CA2679346A1 - Tricyclic isoquinoline derivatives for treatment of obesity - Google Patents
Tricyclic isoquinoline derivatives for treatment of obesity Download PDFInfo
- Publication number
- CA2679346A1 CA2679346A1 CA002679346A CA2679346A CA2679346A1 CA 2679346 A1 CA2679346 A1 CA 2679346A1 CA 002679346 A CA002679346 A CA 002679346A CA 2679346 A CA2679346 A CA 2679346A CA 2679346 A1 CA2679346 A1 CA 2679346A1
- Authority
- CA
- Canada
- Prior art keywords
- azepino
- tetrahydro
- indole
- cndot
- alkyl
- 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.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims description 16
- 208000008589 Obesity Diseases 0.000 title description 8
- 235000020824 obesity Nutrition 0.000 title description 8
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 202
- 238000000034 method Methods 0.000 claims abstract description 79
- 108091005435 5-HT6 receptors Proteins 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- -1 imidazolyl-methyl Chemical group 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 230000037396 body weight Effects 0.000 claims description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 230000009467 reduction Effects 0.000 claims description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 235000019786 weight gain Nutrition 0.000 claims description 8
- GTTLPYDKIIPQQI-UHFFFAOYSA-N 1-(phenylsulfonyl)-1,3,4,5-tetrahydropyrrolo[4,3,2-de]isoquinoline Chemical compound C1=C(C=23)CNCC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 GTTLPYDKIIPQQI-UHFFFAOYSA-N 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000003287 optical effect Effects 0.000 claims description 6
- 239000004031 partial agonist Substances 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- QOEYGXNMQBQLFB-UHFFFAOYSA-N 1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indol Chemical compound C1=C(C=23)CCNCC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 QOEYGXNMQBQLFB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 150000003951 lactams Chemical group 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000003751 serotonin 6 antagonist Substances 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
- QURMAAVIGALLEC-UHFFFAOYSA-N 2-(1-benzothiophen-2-ylsulfonyl)-6-ethyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C1=CC=C2SC(S(=O)(=O)N3C=C4CN(CC=5C=CC=C3C4=5)CC)=CC2=C1 QURMAAVIGALLEC-UHFFFAOYSA-N 0.000 claims description 3
- RSIILEAOAXQJTC-UHFFFAOYSA-N 2-(2-chlorophenyl)sulfonyl-6-ethyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C=12C3=CC=CC=1CN(CC)CC2=CN3S(=O)(=O)C1=CC=CC=C1Cl RSIILEAOAXQJTC-UHFFFAOYSA-N 0.000 claims description 3
- CUGMEDIZNAIZJK-UHFFFAOYSA-N 5-methyl-1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indole Chemical compound C=12C3=CC=CC=1CN(C)CCC2=CN3S(=O)(=O)C1=CC=CC=C1 CUGMEDIZNAIZJK-UHFFFAOYSA-N 0.000 claims description 3
- XUXKRZWBBSHQIA-UHFFFAOYSA-N 6-ethyl-2-(2-methoxy-5-methylphenyl)sulfonyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C=12C3=CC=CC=1CN(CC)CC2=CN3S(=O)(=O)C1=CC(C)=CC=C1OC XUXKRZWBBSHQIA-UHFFFAOYSA-N 0.000 claims description 3
- HDWPPKRQCUSKOL-UHFFFAOYSA-N 6-ethyl-2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C=12C3=CC=CC=1CN(CC)CC2=CN3S(=O)(=O)C1=CC=CC=C1C(F)(F)F HDWPPKRQCUSKOL-UHFFFAOYSA-N 0.000 claims description 3
