ZA200303697B - Novel benzazepines and related heterocyclic derivatives which are useful as orexin receptor antagonists. - Google Patents
Novel benzazepines and related heterocyclic derivatives which are useful as orexin receptor antagonists. Download PDFInfo
- Publication number
- ZA200303697B ZA200303697B ZA200303697A ZA200303697A ZA200303697B ZA 200303697 B ZA200303697 B ZA 200303697B ZA 200303697 A ZA200303697 A ZA 200303697A ZA 200303697 A ZA200303697 A ZA 200303697A ZA 200303697 B ZA200303697 B ZA 200303697B
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- ZA
- South Africa
- Prior art keywords
- dimethoxy
- benzyl
- benzo
- tetrahydro
- acetamide
- Prior art date
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- 125000000623 heterocyclic group Chemical group 0.000 title claims description 41
- 150000008038 benzoazepines Chemical class 0.000 title description 8
- 229940123730 Orexin receptor antagonist Drugs 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- 150000001875 compounds Chemical class 0.000 claims description 52
- 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 claims description 50
- 125000003342 alkenyl group Chemical group 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 44
- -1 for example Chemical class 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000006193 alkinyl group Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 102000002512 Orexin Human genes 0.000 claims description 18
- 108060005714 orexin Proteins 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 9
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- 239000005557 antagonist Substances 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 208000019116 sleep disease Diseases 0.000 claims description 9
- 102000008834 Orexin receptor Human genes 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 101000598921 Homo sapiens Orexin Proteins 0.000 claims description 5
- MGFOWTAWOHTRRC-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-(2,2,2-trifluoroethyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCC(F)(F)F)C1=CC=CC=C1 MGFOWTAWOHTRRC-UHFFFAOYSA-N 0.000 claims description 4
- UDQSXTNTGLMCLG-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-(pyridin-3-ylmethyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=CN=C1 UDQSXTNTGLMCLG-UHFFFAOYSA-N 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- MBTRBDRYULFSCA-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(OCO2)C2=C1 MBTRBDRYULFSCA-UHFFFAOYSA-N 0.000 claims description 4
- MEFSKYLTPHEZTC-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-2-[8-(2,2-difluoroethoxy)-1-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OCC(F)F)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(OCO2)C2=C1 MEFSKYLTPHEZTC-UHFFFAOYSA-N 0.000 claims description 4
- HKQKTAMBBMTGDD-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1CC(=O)NC1C2=CC=CC=C2CC1 HKQKTAMBBMTGDD-UHFFFAOYSA-N 0.000 claims description 4
- FDPVMURZMWRLLZ-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[5-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-3,5-dihydro-2h-1,4-benzoxazepin-4-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2OCCN1CC(=O)NC1C2=CC=CC=C2CC1 FDPVMURZMWRLLZ-UHFFFAOYSA-N 0.000 claims description 4
- MPFLOPTYHIWHPE-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-(quinolin-2-ylmethyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(C=CC=C2)C2=N1 MPFLOPTYHIWHPE-UHFFFAOYSA-N 0.000 claims description 3
- BNUAZZNLMVATQP-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-prop-2-ynylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCC#C)C1=CC=CC=C1 BNUAZZNLMVATQP-UHFFFAOYSA-N 0.000 claims description 3
