ES2397764T3 - Tetrahidroisoquinolinas, composiciones farmacéuticas que las contienen, y su uso en terapia - Google Patents
Tetrahidroisoquinolinas, composiciones farmacéuticas que las contienen, y su uso en terapia Download PDFInfo
- Publication number
- ES2397764T3 ES2397764T3 ES09727055T ES09727055T ES2397764T3 ES 2397764 T3 ES2397764 T3 ES 2397764T3 ES 09727055 T ES09727055 T ES 09727055T ES 09727055 T ES09727055 T ES 09727055T ES 2397764 T3 ES2397764 T3 ES 2397764T3
- Authority
- ES
- Spain
- Prior art keywords
- cyclobutyl
- ethyl
- tetrahydroisoquinolin
- chlorophenyl
- oxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 title description 46
- 238000002560 therapeutic procedure Methods 0.000 title description 3
- -1 C3-C12-cycloalkyl Chemical group 0.000 claims abstract description 919
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 122
- 239000001257 hydrogen Substances 0.000 claims abstract description 91
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 91
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 56
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 44
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 29
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 24
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 11
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 10
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims abstract description 10
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 8
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 8
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims abstract description 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 121
- 125000004432 carbon atom Chemical group C* 0.000 claims description 114
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 59
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 57
- 150000003254 radicals Chemical class 0.000 claims description 51
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical group 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 31
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- 201000000980 schizophrenia Diseases 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 9
- SLZRQHPTDIRHGH-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2-(dimethylamino)ethanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCN(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 SLZRQHPTDIRHGH-UHFFFAOYSA-N 0.000 claims description 9
- 208000020016 psychiatric disease Diseases 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
- 208000012902 Nervous system disease Diseases 0.000 claims description 8
- 208000028017 Psychotic disease Diseases 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000000926 neurological effect Effects 0.000 claims description 6
- 150000003456 sulfonamides Chemical class 0.000 claims description 6
- JVWGCNRZGSAAFG-UHFFFAOYSA-N 2-amino-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]ethanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCN)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 JVWGCNRZGSAAFG-UHFFFAOYSA-N 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- 208000019022 Mood disease Diseases 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 230000001149 cognitive effect Effects 0.000 claims description 4
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 4
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
- LZVMIXLKUFZXIB-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-1h-1,2,4-triazole-5-sulfonamide Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCCNS(=O)(=O)C=4NN=CN=4)=CC=C3CCN2)CCC1 LZVMIXLKUFZXIB-UHFFFAOYSA-N 0.000 claims description 4
- OPQOHHWHGHUXEY-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-(ethylamino)propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCNCC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 OPQOHHWHGHUXEY-UHFFFAOYSA-N 0.000 claims description 4
- HNOSPNJMFDPDBU-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 HNOSPNJMFDPDBU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000006799 (C2-C6) alkenylamino group Chemical group 0.000 claims description 3
- MTHWNTDJVALVDC-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-7-methoxy-6-(4-propylsulfonylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CN(S(=O)(=O)CCC)CCN1C(C(=C1)OC)=CC2=C1C(C1(CCC1)C=1C=CC(Cl)=CC=1)NCC2 MTHWNTDJVALVDC-UHFFFAOYSA-N 0.000 claims description 3