- WMHLDULSLHZDIB-UHFFFAOYSA-N 6-methyl-1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indol-7-ol Chemical compound C=12C3=CC=C(O)C=1C(C)NCCC2=CN3S(=O)(=O)C1=CC=CC=C1 WMHLDULSLHZDIB-UHFFFAOYSA-N 0.000 claims description 3
- FNTIMKOXGDBGCH-UHFFFAOYSA-N 6-methyl-1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indole Chemical compound C=12C3=CC=CC=1C(C)NCCC2=CN3S(=O)(=O)C1=CC=CC=C1 FNTIMKOXGDBGCH-UHFFFAOYSA-N 0.000 claims description 3
- YZEYJYUAFAMVRK-UHFFFAOYSA-N 7-ethoxy-6-methyl-1-(phenylsulfonyl)-3,4,5,6-tetrahydro-1h-azepino[5,4,3-cd]indole Chemical compound C1=C(C2=3)CCNC(C)C=3C(OCC)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 YZEYJYUAFAMVRK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 2
- SZJYSBMEFOOVOT-UHFFFAOYSA-N 2-(3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-3-ylsulfonyl)-4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 SZJYSBMEFOOVOT-UHFFFAOYSA-N 0.000 claims description 2
- DCFURUACQHQNFI-UHFFFAOYSA-N 2-(benzenesulfonyl)-6-(1H-imidazol-2-ylmethyl)-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C1=C(C=23)CN(CC=4NC=CN=4)CC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 DCFURUACQHQNFI-UHFFFAOYSA-N 0.000 claims description 2
- FPKZCBWYZLWHHN-UHFFFAOYSA-N 2-(benzenesulfonyl)-6-(pyrrolidin-2-ylmethyl)-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C1=C(C=23)CN(CC4NCCC4)CC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 FPKZCBWYZLWHHN-UHFFFAOYSA-N 0.000 claims description 2
- MHBVHFPOTVTIIV-UHFFFAOYSA-N 2-(benzenesulfonyl)-6-(pyrrolidin-3-ylmethyl)-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C1=C(C=23)CN(CC4CNCC4)CC3=CC=CC=2N1S(=O)(=O)C1=CC=CC=C1 MHBVHFPOTVTIIV-UHFFFAOYSA-N 0.000 claims description 2
- IJLNIWAAFNHRMB-UHFFFAOYSA-N 2-(benzenesulfonyl)-6-ethyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C=12C3=CC=CC=1CN(CC)CC2=CN3S(=O)(=O)C1=CC=CC=C1 IJLNIWAAFNHRMB-UHFFFAOYSA-N 0.000 claims description 2
- IDBZXZWHWDELAY-UHFFFAOYSA-N 2-(benzenesulfonyl)-6-methyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene Chemical compound C=12C3=CC=CC=1CN(C)CC2=CN3S(=O)(=O)C1=CC=CC=C1 IDBZXZWHWDELAY-UHFFFAOYSA-N 0.000 claims description 2
- XPCBYLKWDFJZJW-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-6-yl]-N,N-dimethylethanamine Chemical compound C=12C3=CC=CC=1CN(CCN(C)C)CC2=CN3S(=O)(=O)C1=CC=CC=C1 XPCBYLKWDFJZJW-UHFFFAOYSA-N 0.000 claims description 2
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
- OGHLQPHXJWUNCN-UHFFFAOYSA-N 3-(1,2-dimethylimidazol-4-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CN1C(C)=NC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 OGHLQPHXJWUNCN-UHFFFAOYSA-N 0.000 claims description 2
- LHRXWSTUFXVPDK-UHFFFAOYSA-N 3-(1-benzofuran-2-ylsulfonyl)-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1CNCC2=CC=CC3=C2C1=CN3S(=O)(=O)C1=CC2=CC=CC=C2O1 LHRXWSTUFXVPDK-UHFFFAOYSA-N 0.000 claims description 2
- RJVMWHMOILEELU-UHFFFAOYSA-N 3-(1-benzothiophen-2-ylsulfonyl)-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1CNCC2=CC=CC3=C2C1=CN3S(=O)(=O)C1=CC2=CC=CC=C2S1 RJVMWHMOILEELU-UHFFFAOYSA-N 0.000 claims description 2
- ZZOGUNWAOMZEJM-UHFFFAOYSA-N 3-(1-benzothiophen-3-ylsulfonyl)-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1CNCC2=CC=CC3=C2C1=CN3S(=O)(=O)C1=CSC2=CC=CC=C12 ZZOGUNWAOMZEJM-UHFFFAOYSA-N 0.000 claims description 2