- PFLIAQVOGBTBIA-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(2-methylsulfanylethyl)-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCCSC)C1=CC=CC=C1 PFLIAQVOGBTBIA-UHFFFAOYSA-N 0.000 claims description 3
- VFPDOAWGQFDMGO-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-[(1-methylindol-3-yl)methyl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CN(C)C2=CC=CC=C12 VFPDOAWGQFDMGO-UHFFFAOYSA-N 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- KUSBLETVJOWRFU-UHFFFAOYSA-N methyl 3-[[2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetyl]amino]propanoate Chemical compound C=1C=CC=CC=1C(C(=O)NCCC(=O)OC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 KUSBLETVJOWRFU-UHFFFAOYSA-N 0.000 claims description 3
- PSFDFKUZCKOKPS-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-8-propan-2-yloxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC(C)C)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(OCO2)C2=C1 PSFDFKUZCKOKPS-UHFFFAOYSA-N 0.000 claims description 3
- AUSIRTHKKMAJTI-UHFFFAOYSA-N n-(1h-benzimidazol-2-ylmethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=NC2=CC=CC=C2N1 AUSIRTHKKMAJTI-UHFFFAOYSA-N 0.000 claims description 3
- IEJBBQOKWBSLJA-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-8-propoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1CC2=CC=CC=C2C1NC(=O)CN1CCCC=2C=C(OC)C(OCCC)=CC=2C1CC1=CC=C(OC)C(OC)=C1 IEJBBQOKWBSLJA-UHFFFAOYSA-N 0.000 claims description 3
- XPPDSIAZTIOSRT-UHFFFAOYSA-N n-butyl-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)NCCCC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 XPPDSIAZTIOSRT-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- ZDGREJASPPCBKV-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-(pyrazin-2-ylmethyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CN=CC=N1 ZDGREJASPPCBKV-UHFFFAOYSA-N 0.000 claims description 2
- ZBBBWXKZYJEBSM-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n',n'-dimethyl-2-phenylacetohydrazide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NN(C)C)C1=CC=CC=C1 ZBBBWXKZYJEBSM-UHFFFAOYSA-N 0.000 claims description 2
- OODOKBUERXZTEM-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(3-ethoxypropyl)-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)NCCCOCC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 OODOKBUERXZTEM-UHFFFAOYSA-N 0.000 claims description 2
- UXKJLKWJOSUXPR-UHFFFAOYSA-N 2-[5-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-3,5-dihydro-2h-1,4-benzothiazepin-4-yl]-n-[(2-ethoxyphenyl)methyl]acetamide Chemical compound CCOC1=CC=CC=C1CNC(=O)CN1C(CC=2C=C(OC)C(OC)=CC=2)C2=CC(OC)=C(OC)C=C2SCC1 UXKJLKWJOSUXPR-UHFFFAOYSA-N 0.000 claims description 2
- GFFQKFRNNGCOSE-UHFFFAOYSA-N 3-[[2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetyl]amino]-n,n-dimethylpropanamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCCC(=O)N(C)C)C1=CC=CC=C1 GFFQKFRNNGCOSE-UHFFFAOYSA-N 0.000 claims description 2
- CVEIPOOXVGYTRS-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-8-hydroxy-7-methoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(O)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(OCO2)C2=C1 CVEIPOOXVGYTRS-UHFFFAOYSA-N 0.000 claims description 2
- HKQKTAMBBMTGDD-GEVKEYJPSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[(1s)-1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1C[C@H]1C2=CC(OC)=C(OC)C=C2CCCN1CC(=O)NC1C2=CC=CC=C2CC1 HKQKTAMBBMTGDD-GEVKEYJPSA-N 0.000 claims description 2
- BTDLTVCMYAYRDQ-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-8-phenylmethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OCC=3C=CC=CC=3)=C(OC)C=C2CCCN1CC(=O)NC1C2=CC=CC=C2CC1 BTDLTVCMYAYRDQ-UHFFFAOYSA-N 0.000 claims description 2