- YOOOWVJEFSKIMH-UHFFFAOYSA-N 2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]-1-piperazin-1-ylethanone Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCC(=O)N4CCNCC4)=CC=C3CCN2)CCC1 YOOOWVJEFSKIMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 3
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 3
- JHWDCQIERRBUDY-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2-methylpropanamide Chemical compound C12=CC(OCCNC(=O)C(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 JHWDCQIERRBUDY-UHFFFAOYSA-N 0.000 claims description 3
- JJKBINGTQKJVAP-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-(diethylamino)propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCN(CC)CC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 JJKBINGTQKJVAP-UHFFFAOYSA-N 0.000 claims description 3
- SPFYOJRFXFKILJ-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]methanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 SPFYOJRFXFKILJ-UHFFFAOYSA-N 0.000 claims description 3
- GLTAZTRYJJNQNH-UHFFFAOYSA-N n-[2-[[1-[1-(4-fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCNC1C1(C=2C=CC(F)=CC=2)CCC1 GLTAZTRYJJNQNH-UHFFFAOYSA-N 0.000 claims description 3
- NRWXBSIRGDZNFE-UHFFFAOYSA-N n-[2-[[1-[1-(4-fluorophenyl)cyclobutyl]-2-(1h-imidazol-2-yl)-3,4-dihydro-1h-isoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCN(C=2NC=CN=2)C1C1(C=2C=CC(F)=CC=2)CCC1 NRWXBSIRGDZNFE-UHFFFAOYSA-N 0.000 claims description 3
- VZGOWKZLCTUZQY-UHFFFAOYSA-N n-[2-[[1-[1-(4-fluorophenyl)cyclobutyl]-2-nitroso-3,4-dihydro-1h-isoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCN(N=O)C1C1(C=2C=CC(F)=CC=2)CCC1 VZGOWKZLCTUZQY-UHFFFAOYSA-N 0.000 claims description 3
- QOLRNMNOSZZUEI-UHFFFAOYSA-N n-[2-[[1-[1-(6-chloropyridin-2-yl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCNC1C1(C=2N=C(Cl)C=CC=2)CCC1 QOLRNMNOSZZUEI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- KFMUCGDBJLAYBX-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-7-(4-ethylsulfonylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CN(S(=O)(=O)CC)CCN1C1=CC=C(CCNC2C3(CCC3)C=3C=CC(Cl)=CC=3)C2=C1 KFMUCGDBJLAYBX-UHFFFAOYSA-N 0.000 claims description 2
- SPIZQDOFMLJABW-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-7-[2-(propylsulfonylamino)ethoxy]-3,4-dihydro-1h-isoquinoline-2-carboximidamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCN(C(N)=N)C1C1(C=2C=CC(Cl)=CC=2)CCC1 SPIZQDOFMLJABW-UHFFFAOYSA-N 0.000 claims description 2
- JVWGCNRZGSAAFG-JOCHJYFZSA-N 2-amino-n-[2-[[(1s)-1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]ethanesulfonamide Chemical compound C=1C=C(Cl)C=CC=1C1([C@@H]2NCCC3=CC=C(C=C32)OCCNS(=O)(=O)CCN)CCC1 JVWGCNRZGSAAFG-JOCHJYFZSA-N 0.000 claims description 2
- SOUICFBHPNOJOX-UHFFFAOYSA-N 2-amino-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-1,3-thiazole-5-sulfonamide Chemical compound S1C(N)=NC=C1S(=O)(=O)NCCOC1=CC=C(CCNC2C3(CCC3)C=3C=CC(Cl)=CC=3)C2=C1 SOUICFBHPNOJOX-UHFFFAOYSA-N 0.000 claims description 2
- SCHHYAJELTZZQH-UHFFFAOYSA-N 3-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]-n-(2-methoxyethyl)propane-1-sulfonamide Chemical compound C12=CC(OCCCS(=O)(=O)NCCOC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 SCHHYAJELTZZQH-UHFFFAOYSA-N 0.000 claims description 2
- RNVUOYZLPFCBTM-UHFFFAOYSA-N 3-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]-n-(2-methoxyphenyl)propane-1-sulfonamide Chemical compound COC1=CC=CC=C1NS(=O)(=O)CCCOC1=CC=C(CCNC2C3(CCC3)C=3C=CC(Cl)=CC=3)C2=C1 RNVUOYZLPFCBTM-UHFFFAOYSA-N 0.000 claims description 2
- YGMISHUULIENHT-UHFFFAOYSA-N 3-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]-n-[2-(dimethylamino)ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCCS(=O)(=O)NCCN(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 YGMISHUULIENHT-UHFFFAOYSA-N 0.000 claims description 2
- YDMSLYDNNSQKRL-UHFFFAOYSA-N 3-amino-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-1h-1,2,4-triazole-5-sulfonamide Chemical compound NC1=NNC(S(=O)(=O)NCCOC=2C=C3C(NCCC3=CC=2)C2(CCC2)C=2C=CC(Cl)=CC=2)=N1 YDMSLYDNNSQKRL-UHFFFAOYSA-N 0.000 claims description 2
- HPBAGPWCEQUCCH-UHFFFAOYSA-N 3-amino-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]benzenesulfonamide Chemical compound NC1=CC=CC(S(=O)(=O)NCCOC=2C=C3C(NCCC3=CC=2)C2(CCC2)C=2C=CC(Cl)=CC=2)=C1 HPBAGPWCEQUCCH-UHFFFAOYSA-N 0.000 claims description 2
