CA2482655C - Substituted indoles - Google Patents
Substituted indoles Download PDFInfo
- Publication number
- CA2482655C CA2482655C CA2482655A CA2482655A CA2482655C CA 2482655 C CA2482655 C CA 2482655C CA 2482655 A CA2482655 A CA 2482655A CA 2482655 A CA2482655 A CA 2482655A CA 2482655 C CA2482655 C CA 2482655C
- Authority
- CA
- Canada
- Prior art keywords
- indol
- propyl
- carbonitrile
- formula
- compound
- 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.)
- Expired - Fee Related
Links
- 150000002475 indoles Chemical class 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 176
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 239000012453 solvate Substances 0.000 claims abstract description 25
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 18
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 13
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 12
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 11
- 230000000694 effects Effects 0.000 claims abstract description 11
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 10
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 10
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 10
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 10
- 206010015037 epilepsy Diseases 0.000 claims abstract description 8
- 230000007574 infarction Effects 0.000 claims abstract description 8
- 239000003194 amino acid receptor blocking agent Substances 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 104
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 32
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 101100439663 Arabidopsis thaliana CHR7 gene Proteins 0.000 claims description 23
- 125000003003 spiro group Chemical group 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 229910021645 metal ion Inorganic materials 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 210000004556 brain Anatomy 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- BQFVQUWWCSIHEW-UHFFFAOYSA-N 6-[3-[4-(4-cyano-3-methoxyphenyl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C(C#N)C(OC)=CC(N2CCN(CCCC=3C=C4NC=C(C4=CC=3)C#N)CC2)=C1 BQFVQUWWCSIHEW-UHFFFAOYSA-N 0.000 claims description 5
- 208000032841 Bulimia Diseases 0.000 claims description 5
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000020358 Learning disease Diseases 0.000 claims description 5
- 208000026139 Memory disease Diseases 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 201000003723 learning disability Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- DIAOOLPCGOOIHV-UHFFFAOYSA-N 3-[1-[3-(3-cyano-1h-indol-5-yl)propyl]piperidin-4-yl]-1h-indole-5-carboxamide Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCC(CC2)C2=CNC3=CC=C(C=C32)C(=O)N)=C1 DIAOOLPCGOOIHV-UHFFFAOYSA-N 0.000 claims description 4
- GEFZYOPEZYLNCJ-UHFFFAOYSA-N 4-[1-[3-(3-cyano-1h-indol-6-yl)propyl]piperidin-4-yl]oxybenzamide Chemical compound C1=CC(C(=O)N)=CC=C1OC1CCN(CCCC=2C=C3NC=C(C3=CC=2)C#N)CC1 GEFZYOPEZYLNCJ-UHFFFAOYSA-N 0.000 claims description 4
- BFLZMCZQKOZXEG-UHFFFAOYSA-N 5-[3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl]-1h-indole-3-carbonitrile Chemical compound C1CN(CCCC=2C=C3C(C#N)=CNC3=CC=2)CCC11C(=O)NCN1C1=CC=CC=C1 BFLZMCZQKOZXEG-UHFFFAOYSA-N 0.000 claims description 4