- QUWWIIRDEGPVPH-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7-methoxy-8-propan-2-yloxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC(C)C)=C(OC)C=C2CCCN1CC(=O)NC1C2=CC=CC=C2CC1 QUWWIIRDEGPVPH-UHFFFAOYSA-N 0.000 claims description 2
- YTTRHESSGMDVFM-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-2-[5-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-3,5-dihydro-2h-1,4-benzothiazepin-4-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2SCCN1CC(=O)NC1C2=CC=CC=C2CC1 YTTRHESSGMDVFM-UHFFFAOYSA-N 0.000 claims description 2
- LKLCKJXNZVHPQW-MHZLTWQESA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[(1s)-1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1C[C@H]1C2=CC(OC)=C(OC)C=C2CCCN1CC(=O)NC1CC2=CC=CC=C2C1 LKLCKJXNZVHPQW-MHZLTWQESA-N 0.000 claims description 2
- ZJZWVHWOXORAAE-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[5-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-3,5-dihydro-2h-1,4-benzoxazepin-4-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2OCCN1CC(=O)NC1CC2=CC=CC=C2C1 ZJZWVHWOXORAAE-UHFFFAOYSA-N 0.000 claims description 2
- QGZYCUYEJPDFOZ-UHFFFAOYSA-N n-(2-acetamidoethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCCNC(C)=O)C1=CC=CC=C1 QGZYCUYEJPDFOZ-UHFFFAOYSA-N 0.000 claims description 2
- QKODOALLIMEFAQ-UHFFFAOYSA-N n-(cyanomethyl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCC#N)C1=CC=CC=C1 QKODOALLIMEFAQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 3
- TZMDABMYCCOVGU-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenyl-n-[[4-(thiadiazol-4-yl)phenyl]methyl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=CC=C(C=2N=NSC=2)C=C1 TZMDABMYCCOVGU-UHFFFAOYSA-N 0.000 claims 2
- RYNUFMPIFYVFKM-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(2-ethylsulfanylethyl)-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)NCCSCC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 RYNUFMPIFYVFKM-UHFFFAOYSA-N 0.000 claims 2
- GIGVPKZCKOQZGH-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(2-hydroxyethyl)-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCCO)C1=CC=CC=C1 GIGVPKZCKOQZGH-UHFFFAOYSA-N 0.000 claims 2
- VUUZMSGSDIQZMA-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(3,3-dimethylbutyl)-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C(=O)NCCC(C)(C)C)C1=CC=CC=C1 VUUZMSGSDIQZMA-UHFFFAOYSA-N 0.000 claims 2
- UWESTFVGORTPDP-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-(3-methoxypropyl)-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)NCCCOC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 UWESTFVGORTPDP-UHFFFAOYSA-N 0.000 claims 2
- UFYDEPGYHVIHIO-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-[(1-methylindazol-3-yl)methyl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NCC1=NN(C)C2=CC=CC=C12 UFYDEPGYHVIHIO-UHFFFAOYSA-N 0.000 claims 2
- VKYLQGZIXHKRTC-UHFFFAOYSA-N 2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-n-pentan-3-yl-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)NC(CC)CC)N1CCCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 VKYLQGZIXHKRTC-UHFFFAOYSA-N 0.000 claims 2
- HABNXNYVYBOWRY-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-2-[1-[(3,4-dimethoxyphenyl)methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2-benzazepin-2-yl]-2-phenylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCCN1C(C=1C=CC=CC=1)C(=O)NC1CC2=CC=CC=C2C1 HABNXNYVYBOWRY-UHFFFAOYSA-N 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/14—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
- C07D413/02—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
- 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
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- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Obesity (AREA)