- BPBPQSGPSGOITK-UHFFFAOYSA-N 3-(1-methylimidazol-4-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CN1C=NC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 BPBPQSGPSGOITK-UHFFFAOYSA-N 0.000 claims description 2
- VEQKNDHXVMXBPI-UHFFFAOYSA-N 3-(2,4-difluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 VEQKNDHXVMXBPI-UHFFFAOYSA-N 0.000 claims description 2
- DFTKOYUJDUEEOW-UHFFFAOYSA-N 3-(2,5-difluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound FC1=CC=C(F)C(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 DFTKOYUJDUEEOW-UHFFFAOYSA-N 0.000 claims description 2
- UQSLEKLDWURQRH-UHFFFAOYSA-N 3-(2,5-dimethylfuran-3-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound O1C(C)=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1C UQSLEKLDWURQRH-UHFFFAOYSA-N 0.000 claims description 2
- HIDJWWKDCABFIX-UHFFFAOYSA-N 3-(2,5-dimethylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CC1=CC=C(C)C(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 HIDJWWKDCABFIX-UHFFFAOYSA-N 0.000 claims description 2
- VFULUTRECSYTSU-UHFFFAOYSA-N 3-(2,5-dimethylthiophen-3-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound S1C(C)=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1C VFULUTRECSYTSU-UHFFFAOYSA-N 0.000 claims description 2
- XBRWVPYQEFPNMM-UHFFFAOYSA-N 3-(2,6-difluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound FC1=CC=CC(F)=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 XBRWVPYQEFPNMM-UHFFFAOYSA-N 0.000 claims description 2
- KONIGWLFZPECBZ-UHFFFAOYSA-N 3-(2-chloro-6-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CC1=CC=CC(Cl)=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 KONIGWLFZPECBZ-UHFFFAOYSA-N 0.000 claims description 2
- SXCMVHPFIXZXMR-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound ClC1=CC=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 SXCMVHPFIXZXMR-UHFFFAOYSA-N 0.000 claims description 2
- OLTLETMORSQJIZ-UHFFFAOYSA-N 3-(2-ethoxy-5-propan-2-ylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CCOC1=CC=C(C(C)C)C=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 OLTLETMORSQJIZ-UHFFFAOYSA-N 0.000 claims description 2
- JPGKHXYTUDUDDO-UHFFFAOYSA-N 3-(2-methoxy-4-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC(C)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 JPGKHXYTUDUDDO-UHFFFAOYSA-N 0.000 claims description 2
- HDELXLQNDQWJBH-UHFFFAOYSA-N 3-(2-methoxy-5-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC=C(C)C=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 HDELXLQNDQWJBH-UHFFFAOYSA-N 0.000 claims description 2
- IQYOCENNLCSLCS-UHFFFAOYSA-N 3-(2-methoxy-6-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound COC1=CC=CC(C)=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 IQYOCENNLCSLCS-UHFFFAOYSA-N 0.000 claims description 2
- UYLHSQPLYNPOAU-UHFFFAOYSA-N 3-(2-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CC1=CC=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 UYLHSQPLYNPOAU-UHFFFAOYSA-N 0.000 claims description 2
- LGQZNSKGYATOKG-UHFFFAOYSA-N 3-(3,4-difluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1=C(F)C(F)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 LGQZNSKGYATOKG-UHFFFAOYSA-N 0.000 claims description 2
- JRAVWLSYQITGRP-UHFFFAOYSA-N 3-(3,5-difluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound FC1=CC(F)=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 JRAVWLSYQITGRP-UHFFFAOYSA-N 0.000 claims description 2
