ES2397400T3 - 6-arilalquilamino-2,3,4,5-tetrahidro-1H-benzo[D]azepinas como agonistas del receptor 5-HT2C - Google Patents
6-arilalquilamino-2,3,4,5-tetrahidro-1H-benzo[D]azepinas como agonistas del receptor 5-HT2C Download PDFInfo
- Publication number
- ES2397400T3 ES2397400T3 ES06802859T ES06802859T ES2397400T3 ES 2397400 T3 ES2397400 T3 ES 2397400T3 ES 06802859 T ES06802859 T ES 06802859T ES 06802859 T ES06802859 T ES 06802859T ES 2397400 T3 ES2397400 T3 ES 2397400T3
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- Prior art keywords
- alkyl
- optionally substituted
- moiety
- fluorine substituents
- substituents
- Prior art date
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- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 title description 17
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 title description 14
- 239000000018 receptor agonist Substances 0.000 title description 5
- 229940044601 receptor agonist Drugs 0.000 title description 5
- 150000001538 azepines Chemical class 0.000 title description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 488
- 150000001875 compounds Chemical class 0.000 claims abstract description 171
- -1 -SCF3 Chemical group 0.000 claims abstract description 156
- 125000001424 substituent group Chemical group 0.000 claims abstract description 142
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 123
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 67
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 125000005843 halogen group Chemical group 0.000 claims abstract description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 446
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 186
- 239000011737 fluorine Substances 0.000 claims description 104
- 229910052731 fluorine Inorganic materials 0.000 claims description 104
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 102
- 150000003839 salts Chemical class 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 16
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 15
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 12
- 208000019901 Anxiety disease Diseases 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 11
- 230000036506 anxiety Effects 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 235000020824 obesity Nutrition 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
- 208000020401 Depressive disease Diseases 0.000 claims description 3
- NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical group [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 2
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 2
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 2
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 2
- YRJYCMNQWKJLIF-UHFFFAOYSA-N 7-chloro-n-[[4-(3,3-dimethylcyclohexyl)sulfanylphenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound C1C(C)(C)CCCC1SC(C=C1)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 YRJYCMNQWKJLIF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical group C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 3
- NNNTWYJIHRNKLI-UHFFFAOYSA-N 1h-azepine;butanedioic acid Chemical compound N1C=CC=CC=C1.OC(=O)CCC(O)=O NNNTWYJIHRNKLI-UHFFFAOYSA-N 0.000 claims 2
- WXJXADXMDZMENL-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-2-methylcyclopropane-1-carboxamide Chemical compound OC(=O)CCC(O)=O.CC1CC1C(=O)NC(C=C1)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 WXJXADXMDZMENL-UHFFFAOYSA-N 0.000 claims 2
- JGAPDRYDUPAXTC-UHFFFAOYSA-N 4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(cyclopropylmethyl)-1,3-thiazol-2-amine Chemical compound ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CSC=1NCC1CC1 JGAPDRYDUPAXTC-UHFFFAOYSA-N 0.000 claims 1
- PUMAYLVXOKGACW-UHFFFAOYSA-N 7-chloro-n-[[4-(cyclohexylsulfanylmethyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CSC1CCCCC1 PUMAYLVXOKGACW-UHFFFAOYSA-N 0.000 claims 1
- RTPBADGFZLARLC-UHFFFAOYSA-N 7-chloro-n-[[4-(cyclopentylsulfanylmethyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CSC1CCCC1 RTPBADGFZLARLC-UHFFFAOYSA-N 0.000 claims 1
- BMNAANNLKHAPHJ-UHFFFAOYSA-N 7-chloro-n-[[4-(piperidin-1-ylmethyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CN1CCCCC1 BMNAANNLKHAPHJ-UHFFFAOYSA-N 0.000 claims 1