- WTHUCCPRLQPPRP-UHFFFAOYSA-N 4-amino-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]benzenesulfonamide Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NCCOC1=CC=C(CCNC2C3(CCC3)C=3C=CC(Cl)=CC=3)C2=C1 WTHUCCPRLQPPRP-UHFFFAOYSA-N 0.000 claims description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 2
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 2
- RTZMOJNFHOLHID-UHFFFAOYSA-N n-(2-aminoethyl)-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCN(CCN)S(=O)(=O)CCC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 RTZMOJNFHOLHID-UHFFFAOYSA-N 0.000 claims description 2
- UTGREPLRQLKDPU-UHFFFAOYSA-N n-(3-aminopropyl)-3-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]propane-1-sulfonamide Chemical compound C12=CC(OCCCS(=O)(=O)NCCCN)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 UTGREPLRQLKDPU-UHFFFAOYSA-N 0.000 claims description 2
- QEFFFKMKMYWHRR-UHFFFAOYSA-N n-[2-[[1-[1-(3-amino-4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCNC1C1(C=2C=C(N)C(Cl)=CC=2)CCC1 QEFFFKMKMYWHRR-UHFFFAOYSA-N 0.000 claims description 2
- MTUAQIULLPZYJI-UHFFFAOYSA-N n-[2-[[1-[1-(3-chlorophenyl)cyclobutyl]-2-(cyanomethyl)-3,4-dihydro-1h-isoquinolin-7-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCN(CC#N)C1C1(C=2C=C(Cl)C=CC=2)CCC1 MTUAQIULLPZYJI-UHFFFAOYSA-N 0.000 claims description 2
- DFMIIGKMLKYKHS-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-1,1,1-trifluoromethanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)C(F)(F)F)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 DFMIIGKMLKYKHS-UHFFFAOYSA-N 0.000 claims description 2
- TXJOGYWXAOFQPJ-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2,2-dimethylpropane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CC(C)(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 TXJOGYWXAOFQPJ-UHFFFAOYSA-N 0.000 claims description 2
- PWYASOVTWYAJMU-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2-(propan-2-ylamino)ethanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCNC(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 PWYASOVTWYAJMU-UHFFFAOYSA-N 0.000 claims description 2
- DPSWMYZHSBERSV-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2-hydroxyethanesulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCO)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 DPSWMYZHSBERSV-UHFFFAOYSA-N 0.000 claims description 2
- IYOCVWKMKBXMFB-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-2-methoxybenzenesulfonamide Chemical compound COC1=CC=CC=C1S(=O)(=O)NCCOC1=CC=C(CCNC2C3(CCC3)C=3C=CC(Cl)=CC=3)C2=C1 IYOCVWKMKBXMFB-UHFFFAOYSA-N 0.000 claims description 2
- BXIQGPFTDXRFPO-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3,3,3-trifluoropropane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC(F)(F)F)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 BXIQGPFTDXRFPO-UHFFFAOYSA-N 0.000 claims description 2
- DIKJJDYLJPVLBA-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-(dimethylamino)propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCN(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 DIKJJDYLJPVLBA-UHFFFAOYSA-N 0.000 claims description 2
- NWKFACUOXCQDLQ-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-(methylamino)propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCNC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 NWKFACUOXCQDLQ-UHFFFAOYSA-N 0.000 claims description 2
- KFLPSIMSFHENAV-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-(propylamino)propane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCNCCC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 KFLPSIMSFHENAV-UHFFFAOYSA-N 0.000 claims description 2
- CZHDXPQPFJGSLH-UHFFFAOYSA-N n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-fluoropropane-1-sulfonamide Chemical compound C12=CC(OCCNS(=O)(=O)CCCF)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 CZHDXPQPFJGSLH-UHFFFAOYSA-N 0.000 claims description 2
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- XHPCAKHRCINLQY-UHFFFAOYSA-N n-[2-[[5-bromo-1-[1-(4-fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-8-yl]oxy]ethyl]propane-1-sulfonamide Chemical compound C1=2C(OCCNS(=O)(=O)CCC)=CC=C(Br)C=2CCNC1C1(C=2C=CC(F)=CC=2)CCC1 XHPCAKHRCINLQY-UHFFFAOYSA-N 0.000 claims description 2
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- RGMINFZJHGBKLN-UHFFFAOYSA-N n-[6-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]pyridin-3-yl]pyridine-3-sulfonamide Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OC=4N=CC(NS(=O)(=O)C=5C=NC=CC=5)=CC=4)=CC=C3CCN2)CCC1 RGMINFZJHGBKLN-UHFFFAOYSA-N 0.000 claims description 2