- Diabetes (AREA)
- Anesthesiology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/EP2000/013289 WO2002051232A2 (fr) | 2000-12-27 | 2000-12-27 | Nouvelles benzazepines et derives heterocycliques associes |
Publications (1)
Publication Number | Publication Date |
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ZA200303697B true ZA200303697B (en) | 2004-08-13 |
Family
ID=8164232
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Application Number | Title | Priority Date | Filing Date |
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ZA200303697A ZA200303697B (en) | 2000-12-27 | 2003-05-13 | Novel benzazepines and related heterocyclic derivatives which are useful as orexin receptor antagonists. |
Country Status (18)
Country | Link |
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US (1) | US7192950B2 (fr) |
EP (1) | EP1347967B1 (fr) |
JP (1) | JP4219166B2 (fr) |
KR (1) | KR100849569B1 (fr) |
CN (1) | CN1261430C (fr) |
AT (1) | ATE381560T1 (fr) |
AU (1) | AU2002240855B2 (fr) |
BR (1) | BR0116505A (fr) |
CA (1) | CA2431982C (fr) |
DE (1) | DE60132017T2 (fr) |
ES (1) | ES2296825T3 (fr) |
HU (1) | HUP0301665A3 (fr) |
IL (2) | IL155806A0 (fr) |
MX (1) | MXPA03004779A (fr) |
NO (1) | NO326158B1 (fr) |
NZ (1) | NZ525613A (fr) |
WO (2) | WO2002051232A2 (fr) |
ZA (1) | ZA200303697B (fr) |
Families Citing this family (89)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2446696A1 (fr) * | 2001-06-07 | 2002-12-12 | Neuro3D | Inhibiteurs des phosphodiesterases des nucleotides cycliques, preparation et utilisations de ces inhibiteurs |
US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
WO2004033418A2 (fr) * | 2002-10-11 | 2004-04-22 | Actelion Pharmaceuticals Ltd. | Derives d'acide sulfonylamino-acetique |
US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
JP4637089B2 (ja) * | 2003-03-26 | 2011-02-23 | アクテリオン ファーマシューティカルズ リミテッド | アセトアミド誘導体 |
US7321065B2 (en) * | 2003-04-18 | 2008-01-22 | The Regents Of The University Of California | Thyronamine derivatives and analogs and methods of use thereof |
US7538109B2 (en) | 2003-04-28 | 2009-05-26 | Actelion Pharmaceuticals Ltd | Quinoxalin-3-one derivatives as orexin receptor antagonists |
WO2005005392A1 (fr) * | 2003-07-07 | 2005-01-20 | Ionix Pharmaceuticals Limited | Composes azacycliques convenant comme inhibiteurs des canaux specifiques des neurones sensoriels |
WO2005028438A1 (fr) | 2003-09-22 | 2005-03-31 | Banyu Pharmaceutical Co., Ltd. | Nouveau derive de piperidine |
US8710045B2 (en) | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
SI1751111T1 (sl) * | 2004-03-01 | 2015-04-30 | Actelion Pharmaceuticals Ltd. | Substituirani 1,2,3,4-tetrahidroizokinolinski derivati |
EP2305352A1 (fr) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | Inhibiteurs de la 5-alpha-reductase pour le traitement d'hommes aux troubles métaboliques et anthropométriques |
EP1814590B2 (fr) | 2004-11-01 | 2013-12-11 | Amylin Pharmaceuticals, Inc. | Traitement contre l'obesite ainsi que les maladies associees a l'obesite |
US8394765B2 (en) | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
GB0500300D0 (en) * | 2005-01-07 | 2005-02-16 | Ionix Pharmaceuticals Ltd | Chemical compositions |
US20090286723A1 (en) | 2005-02-11 | 2009-11-19 | Amylin Pharmaceuticals, Inc. | Hybrid Polypeptides with Selectable Properties |
US7501395B2 (en) | 2005-04-25 | 2009-03-10 | Eisai R & D Management Co., Ltd. | Method of screening for antianxiety drugs |
US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
ES2574014T3 (es) | 2005-05-30 | 2016-06-14 | Msd K.K. | Derivado de piperidina novedoso |
EP1916239A4 (fr) | 2005-08-10 | 2009-10-21 | Banyu Pharma Co Ltd | Composé de pyridone |