- XFDFQDZUYWLKLH-UHFFFAOYSA-N 7-chloro-n-[[5-(cyclopentylsulfanylmethyl)pyridin-2-yl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound ClC1=CC=C2CCNCCC2=C1NCC(N=C1)=CC=C1CSC1CCCC1 XFDFQDZUYWLKLH-UHFFFAOYSA-N 0.000 claims 1
- TTZFRCXMFRYQPN-UHFFFAOYSA-N 7-chloro-n-[[6-(propan-2-yloxymethyl)pyridin-3-yl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound C1=NC(COC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 TTZFRCXMFRYQPN-UHFFFAOYSA-N 0.000 claims 1
- NCAMZBKDSHETQL-UHFFFAOYSA-N OC(=O)CCC(O)=O.C1=CC(C(=NO)CC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 Chemical compound OC(=O)CCC(O)=O.C1=CC(C(=NO)CC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 NCAMZBKDSHETQL-UHFFFAOYSA-N 0.000 claims 1
- GDXMYHLLNDKCMA-UHFFFAOYSA-N OC(=O)CCC(O)=O.C1=CC(C(C)=NOC)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 Chemical compound OC(=O)CCC(O)=O.C1=CC(C(C)=NOC)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 GDXMYHLLNDKCMA-UHFFFAOYSA-N 0.000 claims 1
- MQOYJCUGWBDBNC-UHFFFAOYSA-N OC(=O)CCC(O)=O.C1CNCCC2=CC=CC=C21 Chemical compound OC(=O)CCC(O)=O.C1CNCCC2=CC=CC=C21 MQOYJCUGWBDBNC-UHFFFAOYSA-N 0.000 claims 1
- TXHNMDXTVJVHIK-UHFFFAOYSA-N butanedioic acid 7-chloro-N-[[4-[N-methoxy-C-(2-methylpropyl)carbonimidoyl]phenyl]methyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(C(CC(C)C)=NOC)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 TXHNMDXTVJVHIK-UHFFFAOYSA-N 0.000 claims 1
- FTODGNHMJAPJSA-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(2,2-dimethylpropyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NCC(C)(C)C)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 FTODGNHMJAPJSA-UHFFFAOYSA-N 0.000 claims 1
- XISZQRCCFSJFBN-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(2-methylpropyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NCC(C)C)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 XISZQRCCFSJFBN-UHFFFAOYSA-N 0.000 claims 1
- HZSNJLHPCXRQEX-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(3,3,3-trifluoropropyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NCCC(F)(F)F)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 HZSNJLHPCXRQEX-UHFFFAOYSA-N 0.000 claims 1
- OJFQUQXQSHXKGD-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(3-methylbutyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NCCC(C)C)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 OJFQUQXQSHXKGD-UHFFFAOYSA-N 0.000 claims 1
- MGUUYMLPYCSKQP-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(cyclopentylmethyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CSC=1NCC1CCCC1 MGUUYMLPYCSKQP-UHFFFAOYSA-N 0.000 claims 1
- QWTCEMOHIDDODE-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(cyclopropylmethyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CSC=1NCC1CC1 QWTCEMOHIDDODE-UHFFFAOYSA-N 0.000 claims 1
- NLHYIOAOCYNANT-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-(cyclopropylmethyl)-5-methyl-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.N=1C(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C(C)SC=1NCC1CC1 NLHYIOAOCYNANT-UHFFFAOYSA-N 0.000 claims 1
- QQZPGFGGDHPUBV-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-ethyl-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NCC)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 QQZPGFGGDHPUBV-UHFFFAOYSA-N 0.000 claims 1
- CJFORJPSXMNXEY-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-methyl-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NC)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 CJFORJPSXMNXEY-UHFFFAOYSA-N 0.000 claims 1
- YVVOPECKZGZIIW-UHFFFAOYSA-N butanedioic acid;4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n-propan-2-yl-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.S1C(NC(C)C)=NC(C=2C=CC(CNC=3C=4CCNCCC=4C=CC=3Cl)=CC=2)=C1 YVVOPECKZGZIIW-UHFFFAOYSA-N 0.000 claims 1
- YCCIVWBBCIZUJC-UHFFFAOYSA-N butanedioic acid;4-[5-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]pyridin-2-yl]-n-(cyclopropylmethyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=N1)=CC=C1C(N=1)=CSC=1NCC1CC1 YCCIVWBBCIZUJC-UHFFFAOYSA-N 0.000 claims 1