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- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
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- NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 claims 2
- ICDHRPUTNJRICH-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-7-(3-piperazin-1-ylsulfonylpropoxy)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCCCS(=O)(=O)N4CCNCC4)=CC=C3CCN2)CCC1 ICDHRPUTNJRICH-UHFFFAOYSA-N 0.000 claims 1
- RJXSBXRBUSIOSP-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-7-methoxy-2-propylsulfonyl-6-(4-propylsulfonylpiperazin-1-yl)-3,4-dihydro-1h-isoquinoline Chemical compound C1CN(S(=O)(=O)CCC)CCN1C(C(=C1)OC)=CC2=C1C(C1(CCC1)C=1C=CC(Cl)=CC=1)N(S(=O)(=O)CCC)CC2 RJXSBXRBUSIOSP-UHFFFAOYSA-N 0.000 claims 1
- IUOSBWBYPZVTEC-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-n'-cyano-7-[2-(propylsulfonylamino)ethoxy]-3,4-dihydro-1h-isoquinoline-2-carboximidamide Chemical compound C12=CC(OCCNS(=O)(=O)CCC)=CC=C2CCN(C(=N)NC#N)C1C1(C=2C=CC(Cl)=CC=2)CCC1 IUOSBWBYPZVTEC-UHFFFAOYSA-N 0.000 claims 1
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- SBKFEBMEQZZIEW-UHFFFAOYSA-N 1-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]-3-propan-2-ylurea Chemical compound C12=CC(OCCNC(=O)NC(C)C)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 SBKFEBMEQZZIEW-UHFFFAOYSA-N 0.000 claims 1
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- ONSIMIIELDCPCL-UHFFFAOYSA-N 3-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]-n-propylpropane-1-sulfonamide Chemical compound C12=CC(OCCCS(=O)(=O)NCCC)=CC=C2CCNC1C1(C=2C=CC(Cl)=CC=2)CCC1 ONSIMIIELDCPCL-UHFFFAOYSA-N 0.000 claims 1
- WALPPLJUPQTGIH-UHFFFAOYSA-N 3-chloro-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCCNS(=O)(=O)C=4C=C(Cl)C=CC=4)=CC=C3CCN2)CCC1 WALPPLJUPQTGIH-UHFFFAOYSA-N 0.000 claims 1
- SNSSOOWZWMKUDH-UHFFFAOYSA-N 4-chloro-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCCNS(=O)(=O)C=4C=CC(Cl)=CC=4)=CC=C3CCN2)CCC1 SNSSOOWZWMKUDH-UHFFFAOYSA-N 0.000 claims 1
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- CDKYEKSHRQNZBA-UHFFFAOYSA-N 6-chloro-n-[2-[[1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]pyridine-3-sulfonamide Chemical compound C1=CC(Cl)=CC=C1C1(C2C3=CC(OCCNS(=O)(=O)C=4C=NC(Cl)=CC=4)=CC=C3CCN2)CCC1 CDKYEKSHRQNZBA-UHFFFAOYSA-N 0.000 claims 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 1
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- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
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- OYIDADXRZPYNCD-RUZDIDTESA-N n-[2-[[(1s)-1-[1-(4-chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy]ethyl]pyridine-3-sulfonamide Chemical compound C1=CC(Cl)=CC=C1C1([C@H]2C3=CC(OCCNS(=O)(=O)C=4C=NC=CC=4)=CC=C3CCN2)CCC1 OYIDADXRZPYNCD-RUZDIDTESA-N 0.000 claims 1
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- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- VSFLTFOAYLACBX-UHFFFAOYSA-N propane-1-sulfonamide;hydrochloride Chemical compound Cl.CCCS(N)(=O)=O VSFLTFOAYLACBX-UHFFFAOYSA-N 0.000 description 1
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
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- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JQJOGAGLBDBMLU-UHFFFAOYSA-N pyridine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=N1 JQJOGAGLBDBMLU-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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- 238000011160 research Methods 0.000 description 1
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- 238000007363 ring formation reaction Methods 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
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- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
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- 208000011580 syndromic disease Diseases 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- XNZHARUPDNUSOJ-UHFFFAOYSA-N tert-butyl 1-(1-pyridin-2-ylcyclobutyl)-7-(trifluoromethylsulfonyloxy)-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC2=CC=C(OS(=O)(=O)C(F)(F)F)C=C2C1C1(C=2N=CC=CC=2)CCC1 XNZHARUPDNUSOJ-UHFFFAOYSA-N 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
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- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
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- 125000001544 thienyl group Chemical group 0.000 description 1