- FNYSVQHTACRZCQ-UHFFFAOYSA-N 5-[3-(4-quinolin-8-ylpiperazin-1-yl)propyl]-1h-indole-3-carbonitrile Chemical compound C1=CN=C2C(N3CCN(CC3)CCCC3=CC=C4NC=C(C4=C3)C#N)=CC=CC2=C1 FNYSVQHTACRZCQ-UHFFFAOYSA-N 0.000 claims description 4
- LHBNXAJKGKFNQP-UHFFFAOYSA-N 5-[3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(N3CCN(CC3)CCCC3=CC=C4NC=C(C4=C3)C#N)=NSC2=C1 LHBNXAJKGKFNQP-UHFFFAOYSA-N 0.000 claims description 4
- ZKHNWRRKOTXSPJ-UHFFFAOYSA-N 5-[3-[4-(1h-indol-4-yl)piperazin-1-yl]propyl]-1-methylsulfonylindole-3-carbonitrile Chemical compound C=1C=C2N(S(=O)(=O)C)C=C(C#N)C2=CC=1CCCN(CC1)CCN1C1=CC=CC2=C1C=CN2 ZKHNWRRKOTXSPJ-UHFFFAOYSA-N 0.000 claims description 4
- CJNKOGGPTBTMSU-UHFFFAOYSA-N 5-[3-[4-(1h-indol-4-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2C(C#N)=CNC2=CC=C1CCCN(CC1)CCN1C1=CC=CC2=C1C=CN2 CJNKOGGPTBTMSU-UHFFFAOYSA-N 0.000 claims description 4
- LWDPDVUFDXJIOG-UHFFFAOYSA-N 5-[3-[4-(2,1,3-benzothiadiazol-4-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=CC2=NSN=C2C(N2CCN(CC2)CCCC2=CC=C3NC=C(C3=C2)C#N)=C1 LWDPDVUFDXJIOG-UHFFFAOYSA-N 0.000 claims description 4
- OMOPFUXSBWKXBT-UHFFFAOYSA-N 5-[3-[4-(2-oxochromen-6-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C=2C=C3C=CC(OC3=CC=2)=O)=C1 OMOPFUXSBWKXBT-UHFFFAOYSA-N 0.000 claims description 4
- PJUOUUCPBVTXOS-UHFFFAOYSA-N 5-[3-[4-(4-cyanophenyl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2C(C#N)=CNC2=CC=C1CCCN(CC1)CCN1C1=CC=C(C#N)C=C1 PJUOUUCPBVTXOS-UHFFFAOYSA-N 0.000 claims description 4
- KDNJQJFKQOOBMJ-UHFFFAOYSA-N 5-[3-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C(C#N)C=C2C(C3CCN(CC3)CCCC3=CC=C4NC=C(C4=C3)C#N)=CNC2=C1 KDNJQJFKQOOBMJ-UHFFFAOYSA-N 0.000 claims description 4
- JWJKRLHAJXYPOD-UHFFFAOYSA-N 5-[3-[4-(6-fluoro-1h-indol-3-yl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCC(CC2)C=2C3=CC=C(C=C3NC=2)F)=C1 JWJKRLHAJXYPOD-UHFFFAOYSA-N 0.000 claims description 4
- LARCQYXEUOOVJI-UHFFFAOYSA-N 5-[4-[3-(3-cyano-1h-indol-4-yl)propyl]piperazin-1-yl]-1-benzofuran-2-carboxamide Chemical compound C=1C=C2OC(C(=O)N)=CC2=CC=1N(CC1)CCN1CCCC1=CC=CC2=C1C(C#N)=CN2 LARCQYXEUOOVJI-UHFFFAOYSA-N 0.000 claims description 4
- VUAQTHXRQVAQCD-UHFFFAOYSA-N 6-[3-[4-(2-cyano-3-methoxyphenyl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound COC1=CC=CC(N2CCN(CCCC=3C=C4NC=C(C4=CC=3)C#N)CC2)=C1C#N VUAQTHXRQVAQCD-UHFFFAOYSA-N 0.000 claims description 4
- WCBZWCPBDGJJFQ-UHFFFAOYSA-N 6-[3-[4-(4-cyano-2-methoxyphenyl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound COC1=CC(C#N)=CC=C1N1CCN(CCCC=2C=C3NC=C(C3=CC=2)C#N)CC1 WCBZWCPBDGJJFQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 4
- 210000000278 spinal cord Anatomy 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- IZNRPDFMASPLES-UHFFFAOYSA-N 5-[3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1CCCC1=CC=C2NC=C(C#N)C2=C1 IZNRPDFMASPLES-UHFFFAOYSA-N 0.000 claims description 3
- QPLGCQCJAORPKN-UHFFFAOYSA-N 5-[3-[4-(4-fluoro-1h-indol-3-yl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCC(CC2)C2=CNC=3C=CC=C(C2=3)F)=C1 QPLGCQCJAORPKN-UHFFFAOYSA-N 0.000 claims description 3