- RUXKCAVFVVMXOC-UHFFFAOYSA-N butanedioic acid;4-[6-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]pyridin-3-yl]-n-(cyclopropylmethyl)-1,3-thiazol-2-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(N=C1)=CC=C1C(N=1)=CSC=1NCC1CC1 RUXKCAVFVVMXOC-UHFFFAOYSA-N 0.000 claims 1
- HUKIWWKFJJQDEZ-UHFFFAOYSA-N butanedioic acid;7,7-dichloro-n-[[4-[(2,2,2-trifluoroethylamino)methyl]phenyl]methyl]-1,2,3,4,5,6-hexahydro-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(CNCC(F)(F)F)=CC=C1CNC1C(Cl)(Cl)C=CC2=C1CCNCC2 HUKIWWKFJJQDEZ-UHFFFAOYSA-N 0.000 claims 1
- MHVXCGAJHPZFEK-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[(5-cycloheptyloxypyridin-2-yl)methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(N=C1)=CC=C1OC1CCCCCC1 MHVXCGAJHPZFEK-UHFFFAOYSA-N 0.000 claims 1
- QPYOEBVGVPQMKF-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-(2,2-dimethylpropylsulfonylmethyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(CS(=O)(=O)CC(C)(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 QPYOEBVGVPQMKF-UHFFFAOYSA-N 0.000 claims 1
- VBLFVLISVZYGOI-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-(2-piperidin-1-yl-1,3-thiazol-4-yl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CSC=1N1CCCCC1 VBLFVLISVZYGOI-UHFFFAOYSA-N 0.000 claims 1
- PKCTWOMMLXANLC-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-(n-ethoxy-c-methylcarbonimidoyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(C(C)=NOCC)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 PKCTWOMMLXANLC-UHFFFAOYSA-N 0.000 claims 1
- HVYVTPLDLWESIF-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-(piperidin-1-ylmethyl)phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CN1CCCCC1 HVYVTPLDLWESIF-UHFFFAOYSA-N 0.000 claims 1
- SVFGFADDSFXHHM-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[(2-methylpropylamino)methyl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(CNCC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 SVFGFADDSFXHHM-UHFFFAOYSA-N 0.000 claims 1
- LIYDWRQECHKVPX-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[(cyclohexylamino)methyl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CNC1CCCCC1 LIYDWRQECHKVPX-UHFFFAOYSA-N 0.000 claims 1
- LSXQRKKCGNXRAG-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[(propan-2-ylamino)methyl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(CNC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 LSXQRKKCGNXRAG-UHFFFAOYSA-N 0.000 claims 1
- LXESDNMKFKRXED-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[2-(cyclopropylmethylamino)pyrimidin-4-yl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CC=NC=1NCC1CC1 LXESDNMKFKRXED-UHFFFAOYSA-N 0.000 claims 1
- MKBJYZFIMOFITH-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[4-(cyclopropylmethylamino)pyrimidin-2-yl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=NC=CC=1NCC1CC1 MKBJYZFIMOFITH-UHFFFAOYSA-N 0.000 claims 1
- YHXQRZVDDWABFS-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[6-(cyclopropylmethylamino)pyrimidin-4-yl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=CN=1)=CC=1NCC1CC1 YHXQRZVDDWABFS-UHFFFAOYSA-N 0.000 claims 1
- JLEUWAUXFLMNDN-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[[methyl(propan-2-yl)amino]methyl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(CN(C)C(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 JLEUWAUXFLMNDN-UHFFFAOYSA-N 0.000 claims 1
- SEARHKSIUZINBT-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[4-[c-methyl-n-(2-methylpropoxy)carbonimidoyl]phenyl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.C1=CC(C(C)=NOCC(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 SEARHKSIUZINBT-UHFFFAOYSA-N 0.000 claims 1
- FAAQIPYUYYOMFK-UHFFFAOYSA-N butanedioic acid;7-chloro-n-[[6-(cyclohexylsulfonylmethyl)pyridin-3-yl]methyl]-2,3,4,5-tetrahydro-1h-3-benzazepin-6-amine Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=N1)=CC=C1CS(=O)(=O)C1CCCCC1 FAAQIPYUYYOMFK-UHFFFAOYSA-N 0.000 claims 1
- IRAMRJMRLVJHJJ-UHFFFAOYSA-N butanedioic acid;n-[4-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1C(N=1)=CSC=1NC(=O)C1CC1 IRAMRJMRLVJHJJ-UHFFFAOYSA-N 0.000 claims 1
- BZNXMEIQPYDJEE-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-1-methylcyclopropane-1-carboxamide Chemical compound OC(=O)CCC(O)=O.C=1C=C(CNC=2C=3CCNCCC=3C=CC=2Cl)C=CC=1NC(=O)C1(C)CC1 BZNXMEIQPYDJEE-UHFFFAOYSA-N 0.000 claims 1