- 208000016686 tic disease Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4131308P | 2008-04-01 | 2008-04-01 | |
| US41313P | 2008-04-01 | ||
| PCT/EP2009/053800 WO2009121872A2 (en) | 2008-04-01 | 2009-03-31 | Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2397764T3 true ES2397764T3 (es) | 2013-03-11 |
Family
ID=40687932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09727055T Active ES2397764T3 (es) | 2008-04-01 | 2009-03-31 | Tetrahidroisoquinolinas, composiciones farmacéuticas que las contienen, y su uso en terapia |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8653100B2 (enExample) |
| EP (2) | EP2527328A1 (enExample) |
| JP (1) | JP5554319B2 (enExample) |
| CN (2) | CN102083797B (enExample) |
| CA (1) | CA2720004A1 (enExample) |
| ES (1) | ES2397764T3 (enExample) |
| MX (1) | MX2010010773A (enExample) |
| WO (1) | WO2009121872A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2527328A1 (en) | 2008-04-01 | 2012-11-28 | Abbott GmbH & Co. KG | Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy |
| AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
| TW201038569A (en) * | 2009-02-16 | 2010-11-01 | Abbott Gmbh & Co Kg | Heterocyclic compounds, pharmaceutical compositions containing them, and their use in therapy |
| US8877794B2 (en) * | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9045459B2 (en) | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9309200B2 (en) * | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| CN103889968A (zh) * | 2011-08-05 | 2014-06-25 | 艾伯维德国有限责任两合公司 | 氨基苯并二氢吡喃、氨基苯并二氢噻喃及氨基-1,2,3,4-四氢喹啉衍生物,包含这些化合物的药用组合物,及其在治疗中的用途 |
| MX2014006004A (es) | 2011-11-18 | 2015-04-16 | Abbvie Deutschland | Derivados de aminobenzociclohepteno, aminotetralina, aminoindano y fenalcilamina n-sustituidas, composiciones farmaceuticas que los contienen, y su uso en terapia. |
| US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9656955B2 (en) | 2013-03-15 | 2017-05-23 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9650334B2 (en) | 2013-03-15 | 2017-05-16 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| JP2016537323A (ja) | 2013-10-17 | 2016-12-01 | アッヴィ・ドイチュラント・ゲー・エム・ベー・ハー・ウント・コー・カー・ゲー | アミノクロマン誘導体、アミノチオクロマン誘導体およびアミノ−1,2,3,4−テトラヒドロキノリン誘導体、これらを含有する医薬組成物、および治療におけるこれらの使用 |
| AU2014336154A1 (en) | 2013-10-17 | 2016-04-28 | AbbVie Deutschland GmbH & Co. KG | Aminotetraline and aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9550754B2 (en) | 2014-09-11 | 2017-01-24 | AbbVie Deutschland GmbH & Co. KG | 4,5-dihydropyrazole derivatives, pharmaceutical compositions containing them, and their use in therapy |
| CN105130893B (zh) * | 2015-09-08 | 2018-04-10 | 大连理工大学 | 一种1‑苄基‑6‑甲氧羰甲基四氢异喹啉衍生物、制备方法及其抗血小板聚集的应用 |
| CN108884050B (zh) * | 2016-04-13 | 2022-07-05 | Ucb生物制药私人有限公司 | 四氢异喹啉衍生物 |
| CN114957049B (zh) * | 2022-06-13 | 2023-10-03 | 河北冠龙农化有限公司 | 一种n-苯基-n-三氯甲硫基苯磺酰胺的合成方法 |
Family Cites Families (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8004002L (sv) | 1980-05-29 | 1981-11-30 | Arvidsson Folke Lars Erik | Terapeutiskt anvendbara tetralinderivat |
| EP0091241B1 (en) | 1982-04-02 | 1988-12-28 | Takeda Chemical Industries, Ltd. | Condensed pyrrolinone derivatives, and their production |
| US4789678A (en) | 1986-08-25 | 1988-12-06 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing α-alkyl-4-amino-3-quinolinemethanols and 1-(4-aralkylamino-3-quinolinyl)alkanones and related compounds |
| US4927838A (en) | 1987-07-10 | 1990-05-22 | Hoffman-La Roche Inc. | Pyridine compounds which are useful in treating a disease state characterized by an excess of platelet activating factors |
| ZA885824B (en) | 1987-08-14 | 1989-04-26 | Merrell Dow Pharma | Novel antidepressants |
| US5300523A (en) | 1988-07-28 | 1994-04-05 | Bayer Aktiengesellschaft | Substituted aminomethyltetralins and their heterocyclic analogues |
| US5545755A (en) | 1989-05-31 | 1996-08-13 | The Upjohn Company | Therapeutically useful 2-aminotetralin derivatives |
| CA2051399C (en) | 1989-05-31 | 2003-12-30 | Chiu-Hong Lin | Therapeutically useful 2-aminotetralin derivatives |
| WO1992006967A1 (en) | 1990-10-12 | 1992-04-30 | The Upjohn Company | Therapeutically useful 2-aminotetralin derivatives |
| US5071875A (en) | 1989-09-25 | 1991-12-10 | Northwestern University | Substituted 2-amidotetralins as melatonin agonists and antagonists |