- QPLROEKPKXETSR-UHFFFAOYSA-N 5-[4-[3-(3-cyano-1h-indol-5-yl)propyl]piperazin-1-yl]-1-benzofuran-2-carboxamide Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C=2C=C3C=C(OC3=CC=2)C(=O)N)=C1 QPLROEKPKXETSR-UHFFFAOYSA-N 0.000 claims description 3
- SOZNTAIYBKHATH-UHFFFAOYSA-N 5-[4-[3-(3-cyano-1h-indol-6-yl)propyl]piperazin-1-yl]-1-benzofuran-2-carboxamide Chemical compound C1=C2C(C#N)=CNC2=CC(CCCN2CCN(CC2)C=2C=C3C=C(OC3=CC=2)C(=O)N)=C1 SOZNTAIYBKHATH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
- XEXLBCQWMFOPLY-UHFFFAOYSA-N 2-[4-[3-(3-cyano-1h-indol-5-yl)propyl]piperazin-1-yl]-1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC(N2CCN(CCCC=3C=C4C(C#N)=CNC4=CC=3)CC2)=N1 XEXLBCQWMFOPLY-UHFFFAOYSA-N 0.000 claims description 2
- PJMFZXWLBNTPPK-UHFFFAOYSA-N 4-[3-[4-(pyrazol-1-ylmethyl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C=12C(C#N)=CNC2=CC=CC=1CCCN(CC1)CCC1CN1C=CC=N1 PJMFZXWLBNTPPK-UHFFFAOYSA-N 0.000 claims description 2
- QXWBWDNCQPWTRZ-UHFFFAOYSA-N 5-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2C(C#N)=CNC2=CC=C1CCCN(CC1)CCN1C1=NC=CC=N1 QXWBWDNCQPWTRZ-UHFFFAOYSA-N 0.000 claims description 2
- PUYTZMAGOKFVTQ-UHFFFAOYSA-N 5-[3-(pyridin-3-ylmethylamino)propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2C(C#N)=CNC2=CC=C1CCCNCC1=CC=CN=C1 PUYTZMAGOKFVTQ-UHFFFAOYSA-N 0.000 claims description 2
- RQOYNNPRLDBPRW-UHFFFAOYSA-N 5-[3-[3-(2-oxopyrrolidin-1-yl)propylamino]propyl]-1h-indole-3-carbonitrile Chemical compound O=C1CCCN1CCCNCCCC1=CC=C(NC=C2C#N)C2=C1 RQOYNNPRLDBPRW-UHFFFAOYSA-N 0.000 claims description 2
- LRQYBPXGUKKCLK-UHFFFAOYSA-N 5-[3-[4-(1-methylimidazo[4,5-c]pyridin-4-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C2=C3N=CN(C3=CC=N2)C)=C1 LRQYBPXGUKKCLK-UHFFFAOYSA-N 0.000 claims description 2
- LGAAYAVRUVTFKS-UHFFFAOYSA-N 5-[3-[4-(1h-indol-3-yl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C3CCN(CC3)CCCC3=CC=C4NC=C(C4=C3)C#N)=CNC2=C1 LGAAYAVRUVTFKS-UHFFFAOYSA-N 0.000 claims description 2
- NRDSZFOFPWXWBE-UHFFFAOYSA-N 5-[3-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound O1CCOC2=CC(N3CCN(CC3)CCCC3=CC=C4NC=C(C4=C3)C#N)=CC=C21 NRDSZFOFPWXWBE-UHFFFAOYSA-N 0.000 claims description 2
- IBBLTAZDDRHFHT-UHFFFAOYSA-N 5-[3-[4-(3-amino-2-oxochromen-6-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C=2C=C3C=C(C(OC3=CC=2)=O)N)=C1 IBBLTAZDDRHFHT-UHFFFAOYSA-N 0.000 claims description 2
- UQALVGIRSOKDSG-UHFFFAOYSA-N 5-[3-[4-(3-methoxyphenyl)-3-methylpiperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound COC1=CC=CC(N2C(CN(CCCC=3C=C4C(C#N)=CNC4=CC=3)CC2)C)=C1 UQALVGIRSOKDSG-UHFFFAOYSA-N 0.000 claims description 2
- KOFWLCKXTCSTHI-UHFFFAOYSA-N 5-[3-[4-(4-pyridin-3-yl-1,3-thiazol-2-yl)piperazin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2C(C#N)=CNC2=CC=C1CCCN(CC1)CCN1C(SC=1)=NC=1C1=CC=CN=C1 KOFWLCKXTCSTHI-UHFFFAOYSA-N 0.000 claims description 2
- FICXHYVHQPSCLK-UHFFFAOYSA-N 5-[3-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]propyl]-1h-indole-3-carbonitrile Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCC(CC2)C2=CNC3=CC=C(C=C32)F)=C1 FICXHYVHQPSCLK-UHFFFAOYSA-N 0.000 claims description 2
- 208000028698 Cognitive impairment Diseases 0.000 claims description 2
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- 206010057852 Nicotine dependence Diseases 0.000 claims description 2