- YSZUTHKJBFJCED-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-2,2-dimethylpropanamide Chemical compound OC(=O)CCC(O)=O.C1=CC(NC(=O)C(C)(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 YSZUTHKJBFJCED-UHFFFAOYSA-N 0.000 claims 1
- UEMPZMCYYFKEKZ-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]-n,2,2-trimethylpropanamide Chemical compound OC(=O)CCC(O)=O.C1=CC(N(C(=O)C(C)(C)C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 UEMPZMCYYFKEKZ-UHFFFAOYSA-N 0.000 claims 1
- OHAVTZIPJQHPAA-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]cycloheptanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1NC(=O)C1CCCCCC1 OHAVTZIPJQHPAA-UHFFFAOYSA-N 0.000 claims 1
- BWAUIPVWGRWGQH-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]cyclohexanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1NC(=O)C1CCCCC1 BWAUIPVWGRWGQH-UHFFFAOYSA-N 0.000 claims 1
- ANFFXKOLIJWDDH-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]cyclopentanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1NC(=O)C1CCCC1 ANFFXKOLIJWDDH-UHFFFAOYSA-N 0.000 claims 1
- JWKHCYXJITURHR-UHFFFAOYSA-N butanedioic acid;n-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]cyclopropanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1NC(=O)C1CC1 JWKHCYXJITURHR-UHFFFAOYSA-N 0.000 claims 1
- QAQRCKRELNITQE-UHFFFAOYSA-N butanedioic acid;n-[[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl]methyl]cyclopropanecarboxamide Chemical compound OC(=O)CCC(O)=O.ClC1=CC=C2CCNCCC2=C1NCC(C=C1)=CC=C1CNC(=O)C1CC1 QAQRCKRELNITQE-UHFFFAOYSA-N 0.000 claims 1
- FLLOTTZOXDSJNF-UHFFFAOYSA-N butanedioic acid;s-[4-[[(7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepin-6-yl)amino]methyl]phenyl] n,n-dimethylcarbamothioate Chemical compound OC(=O)CCC(O)=O.C1=CC(SC(=O)N(C)C)=CC=C1CNC1=C(Cl)C=CC2=C1CCNCC2 FLLOTTZOXDSJNF-UHFFFAOYSA-N 0.000 claims 1
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- 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
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- 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
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- 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
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- 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
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Landscapes
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| ES2440483T3 (es) * | 2005-09-01 | 2014-01-29 | Eli Lilly And Company | 2,3,4,5-Tetrahidro-1H-benzo[d]azepinas sustituidas con heterociclo enlazado en 6-N como agonistas del receptor 5-HT2C |
| WO2007132841A1 (ja) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物およびその用途 |
| US7897595B2 (en) | 2006-05-26 | 2011-03-01 | Forest Laboratories Holdings Limited | Pyridoazepine derivatives |
| JP5520051B2 (ja) | 2007-11-15 | 2014-06-11 | 武田薬品工業株式会社 | 縮合ピリジン誘導体およびその用途 |
| JP5216912B2 (ja) | 2008-04-29 | 2013-06-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr1受容体拮抗薬としてのインダゾール化合物 |
| JP5411927B2 (ja) | 2008-05-06 | 2014-02-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr1アンタゴニストとしてのピラゾール化合物 |
| KR20110060904A (ko) | 2008-09-26 | 2011-06-08 | 베링거 인겔하임 인터내셔날 게엠베하 | Ccr1 수용체 길항제로서의 아자인다졸 화합물 |
| RS53130B (sr) | 2009-10-21 | 2014-06-30 | Boehringer Ingelheim International Gmbh | Jedinjenja indazola i pirazolopiridina kao ccr1 receptor antagonisti |
| JP5542214B2 (ja) | 2009-10-27 | 2014-07-09 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr1受容体アンタゴニストとしての複素環化合物 |
| MX2012006524A (es) * | 2009-12-08 | 2012-07-17 | Boehringer Ingelheim Int | Proceso para la sintesis de compuestos intermedios de utilidad para preparar compuestos sustituidos de indazol y azaindol. |
| WO2011137109A1 (en) | 2010-04-30 | 2011-11-03 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as ccr1 receptor antagonists |
| US20130267500A1 (en) | 2010-09-01 | 2013-10-10 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists in the treatment of disorders ameliorated by reduction of norepinephrine level |
| US8546442B2 (en) | 2010-12-23 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Pyrazolopiperidine compounds as CCR1 receptor antagonists |