| CA2106197A1 (en) | 1991-04-26 | 1992-10-27 | Montford F. Piercey | Method of treating/preventing substance abuse |
| JPH05213884A (ja) | 1991-06-14 | 1993-08-24 | Upjohn Co:The | 新規な4−アミノキノリン類およびこれを有効成分とする高血圧・鬱血性心不全の予防・治療剤 |
| GB9127306D0 (en) | 1991-12-23 | 1992-02-19 | Boots Co Plc | Therapeutic agents |
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| PT1019385E (pt) | 1995-09-15 | 2004-06-30 | Upjohn Co | N-oxidos de aminoaril-oxazolidinona |
| GB9523462D0 (en) * | 1995-11-16 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
| CA2619901A1 (en) | 1996-05-31 | 1997-12-04 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| US6083986A (en) | 1996-07-26 | 2000-07-04 | Icagen, Inc. | Potassium channel inhibitors |
| US6057357A (en) | 1997-04-30 | 2000-05-02 | Warner-Lambert Company | Peripherally selective kappa opioid agonists |
| WO1998056757A1 (fr) | 1997-06-11 | 1998-12-17 | Sankyo Company, Limited | Derives de benzylamine |
| US6060491A (en) | 1997-06-19 | 2000-05-09 | Dupont Pharmaceuticals | 6-membered aromatics as factor Xa inhibitors |
| US20030220234A1 (en) | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
| NZ510988A (en) | 1998-10-07 | 2005-01-28 | Ortho Mcneil Pharm Inc | N-aralkylaminotetralins useful as ligands for the neuropeptide Y5 receptor |
| EP1557168B1 (en) | 1999-07-26 | 2011-11-16 | Msd K.K. | Biarylurea Derivatives |
| ES2250170T3 (es) | 1999-07-28 | 2006-04-16 | Ortho-Mcneil Pharmaceutical, Inc. | Derivados de aminas y de amidas utilizados como ligando para el receptor y5 del neuropeptido y, util en el tratamiento de la obesidad y otros trantornos. |
| GB9918037D0 (en) | 1999-07-30 | 1999-09-29 | Biochemie Gmbh | Organic compounds |
| US6426364B1 (en) | 1999-11-01 | 2002-07-30 | Nps Allelix Corp. | Diaryl-enynes |
| JP4850332B2 (ja) | 2000-10-18 | 2012-01-11 | 東京エレクトロン株式会社 | デュアルダマシン構造のエッチング方法 |
| IL157093A0 (en) * | 2001-03-27 | 2004-02-08 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinolines derivatives as urotensin ii receptor antagonists |
| AU2756602A (en) | 2001-04-25 | 2002-10-31 | Pfizer Products Inc. | Methods and kits for treating depression or preventing deterioration of cognitive function |
| US6831193B2 (en) | 2001-05-18 | 2004-12-14 | Abbott Laboratories | Trisubstituted-N-[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]benzamides which inhibit P2X3 and P2X2/3 containing receptors |
| EP1284257B1 (en) | 2001-08-16 | 2005-10-05 | Pfizer Products Inc. | Difluoromethylene aromatic ethers and their use as inhibitors of the glycine type-1 transporter |
| DE10149370A1 (de) | 2001-10-06 | 2003-04-10 | Merck Patent Gmbh | Pyrazolderivate |
| PT1446387E (pt) | 2001-11-21 | 2009-12-21 | Pharmacia & Upjohn Co Llc | Derivados de aril-1,4-pirazina substituídos |
| DE60219521T2 (de) | 2001-12-20 | 2007-08-16 | H. Lundbeck A/S | Aryloxyphenyl und arylsulfanylphenylderivate |
| GB0130696D0 (en) | 2001-12-21 | 2002-02-06 | Smithkline Beecham Plc | Chemical Compounds |
| DE10210779A1 (de) | 2002-03-12 | 2003-10-09 | Merck Patent Gmbh | Cyclische Amide |
| DE10217006A1 (de) | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| FR2838739B1 (fr) | 2002-04-19 | 2004-05-28 | Sanofi Synthelabo | Derives de n-[phenyl(piperidin-2-yl)methyl)benzamide, leur preparation et leur application en therapeutique |
| WO2003097586A1 (en) | 2002-05-17 | 2003-11-27 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid vr1 receptor |
| WO2004007468A1 (en) | 2002-07-15 | 2004-01-22 | Merck & Co., Inc. | Piperidino pyrimidine dipeptidyl peptidase inhibitors for the treatment of diabetes |
| FR2842805A1 (fr) | 2002-07-29 | 2004-01-30 | Sanofi Synthelabo | Derives de n-[phenyl(piperidin-2-yl)methyl]benzamide,leur preparation et leur application et therapeutique |
| FR2842804B1 (fr) | 2002-07-29 | 2004-09-03 | Sanofi Synthelabo | Derives de n-[phenyl(piperidin-2-yl)methyl]benzamide, leur preparation et leur application en therapeutique |
| US20040152741A1 (en) | 2002-09-09 | 2004-08-05 | Nps Allelix Corporation | Arylglycine derivatives and their use as glycine transport inhibitors |
| US7084154B2 (en) | 2003-02-11 | 2006-08-01 | Pharmacopeia Drug Disclovery, Inc. | 2-(aminomethyl) arylamide analgesics |
| WO2004072034A1 (en) | 2003-02-17 | 2004-08-26 | F. Hoffmann-La Roche Ag | Piperidine-benzenesulfonamide derivatives |
