-01 | 2015-04-30 | Actelion Pharmaceuticals Ltd. | Substituirani 1,2,3,4-tetrahidroizokinolinski derivati |
| PL1826197T3 (pl) | 2004-12-13 | 2012-06-29 | Ono Pharmaceutical Co | Pochodna kwasu aminokarboksylowego i jej zastosowanie lecznicze |
| CA2595339C (en) * | 2005-01-28 | 2014-08-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Method for producing isochromane and derivatives thereof |
| UA90708C2 (ru) | 2005-02-25 | 2010-05-25 | Ф. Хоффманн-Ля Рош Аг | Таблетки с улучшенной дисперсностью лекарственного вещества |
| NZ567540A (en) | 2005-12-22 | 2010-07-30 | Newron Pharm Spa | 2-Phenylethylamino derivatives as calcium and/or sodium channel modulators |
| MX2008011647A (es) * | 2006-03-15 | 2008-09-22 | Actelion Pharmaceuticals Ltd | Derivados de tetrahidroisoquinolina para mejorar la funcion de la memoria. |
| WO2007122591A2 (en) | 2006-04-26 | 2007-11-01 | Actelion Pharmaceuticals Ltd | Pyrazolo-tetrahydro pyridine derivatives as orexin receptor antagonists |
| KR101220182B1 (ko) | 2009-02-25 | 2013-01-11 | 에스케이바이오팜 주식회사 | 치환된 아졸 유도체 화합물, 이를 포함하는 약제학적 조성물 및 이를 이용한 파킨슨씨 병 치료방법 |
| CN105315204B (zh) * | 2014-07-04 | 2018-02-09 | 中南大学 | 7‑氨基‑1,4‑二氢异喹啉‑3(2h)‑酮衍生物及其合成方法和用途 |
| CN105585527B (zh) * | 2015-12-17 | 2018-06-26 | 浙江工业大学 | 2-(3,4-二氢异喹啉-1(2h)-亚基)乙腈类化合物及其应用 |
| CN105461626B (zh) * | 2015-12-17 | 2018-05-08 | 浙江工业大学 | 芳环或稠杂环联3,4-二氢异喹啉类共轭结构化合物及其应用 |
| WO2018183171A1 (en) * | 2017-03-27 | 2018-10-04 | Bristol-Myers Squibb Company | Substituted isoquionline derivatives as immunomudulators |
| CN114591238B (zh) * | 2022-03-25 | 2022-11-15 | 邦恩泰(山东)生物医药科技集团股份有限公司 | 一种异喹啉类药物中间体的合成方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6448269B1 (en) * | 1993-07-22 | 2002-09-10 | Eli Lilly And Company | Glycoprotein IIb/IIIa antagonists |
| US5731324A (en) * | 1993-07-22 | 1998-03-24 | Eli Lilly And Company | Glycoprotein IIb/IIIa antagonists |
| US6137002A (en) * | 1993-07-22 | 2000-10-24 | Eli Lilly And Company | Glycoprotein IIb/IIIa antagonists |
| IL110172A (en) * | 1993-07-22 | 2001-10-31 | Lilly Co Eli | Bicycle compounds and pharmaceuticals containing them |
| US5679715A (en) | 1995-06-07 | 1997-10-21 | Harris; Richard Y. | Method for treating multiple sclerosis |
| WO1997033572A1 (en) | 1996-03-15 | 1997-09-18 | Somerset Pharmaceuticals, Inc. | Method for preventing and treating peripheral neurophathy by administering selegiline |
| WO2001034172A2 (en) | 1999-11-05 | 2001-05-17 | Vela Pharmaceuticals Inc. | Methods and compositions for treating reward deficiency syndrome |
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2003
- 2003-04-14 ES ES03725018T patent/ES2329354T3/es not_active Expired - Lifetime
- 2003-04-14 NZ NZ535885A patent/NZ535885A/en not_active IP Right Cessation
- 2003-04-14 EP EP03725018A patent/EP1501804B1/en not_active Expired - Lifetime
- 2003-04-14 KR KR1020047017185A patent/KR100681585B1/ko not_active IP Right Cessation
- 2003-04-14 CA CA2483461A patent/CA2483461C/en not_active Expired - Fee Related
- 2003-04-14 PL PL03373697A patent/PL373697A1/xx unknown
- 2003-04-14 WO PCT/EP2003/003845 patent/WO2003091219A1/en active Application Filing
- 2003-04-14 RU RU2004134575/04A patent/RU2318812C2/ru not_active IP Right Cessation
- 2003-04-14 DE DE60328978T patent/DE60328978D1/de not_active Expired - Lifetime
- 2003-04-14 PT PT03725018T patent/PT1501804E/pt unknown
- 2003-04-14 MX MXPA04010537A patent/MXPA04010537A/es active IP Right Grant
- 2003-04-14 AU AU2003227614A patent/AU2003227614B2/en not_active Ceased
- 2003-04-14 SI SI200331658T patent/SI1501804T1/sl unknown
- 2003-04-14 JP JP2003587782A patent/JP4322685B2/ja not_active Expired - Fee Related
- 2003-04-14 AT AT03725018T patent/ATE440821T1/de not_active IP Right Cessation
- 2003-04-14 CN CNB038093766A patent/CN1310890C/zh not_active Expired - Fee Related
- 2003-04-14 BR BR0309562-2A patent/BR0309562A/pt not_active IP Right Cessation
- 2003-04-14 DK DK03725018T patent/DK1501804T3/da active
- 2003-04-16 US US10/417,378 patent/US6818774B2/en not_active Expired - Fee Related
- 2003-04-23 TW TW092109478A patent/TWI278451B/zh not_active IP Right Cessation
- 2003-04-23 PA PA20038572001A patent/PA8572001A1/es unknown
- 2003-04-24 PE PE2003000408A patent/PE20040594A1/es not_active Application Discontinuation
- 2003-04-24 AR ARP030101412A patent/AR039651A1/es unknown
- 2003-04-24 GT GT200300095A patent/GT200300095A/es unknown
- 2003-04-25 MY MYPI20031578A patent/MY133527A/en unknown
- 2003-04-28 UY UY27786A patent/UY27786A1/es not_active Application Discontinuation
-
2004
- 2004-10-12 HR HR20040952A patent/HRP20040952A2/hr not_active Application Discontinuation
- 2004-10-13 ZA ZA200408281A patent/ZA200408281B/xx unknown
- 2004-10-18 IL IL16467704A patent/IL164677A0/xx not_active IP Right Cessation
- 2004-10-22 NO NO20044571A patent/NO20044571L/no not_active Application Discontinuation
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2006
- 2006-01-13 HK HK06100541A patent/HK1080836A1/xx not_active IP Right Cessation
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