- HDXZZLXIBGNKHC-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CC1=CC(C)=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 HDXZZLXIBGNKHC-UHFFFAOYSA-N 0.000 claims description 2
- JSRQFOATVDUDKP-UHFFFAOYSA-N 3-(3-chloro-2-methylphenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 JSRQFOATVDUDKP-UHFFFAOYSA-N 0.000 claims description 2
- WFHSFGRMERGQHT-UHFFFAOYSA-N 3-(3-chloro-4-fluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1=C(Cl)C(F)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 WFHSFGRMERGQHT-UHFFFAOYSA-N 0.000 claims description 2
- XYDMEXRIHZGAEP-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound ClC1=CC=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 XYDMEXRIHZGAEP-UHFFFAOYSA-N 0.000 claims description 2
- CIQXLKCGLOJSAU-UHFFFAOYSA-N 3-(3-fluorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound FC1=CC=CC(S(=O)(=O)N2C=3C=CC=C4CNCCC(C=34)=C2)=C1 CIQXLKCGLOJSAU-UHFFFAOYSA-N 0.000 claims description 2
- KSPRIUXWTXZXAY-UHFFFAOYSA-N 3-(4,5-dichlorothiophen-2-yl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound S1C(Cl)=C(Cl)C=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 KSPRIUXWTXZXAY-UHFFFAOYSA-N 0.000 claims description 2
- OTIFSLPNFUCNTN-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=CC=C2CNCC3)=C2C3=C1 OTIFSLPNFUCNTN-UHFFFAOYSA-N 0.000 claims description 2
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- 239000013557 residual solvent Substances 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 238000005055 short column chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- YDBPZCVWPFMBDH-UHFFFAOYSA-N tert-butyl 2-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1C=O YDBPZCVWPFMBDH-UHFFFAOYSA-N 0.000 description 1
- DWLADVOODHZCFV-UHFFFAOYSA-N tert-butyl 3-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)C1 DWLADVOODHZCFV-UHFFFAOYSA-N 0.000 description 1
- DKUWRGCGHQSPCP-UHFFFAOYSA-N tert-butyl 3-oxo-1,3,4,6-tetrahydro-5h-azepino[5,4,3-cd]indole-5-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CC2=CC=CC3=C2C1=CN3 DKUWRGCGHQSPCP-UHFFFAOYSA-N 0.000 description 1
- ZBNZVZUXFNQJFV-UHFFFAOYSA-N tert-butyl 7-(acetyloxy)-6-methyl-1,3,4,6-tetrahydro-5h-azepino[5,4,3-cd]indole-5-carboxylate Chemical compound CC1N(C(=O)OC(C)(C)C)CCC2=CNC3=CC=C(OC(C)=O)C1=C23 ZBNZVZUXFNQJFV-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 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
- 239000003643 water by type Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- 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
-
- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0700611 | 2007-03-13 | ||
| SE0700611-7 | 2007-03-13 | ||
| US202907P | 2007-11-05 | 2007-11-05 | |
| US61/002,029 | 2007-11-05 | ||
| PCT/EP2008/053002 WO2008110598A1 (en) | 2007-03-13 | 2008-03-13 | Tricyclic isoquinoline derivatives for treatment of obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2679346A1 true CA2679346A1 (en) | 2008-09-18 |
Family
ID=39462457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002679346A Abandoned CA2679346A1 (en) | 2007-03-13 | 2008-03-13 | Tricyclic isoquinoline derivatives for treatment of obesity |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8138333B2 (enExample) |
| EP (1) | EP2134714A1 (enExample) |
| JP (1) | JP2010520917A (enExample) |
| CN (1) | CN101631787A (enExample) |
| AU (1) | AU2008225753A1 (enExample) |
| BR (1) | BRPI0808791A2 (enExample) |