BRPI0614649A2 (pt) | 2005-08-11 | 2011-04-12 | Amylin Pharmaceuticals Inc | polipeptìdeos hìbridos com propriedades selecionáveis |
EP1921065B1 (fr) | 2005-08-24 | 2010-10-20 | Banyu Pharmaceutical Co., Ltd. | Dérivé phénylpyridone |
WO2007029847A1 (fr) | 2005-09-07 | 2007-03-15 | Banyu Pharmaceutical Co., Ltd. | Dérivé de pyridone substitué aromatique bicylique |
EP1940842B1 (fr) | 2005-09-29 | 2012-05-30 | Merck Sharp & Dohme Corp. | Dérivés acylés de spiropipéridine en tant que modulateurs du récepteur de la mélanocortine-4 |
BRPI0617621A2 (pt) | 2005-10-21 | 2011-08-02 | Novartis Ag | combinação de compostos orgánicos |
AU2006307046A1 (en) | 2005-10-27 | 2007-05-03 | Msd K.K. | Novel benzoxathiin derivative |
MY146564A (en) | 2005-11-10 | 2012-08-30 | Msd Kk | Aza-substituted spiro derivatives |
MX2008011647A (es) * | 2006-03-15 | 2008-09-22 | Actelion Pharmaceuticals Ltd | Derivados de tetrahidroisoquinolina para mejorar la funcion de la memoria. |
MX2008013238A (es) * | 2006-04-12 | 2008-10-21 | Merck & Co Inc | Antagonistas de los canales de calcio de tipo t de piridil amida. |
WO2007122591A2 (fr) | 2006-04-26 | 2007-11-01 | Actelion Pharmaceuticals Ltd | Nouveaux dérivés de pyrazolo-tétrahydropyridine |
WO2008008517A2 (fr) | 2006-07-14 | 2008-01-17 | Merck & Co., Inc. | Diazépans pontés antagonistes du récepteur de l'oréxine |
ES2339822T3 (es) * | 2006-08-28 | 2010-05-25 | Actelion Pharmaceuticals Ltd. | Derivados de 1,4,5,6,7,8-hexahidro-1,2,5-triaza-azuleno como antagonistas del receptor de orexina. |
EP2698157B1 (fr) | 2006-09-22 | 2015-05-20 | Merck Sharp & Dohme Corp. | Procédé de traitement utilisant des inhibiteurs de synthèse d'acide gras |
WO2008038692A1 (fr) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | dÉrivÉ de diarylcÉtimine |
US8263587B2 (en) | 2006-11-02 | 2012-09-11 | Piramal Healthcare Limited | Benzoxazepine compounds, their preparation and use |
PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
EP2125823B1 (fr) | 2006-12-22 | 2012-02-15 | Actelion Pharmaceuticals Ltd. | Dérivés de 5,6,7,8-tétrahydro-imidazo[1,5-a]pyrazine |
JP5497429B2 (ja) | 2007-03-07 | 2014-05-21 | 武田薬品工業株式会社 | ベンゾオキサゼピン誘導体およびその用途 |
AU2008233662B2 (en) | 2007-04-02 | 2012-08-23 | Msd K.K. | Indoledione derivative |
WO2008122513A1 (fr) * | 2007-04-04 | 2008-10-16 | F. Hoffmann-La Roche Ag | Composés hétérocycliques en tant qu'antagonistes des récepteurs d'orexine |
JP2010526825A (ja) | 2007-05-10 | 2010-08-05 | エーエムアール テクノロジー インコーポレイテッド | アリール置換およびヘテロアリール置換テトラヒドロベンゾ−1,4−ジアゼピンならびにノルエピネフリン、ドーパミンおよびセロトニンの再取り込みを遮断するためのその使用 |
EP2150114A4 (fr) | 2007-05-18 | 2012-01-18 | Merck Sharp & Dohme | Antagonistes des récepteurs de l'oréxine à diazépam à pont oxo |
RU2470021C2 (ru) | 2007-05-23 | 2012-12-20 | Мерк Шарп Энд Домэ Корп. | Пиридилпиперидиновые антагонисты рецептора орексинов |
WO2008150364A1 (fr) | 2007-05-23 | 2008-12-11 | Merck & Co., Inc. | Antagonistes du récepteur de la cyclopropylpyrrolidine orexine |
US7879802B2 (en) | 2007-06-04 | 2011-02-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
CA2698912A1 (fr) * | 2007-09-11 | 2009-03-19 | Mondobiotech Laboratories Ag | Utilisation d'un peptide en tant qu'agent therapeutique |
US8637513B2 (en) * | 2007-10-24 | 2014-01-28 | Merck Sharp & Dohme Corp. | Heterocycle phenyl amide T-type calcium channel antagonists |
JP5829399B2 (ja) | 2007-12-28 | 2015-12-09 | アクテリオン ファーマシューティカルズ リミテッドActelion Pharmaceuticals Ltd | 3置換3,4−ジヒドロ−1h−イソキノリン化合物、その製造方法及びその使用 |
CA2714617A1 (fr) | 2008-03-06 | 2009-09-11 | Banyu Pharmaceutical Co., Ltd. | Derive d'alkylaminopyridine |
US20110015198A1 (en) | 2008-03-28 | 2011-01-20 | Banyu Pharmaceutical Co., Inc. | Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism |
EP3239170B1 (fr) | 2008-06-04 | 2019-03-20 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utile dans le traitement de troubles gastro-intestinaux, d'une inflammation, d'un cancer et d'autres troubles |
EP2301936A1 (fr) | 2008-06-19 | 2011-03-30 | Banyu Pharmaceutical Co., Ltd. | Dérivé de spirodiamine-diarylcétoxime |
EP3241839B1 (fr) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonistes de guanylate cyclase utiles pour le traitement de troubles gastro-intestinaux, inflammatoires, cancéreux et autres |
EP2319841A1 (fr) | 2008-07-30 | 2011-05-11 | Msd K.K. | Dérivé de cycloalkylamine à noyaux fusionnés à (5 chaînons)-(5 chaînons) ou (5 chaînons) (6 chaînons) |
CA2741125A1 (fr) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Nouveaux derives de benzimidazole cycliques utiles comme agents anti-diabetiques |
WO2010051206A1 (fr) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Nouveaux agents antidiabétiques utiles avec des dérivés de benzimidazole cycliques |
US20110243940A1 (en) | 2008-12-16 | 2011-10-06 | Schering Corporation | Bicyclic pyranone derivatives and methods of use thereof |
EP2379547A1 (fr) | 2008-12-16 | 2011-10-26 | Schering Corporation | Dérivés de pyridopyrimidine et leurs procédés d'utilisation |
CN102459248A (zh) * | 2009-05-26 | 2012-05-16 | 埃克塞里艾克西斯公司 | 作为PI3K/mTOR抑制剂的苯并氧杂环庚三烯以及它们使用与制造方法 |
EP2504316A1 (fr) | 2009-11-23 | 2012-10-03 | MSD Oss B.V. | Composés hétérocyliques en tant qu'antagonistes des récepteurs d'orexine |
FR2956401B1 (fr) | 2010-02-17 | 2012-02-03 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
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US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
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AU2012311599B2 (en) | 2011-09-19 | 2017-07-06 | Eth Zurich | Ror gamma modulators |
AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
WO2013119639A1 (fr) | 2012-02-07 | 2013-08-15 | Eolas Therapeutics, Inc. | Pipéridines/prolines substituées en tant qu'antagonistes du récepteur de l'orexine |
US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
EP2870144B1 (fr) | 2012-07-03 | 2017-04-19 | Heptares Therapeutics Limited | Antagonistes du récepteur de l'orexine |
AU2013296470B2 (en) | 2012-08-02 | 2016-03-17 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
AU2014219020A1 (en) | 2013-02-22 | 2015-07-23 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
WO2014139388A1 (fr) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Nouveaux dérivés d'indole utiles en tant qu'agents antidiabétiques |
CA2905435A1 (fr) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions utiles pour le traitement de troubles gastro-intestinaux |
US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
EP2781217A1 (fr) | 2013-03-18 | 2014-09-24 | ETH Zurich | Modulateurs de la gamma ROR |
JP6606491B2 (ja) | 2013-06-05 | 2019-11-13 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼcの超高純度アゴニスト、その作成および使用方法 |
WO2015051496A1 (fr) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Composés tricycliques antidiabétiques |
WO2016025669A1 (fr) | 2014-08-13 | 2016-02-18 | Eolas Therapeutics, Inc. | Difluoropyrrolidines en tant que modulateurs des récepteurs de l'orexine |
JP6769963B2 (ja) | 2014-08-29 | 2020-10-14 | ティエエッセ ファルマ ソチエタ レスポンサビリタ リミタータ | α−アミノ−β−カルボキシムコン酸セミアルデヒド脱炭酸酵素の阻害剤 |
GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
GB201601301D0 (en) * | 2016-01-25 | 2016-03-09 | Takeda Pharmaceutical | Novel compounds |
CN109219606B (zh) | 2016-02-12 | 2021-10-01 | 阿斯利康(瑞典)有限公司 | 食欲素受体调节剂的卤素取代的哌啶 |