| BRPI0407616A (pt) | 2003-03-07 | 2006-02-14 | Lilly Co Eli | composto, composição farmacêutica, método para bloquear uma combinação de receptor de mu, capa, delta (heterodìmero) deste em mamìferos, método para tratar ou prevenir obesidade e doenças relacionadas, uso de um composto, e método de suprimir o apetite em um paciente em necessidade deste" |
| DE10315570A1 (de) | 2003-04-05 | 2004-10-14 | Merck Patent Gmbh | Triazolderivate |
| KR20060004967A (ko) | 2003-04-30 | 2006-01-16 | 하. 룬트벡 아크티에 셀스카브 | 방향족 옥시페닐 및 방향족 설파닐페닐 유도체 |
| JP2004359633A (ja) | 2003-06-06 | 2004-12-24 | Bayer Cropscience Ag | イソインドリノン誘導体の殺虫剤としての利用 |
| GB0314479D0 (en) | 2003-06-20 | 2003-07-23 | Glaxo Group Ltd | Compounds |
| GB0314476D0 (en) | 2003-06-20 | 2003-07-23 | Glaxo Group Ltd | Compounds |
| GB0314478D0 (en) | 2003-06-20 | 2003-07-23 | Glaxo Group Ltd | Compounds |
| UA85194C2 (ru) | 2003-08-11 | 2009-01-12 | Ф.Хоффманн-Ля Рош Аг | Пиперазины с or-замещенной фенильной группой и их применение как ингибиторов glyt 1 |
| JP4563386B2 (ja) | 2003-09-09 | 2010-10-13 | エフ.ホフマン−ラ ロシュ アーゲー | 精神病の処置のためのグリシン取り込み阻害剤としての1−(2−アミノ−ベンゾール)−ピペラジン誘導体 |
| NZ545613A (en) | 2003-09-09 | 2009-11-27 | Hoffmann La Roche | 1-benzoyl-piperazine derivatives as glycine uptake inhibitors for the treatment of psychoses |
| FR2861073B1 (fr) | 2003-10-17 | 2006-01-06 | Sanofi Synthelabo | Derives de n-[heteroaryl(piperidin-2-yl)methyl]benzamide, leur preparation et leur application en therapeutique |
| FR2861074B1 (fr) | 2003-10-17 | 2006-04-07 | Sanofi Synthelabo | Derives de n-[phenyl(piperidin-2-yl)methyl]benzamide, leur preparation et leur application en therapeutique |
| FR2861071B1 (fr) | 2003-10-17 | 2006-01-06 | Sanofi Synthelabo | Derives de n-[phenyl(alkylpiperidin-2-yl) methyl]benzamide, leur prepartation et leur application en therapeutique |
| FR2861076B1 (fr) | 2003-10-17 | 2006-01-06 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, leur preparation et leur application en therapeutique |
| FR2861070B1 (fr) | 2003-10-17 | 2006-01-06 | Sanofi Synthelabo | Derives de n-[phenyl(pyrrolidin-2-yl)methyl]benzamide et n-[(azepan-2-yl)phenylmethyl]benzamide, leur preparation et leur application en therapeutique |
| JP4490434B2 (ja) | 2003-10-23 | 2010-06-23 | エフ.ホフマン−ラ ロシュ アーゲー | 神経及び神経精神疾患の処置においてGlyT−1阻害剤として使用するためのトリアザ−スピロピペリジン誘導体 |
| US20070105902A1 (en) | 2003-11-12 | 2007-05-10 | Lindsley Craig W | 4-Phenyl piperdine sulfonyl glycine transporter inhibitors |
| GB0326840D0 (en) | 2003-11-18 | 2003-12-24 | Glaxo Group Ltd | Compounds |
| WO2005058885A2 (en) | 2003-12-18 | 2005-06-30 | Glaxo Group Limited | Piperidine derivatives and their use as glycine transporter inhibitors |
| WO2005058317A1 (en) | 2003-12-18 | 2005-06-30 | Glaxo Group Limited | Glycine transporter-1 inhibirors |
| GB0329362D0 (en) | 2003-12-18 | 2004-01-21 | Glaxo Group Ltd | Compounds |
| US7307163B2 (en) | 2004-04-19 | 2007-12-11 | Symed Labs Limited | Process for the preparation of linezolid and related compounds |
| DE102004030099A1 (de) | 2004-06-22 | 2006-01-12 | Grünenthal GmbH | Gesättigte und ungesättigte 3-Pyridyl-benzocycloalkylmethyl-amine als Serotonin- und/oder Noradrenalin-Reuptake-Hemmer und/oder µ-Opioidrezeptor-Modulatoren |
| PL1768967T3 (pl) | 2004-07-20 | 2009-09-30 | Symed Labs Ltd | Nowe związki pośrednie do wytwarzania linezolidu oraz związki pokrewne |
| WO2006025308A1 (ja) | 2004-08-31 | 2006-03-09 | Matsushita Electric Industrial Co., Ltd. | コンテンツ購入処理端末とその方法、及びプログラム |
| US20060074105A1 (en) | 2004-09-20 | 2006-04-06 | Serenex, Inc. | Substituted quinoline and quinazoline inhibitors of quinone reductase 2 |
| US7511013B2 (en) | 2004-09-29 | 2009-03-31 | Amr Technology, Inc. | Cyclosporin analogues and their pharmaceutical uses |
| MX2007006896A (es) | 2004-12-15 | 2007-06-26 | Hoffmann La Roche | Fenil-metanonas bi- y triciclicas sustituidas como inhibidores del transportador 1 de glicina (glyt-1) para el tratamiento de la enfermedad de alzheimer. |
| SI1848694T1 (sl) | 2005-02-07 | 2010-01-29 | Hoffmann La Roche | Heterocikliäśni substituirani fenil metanoni kot inhibitorji glicinskega transporterja 1 |
| AU2006228957A1 (en) | 2005-04-01 | 2006-10-05 | Methylgene Inc. | Inhibitors of histone deacetylase |
| WO2006121767A2 (en) | 2005-05-06 | 2006-11-16 | Apath, Llc | 4-aminoquinoline compounds for treating virus-related conditions |
| TW200716636A (en) | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| WO2007085899A2 (en) * | 2005-07-06 | 2007-08-02 | Foamix Ltd. | Foamable arthropocidal composition for tropical application |