| CA (1) | CA2679346A1 (enExample) |
| EA (1) | EA016592B1 (enExample) |
| NZ (1) | NZ579360A (enExample) |
| WO (1) | WO2008110598A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2724449C (en) | 2008-05-29 | 2017-05-30 | Albany Molecular Research, Inc. | 5-ht3 receptor modulators, methods of making, and use thereof |
| EP2575815A4 (en) | 2010-06-04 | 2013-12-25 | Albany Molecular Res Inc | GLYCIN TRANSPORTER 1 INHIBITORS, METHODS OF MAKING THE SAME, AND USES THEREOF |
| WO2012106448A1 (en) * | 2011-02-02 | 2012-08-09 | Biocryst Pharmaceuticals, Inc. | Heterocyclic compounds as janus kinase inhibitors |
| JP6198715B2 (ja) * | 2012-03-06 | 2017-09-20 | 武田薬品工業株式会社 | 三環性化合物 |
| US10675283B2 (en) | 2017-03-24 | 2020-06-09 | University Of South Florida | Compositions and methods for white to beige adipogenesis |
| CN109180687A (zh) * | 2018-08-31 | 2019-01-11 | 山东轩德医药科技有限公司 | 一种瑞卡帕步中间体的制备方法 |
| CN111961047A (zh) * | 2020-08-19 | 2020-11-20 | 南通大学 | 一种6-乙氧基-3,4-二氢-2,7-萘啶-1（2h）-酮及其合成方法 |
| CN115925658B (zh) * | 2022-11-21 | 2024-02-27 | 常州佳德医药科技有限公司 | 一种2-氨基乙基呋喃的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE795451A (fr) * | 1972-02-23 | 1973-08-16 | Pfizer | Agents hypoglycemiants aza indoliques tricycliques |
| US3950343A (en) * | 1973-11-06 | 1976-04-13 | Ayerst, Mckenna And Harrison Ltd. | Pyrroloisoquinoline derivatives |
| MX9700693A (es) | 1994-07-26 | 1997-04-30 | Pfizer | Derivados del 4-indol. |
| US6133287A (en) * | 1998-03-24 | 2000-10-17 | Allelix Biopharmaceuticals Inc. | Piperidine-indole compounds having 5-HT6 affinity |
| GB9820113D0 (en) | 1998-09-15 | 1998-11-11 | Merck Sharp & Dohme | Therapeutic agents |
| MXPA01005905A (es) | 1998-12-11 | 2002-09-18 | Univ Virginia Commonwealth | Ligandos selectivos de receptores de 5-ht6. |
| WO2002032863A1 (en) | 2000-10-20 | 2002-04-25 | Biovitrum Ab | 2-, 3-, 4-, or 5-substituted-n1-(benzensulfonyl)indoles and their use in therapy |
| PL374401A1 (en) * | 2002-06-05 | 2005-10-17 | F.Hoffmann-La Roche Ag | 1-sulfonyl-4-aminoalkoxy indole derivatives as 5-ht6-receptor modulators for the treatment of cns-disorders |
-
2008
- 2008-03-13 BR BRPI0808791A patent/BRPI0808791A2/pt not_active IP Right Cessation
- 2008-03-13 EP EP08717746A patent/EP2134714A1/en not_active Withdrawn
- 2008-03-13 US US12/075,979 patent/US8138333B2/en not_active Expired - Fee Related
- 2008-03-13 JP JP2009553146A patent/JP2010520917A/ja not_active Withdrawn
- 2008-03-13 AU AU2008225753A patent/AU2008225753A1/en not_active Abandoned
- 2008-03-13 WO PCT/EP2008/053002 patent/WO2008110598A1/en not_active Ceased
- 2008-03-13 CN CN200880008061A patent/CN101631787A/zh active Pending
- 2008-03-13 EA EA200970849A patent/EA016592B1/ru not_active IP Right Cessation
- 2008-03-13 CA CA002679346A patent/CA2679346A1/en not_active Abandoned
- 2008-03-13 NZ NZ579360A patent/NZ579360A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN101631787A (zh) | 2010-01-20 |
| US20080293694A1 (en) | 2008-11-27 |
| AU2008225753A1 (en) | 2008-09-18 |
| BRPI0808791A2 (pt) | 2017-05-02 |
| WO2008110598A1 (en) | 2008-09-18 |
| EP2134714A1 (en) | 2009-12-23 |
| EA200970849A1 (ru) | 2010-04-30 |
| JP2010520917A (ja) | 2010-06-17 |
| NZ579360A (en) | 2011-06-30 |
| EA016592B1 (ru) | 2012-06-29 |
| US8138333B2 (en) | 2012-03-20 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20140313 |