| US20140206667A1 (en) | 2012-11-14 | 2014-07-24 | Michela Gallagher | Methods and compositions for treating schizophrenia |
| WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| EA201891526A3 (ru) | 2014-07-03 | 2019-05-31 | Селджен Квонтисел Рисёрч, Инк. | Ингибиторы лизин-специфической деметилазы-1 |
| CN105622511B (zh) * | 2014-11-03 | 2018-01-23 | 北京瑞都医药科技有限公司 | 一种减肥药物及其制备方法 |
| CN109071440A (zh) * | 2016-05-13 | 2018-12-21 | 日产化学株式会社 | 2-乙酰基吡啶化合物的制造方法 |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC AGENT FOR URINARY INCONTINENCE OF STRESS AND FECAL INCONTINENCE |
| AU2020416203A1 (en) * | 2020-01-03 | 2022-06-16 | Blue Oak Pharmaceuticals, Inc. | Compounds and compositions for treating CNS disorders |
| CN114163426B (zh) * | 2020-09-10 | 2024-03-19 | 上海爱博医药科技有限公司 | 苯并含氧杂环类化合物及其医药应用 |
| GB202101734D0 (en) | 2021-02-08 | 2021-03-24 | Cerevance Inc | Novel Compounds |
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|---|---|---|---|---|
| US4265890A (en) * | 1978-07-07 | 1981-05-05 | Smithkline Corporation | 6-Phenyl thio- and 6-cyclohexyl thio-2,3,4,5-tetrahydro-1H-3-benzazepines |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| EP0285287A3 (en) | 1987-03-23 | 1990-08-16 | Smithkline Beecham Corporation | 3-benzazepine compounds for use in treating gastrointestinal motility disorders |
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| US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
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| GB9119467D0 (en) | 1991-09-12 | 1991-10-23 | Smithkline Beecham Corp | Chemical compounds |
| US5698766A (en) * | 1995-04-05 | 1997-12-16 | The Regents Of The University Of California | Transgenic animal model for testing drugs for treating eating disorders and epilepsy |
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| SI2332921T1 (sl) | 2003-06-17 | 2016-06-30 | Arena Pharmaceuticals, Inc. | 8-kloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzazapin hidroklorid |
| EA016558B1 (ru) | 2003-06-17 | 2012-05-30 | Арена Фармасьютикалз, Инк. | Производные бензазепина, используемые для лечения заболеваний, ассоциированных с 5-ht-рецептором |
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| WO2007028131A1 (en) * | 2005-09-01 | 2007-03-08 | Eli Lilly And Company | 6-SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-BENZO[d]AZEPINES AS 5-HT2C RECEPTOR AGONISTS |
-
2006
- 2006-09-01 PT PT68028596T patent/PT1924561E/pt unknown
- 2006-09-01 ES ES06802859T patent/ES2397400T3/es active Active
- 2006-09-01 BR BRPI0615048-9A patent/BRPI0615048A2/pt not_active IP Right Cessation
- 2006-09-01 PL PL06802859T patent/PL1924561T3/pl unknown
- 2006-09-01 DK DK06802859.6T patent/DK1924561T3/da active
- 2006-09-01 JP JP2008529336A patent/JP5155864B2/ja not_active Expired - Fee Related
- 2006-09-01 CA CA2619448A patent/CA2619448C/en not_active Expired - Fee Related
- 2006-09-01 EP EP06802859A patent/EP1924561B1/en not_active Not-in-force
- 2006-09-01 AU AU2006287202A patent/AU2006287202B2/en not_active Ceased
- 2006-09-01 WO PCT/US2006/034335 patent/WO2007028083A2/en not_active Ceased
- 2006-09-01 CN CN2006800322352A patent/CN101258131B/zh not_active Expired - Fee Related
- 2006-09-01 US US11/996,751 patent/US20080269196A1/en not_active Abandoned
- 2006-09-01 SI SI200631496T patent/SI1924561T1/sl unknown
-
2011
- 2011-06-09 US US13/156,575 patent/US8680091B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006287202A8 (en) | 2008-03-13 |
| JP5155864B2 (ja) | 2013-03-06 |
| SI1924561T1 (sl) | 2013-02-28 |
| DK1924561T3 (da) | 2012-12-10 |
| PT1924561E (pt) | 2013-01-16 |
| US20110269745A1 (en) | 2011-11-03 |
| BRPI0615048A2 (pt) | 2010-03-30 |
| JP2009507034A (ja) | 2009-02-19 |
| AU2006287202A1 (en) | 2007-03-08 |
| CN101258131B (zh) | 2013-07-24 |
| CN101258131A (zh) | 2008-09-03 |
| WO2007028083A2 (en) | 2007-03-08 |
| EP1924561B1 (en) | 2012-11-14 |
| CA2619448C (en) | 2013-08-13 |
| US20080269196A1 (en) | 2008-10-30 |
| AU2006287202B2 (en) | 2013-01-24 |
| PL1924561T3 (pl) | 2013-03-29 |
| US8680091B2 (en) | 2014-03-25 |
| WO2007028083A3 (en) | 2007-05-18 |
| CA2619448A1 (en) | 2007-03-08 |
| EP1924561A2 (en) | 2008-05-28 |
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