| US7956050B2 (en) | 2005-07-15 | 2011-06-07 | Albany Molecular Research, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| US7514068B2 (en) | 2005-09-14 | 2009-04-07 | Concert Pharmaceuticals Inc. | Biphenyl-pyrazolecarboxamide compounds |
| WO2007064914A2 (en) | 2005-12-01 | 2007-06-07 | Elan Pharmaceuticals, Inc. | 5-(arylsulfonyl)-pyrazolopiperidines |
| EP2032566A4 (en) | 2006-06-12 | 2009-07-08 | Merck Frosst Canada Ltd | AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME-A-DELTA-9-DESATURASE |
| GB0619176D0 (en) | 2006-09-29 | 2006-11-08 | Lectus Therapeutics Ltd | Ion channel modulators & uses thereof |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| JP5130305B2 (ja) | 2007-02-15 | 2013-01-30 | エフ.ホフマン−ラ ロシュ アーゲー | Taar1リガンドとしての2−アミノオキサゾリン |
| CN101687824A (zh) | 2007-04-19 | 2010-03-31 | 康塞特医药品公司 | 氘化吗啉基化合物 |
| US7531685B2 (en) | 2007-06-01 | 2009-05-12 | Protia, Llc | Deuterium-enriched oxybutynin |
| US8420683B2 (en) | 2007-06-06 | 2013-04-16 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | 5 substituted hydantoins |
| EP2178842A2 (en) | 2007-08-22 | 2010-04-28 | Abbott GmbH & Co. KG | 4-benzylaminoquinolines, pharmaceutical compositions containing them and their use |
| WO2009035598A1 (en) | 2007-09-10 | 2009-03-19 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
| US20090118238A1 (en) | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090088416A1 (en) | 2007-09-26 | 2009-04-02 | Protia, Llc | Deuterium-enriched lapaquistat |
| US20090082471A1 (en) | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| JP2010540635A (ja) | 2007-10-02 | 2010-12-24 | コンサート ファーマシューティカルズ インコーポレイテッド | ピリミジンジオン誘導体 |
| US20090105338A1 (en) | 2007-10-18 | 2009-04-23 | Protia, Llc | Deuterium-enriched gabexate mesylate |
| EP2212298B1 (en) | 2007-10-18 | 2013-03-27 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| WO2009055006A1 (en) | 2007-10-26 | 2009-04-30 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| EP2527328A1 (en) | 2008-04-01 | 2012-11-28 | Abbott GmbH & Co. KG | Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy |
| WO2010020548A1 (en) | 2008-08-20 | 2010-02-25 | F. Hoffmann-La Roche Ag | Glyt1 receptor antagonists |
| AU2009289846B2 (en) | 2008-09-02 | 2014-10-16 | Sanofi-Aventis | Substituted aminoindanes and analogs thereof, and the pharmaceutical use thereof |
| DE102008047162A1 (de) | 2008-09-15 | 2010-03-25 | Institut Für Solarenergieforschung Gmbh | Rückkontaktsolarzelle mit integrierter Bypass-Diode sowie Herstellungsverfahren hierfür |
| TW201038569A (en) | 2009-02-16 | 2010-11-01 | Abbott Gmbh & Co Kg | Heterocyclic compounds, pharmaceutical compositions containing them, and their use in therapy |
| AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
| EP2246331A1 (en) | 2009-04-24 | 2010-11-03 | Westfälische Wilhelms-Universität Münster | NR2B-selective NMDA-receptor antagonists |
| WO2010138901A1 (en) | 2009-05-29 | 2010-12-02 | Biogen Idec Ma Inc | Carboxylic acid-containing compounds, derivatives thereof, and related methods of use |
| US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8877794B2 (en) | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9045459B2 (en) | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9309200B2 (en) | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| CN103889968A (zh) | 2011-08-05 | 2014-06-25 | 艾伯维德国有限责任两合公司 | 氨基苯并二氢吡喃、氨基苯并二氢噻喃及氨基-1,2,3,4-四氢喹啉衍生物,包含这些化合物的药用组合物,及其在治疗中的用途 |
| MX2014006004A (es) | 2011-11-18 | 2015-04-16 | Abbvie Deutschland | Derivados de aminobenzociclohepteno, aminotetralina, aminoindano y fenalcilamina n-sustituidas, composiciones farmaceuticas que los contienen, y su uso en terapia. |
| US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
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| US20110105502A1 (en) | 2011-05-05 |
| US20130203749A1 (en) | 2013-08-08 |
| US8957089B2 (en) | 2015-02-17 |
| CN103224487A (zh) | 2013-07-31 |
| WO2009121872A3 (en) | 2010-01-14 |
| CN102083797B (zh) | 2014-06-04 |
| CA2720004A1 (en) | 2009-10-08 |
| US8653100B2 (en) | 2014-02-18 |
| EP2271625A2 (en) | 2011-01-12 |
| CN102083797A (zh) | 2011-06-01 |
| JP5554319B2 (ja) | 2014-07-23 |
| WO2009121872A2 (en) | 2009-10-08 |
| MX2010010773A (es) | 2011-04-11 |
| EP2271625B1 (en) | 2012-09-12 |
| EP2527328A1 (en) | 2012-11-28 |
| JP2011517453A (ja) | 2011-06-09 |
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