US20190151304A1 (en) | 2016-05-10 | 2019-05-23 | Inserm (Institut National De La Santé Et De La Rechercjae Médicale | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory |
AU2017342083A1 (en) | 2016-10-14 | 2019-04-11 | Tes Pharma S.R.L. | Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase |
EP3551176A4 (fr) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | Composés hétérocycliques antidiabétiques |
EP3558298A4 (fr) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | Composés de spirochromane antidiabétiques |
GB201718256D0 (en) * | 2017-11-03 | 2017-12-20 | Heptares Therapeutics Ltd | Ox1 antagonists |
KR20210111248A (ko) | 2018-11-20 | 2021-09-10 | 테스 파마 에스.알.엘. | α-아미노-β-카르복시뮤콘산 세미알데하이드 데카르복실라제의 저해제 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3236838A (en) * | 1964-06-09 | 1966-02-22 | Hoffmann La Roche | Certain 1-substituted-benzodiazepin-2-one compounds |
US3480714A (en) * | 1966-02-07 | 1969-11-25 | Ciba Geigy Corp | N-substituted isoquinolines as antiprotozoal agents |
SK4782001A3 (en) | 1998-10-08 | 2001-11-06 | Smithkline Beecham Plc | Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents) |
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2000
- 2000-12-27 WO PCT/EP2000/013289 patent/WO2002051232A2/fr active Application Filing
-
2001
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- 2001-12-19 ES ES01988048T patent/ES2296825T3/es not_active Expired - Lifetime
- 2001-12-19 KR KR1020037008764A patent/KR100849569B1/ko not_active IP Right Cessation
- 2001-12-19 EP EP01988048A patent/EP1347967B1/fr not_active Expired - Lifetime
- 2001-12-19 NZ NZ525613A patent/NZ525613A/en not_active IP Right Cessation
- 2001-12-19 IL IL15580601A patent/IL155806A0/xx active IP Right Grant
- 2001-12-19 CN CNB018208762A patent/CN1261430C/zh not_active Expired - Fee Related
- 2001-12-19 DE DE60132017T patent/DE60132017T2/de not_active Expired - Lifetime
- 2001-12-19 JP JP2002552933A patent/JP4219166B2/ja not_active Expired - Fee Related
- 2001-12-19 CA CA2431982A patent/CA2431982C/fr not_active Expired - Fee Related
- 2001-12-19 WO PCT/EP2001/015074 patent/WO2002051838A1/fr active IP Right Grant
- 2001-12-19 AT AT01988048T patent/ATE381560T1/de active
- 2001-12-19 AU AU2002240855A patent/AU2002240855B2/en not_active Ceased
- 2001-12-19 HU HU0301665A patent/HUP0301665A3/hu unknown
- 2001-12-19 US US10/450,420 patent/US7192950B2/en not_active Expired - Fee Related
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- 2003-05-08 IL IL155806A patent/IL155806A/en not_active IP Right Cessation
- 2003-05-13 ZA ZA200303697A patent/ZA200303697B/en unknown
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Also Published As
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---|---|
HUP0301665A2 (en) | 2008-07-28 |
WO2002051232A2 (fr) | 2002-07-04 |
BR0116505A (pt) | 2004-02-03 |
JP4219166B2 (ja) | 2009-02-04 |
CA2431982C (fr) | 2010-07-20 |
JP2004516324A (ja) | 2004-06-03 |
AU2002240855B2 (en) | 2006-08-17 |
IL155806A0 (en) | 2003-12-23 |
IL155806A (en) | 2008-03-20 |
MXPA03004779A (es) | 2003-09-25 |
EP1347967A1 (fr) | 2003-10-01 |
US7192950B2 (en) | 2007-03-20 |
ATE381560T1 (de) | 2008-01-15 |
CA2431982A1 (fr) | 2002-07-04 |
US20040058912A1 (en) | 2004-03-25 |
CN1261430C (zh) | 2006-06-28 |
CN1481380A (zh) | 2004-03-10 |
NO326158B1 (no) | 2008-10-13 |
DE60132017T2 (de) | 2008-12-04 |
KR100849569B1 (ko) | 2008-07-31 |
WO2002051838A1 (fr) | 2002-07-04 |
NO20032905D0 (no) | 2003-06-24 |
KR20030069199A (ko) | 2003-08-25 |
DE60132017D1 (de) | 2008-01-31 |
ES2296825T3 (es) | 2008-05-01 |
HUP0301665A3 (en) | 2008-12-29 |
NZ525613A (en) | 2005-01-28 |
NO20032905L (no) | 2003-06-24 |
EP1347967B1 (fr) | 2007-12-19 |
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