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- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- JMUKSNFJRVESEX-UHFFFAOYSA-N ethyl 2-[4-[3-(3-cyano-1h-indol-5-yl)propyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N2CCN(CCCC=3C=C4C(C#N)=CNC4=CC=3)CC2)=N1 JMUKSNFJRVESEX-UHFFFAOYSA-N 0.000 claims description 2
- 210000004558 lewy body Anatomy 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims description 2
- IFSGUQUAEWNKEB-UHFFFAOYSA-N methyl n-[6-[4-[3-(3-cyano-1h-indol-5-yl)propyl]piperazin-1-yl]-2-oxochromen-3-yl]carbamate Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C=2C=C3C=C(C(OC3=CC=2)=O)NC(=O)OC)=C1 IFSGUQUAEWNKEB-UHFFFAOYSA-N 0.000 claims description 2
- XASTVLSRTKFVEJ-UHFFFAOYSA-N n-[4-[[1-[3-(3-cyano-1h-indol-5-yl)propyl]piperidin-4-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CC1CCN(CCCC=2C=C3C(C#N)=CNC3=CC=2)CC1 XASTVLSRTKFVEJ-UHFFFAOYSA-N 0.000 claims description 2
- PRNVNPAKZNKDJU-UHFFFAOYSA-N n-[6-[4-[3-(3-cyano-1h-indol-5-yl)propyl]piperazin-1-yl]-2-oxochromen-3-yl]acetamide Chemical compound C1=C2NC=C(C#N)C2=CC(CCCN2CCN(CC2)C=2C=C3C=C(C(OC3=CC=2)=O)NC(=O)C)=C1 PRNVNPAKZNKDJU-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000028252 learning or memory Effects 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 10
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- -1 bicyclic heterocyclic radical Chemical class 0.000 description 89
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- 239000004480 active ingredient Substances 0.000 description 22
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
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- 239000000243 solution Substances 0.000 description 20
- 101100439664 Arabidopsis thaliana CHR8 gene Proteins 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000009739 binding Methods 0.000 description 16
- 230000027455 binding Effects 0.000 description 16
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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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- 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
- C07D401/14—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 three or more hetero rings
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- 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
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- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/14—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 three or more hetero rings
-
- 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
- C07D471/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
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- Psychiatry (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Diabetes (AREA)
- Psychology (AREA)
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- Gynecology & Obstetrics (AREA)
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- Child & Adolescent Psychology (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10217006A DE10217006A1 (de) | 2002-04-16 | 2002-04-16 | Substituierte Indole |
| DE10217006.1 | 2002-04-16 | ||
| PCT/EP2003/003806 WO2003087086A2 (de) | 2002-04-16 | 2003-04-11 | Substituierte indole und deren verwendung als 5ht-wiederaufnahme inhibitoren und als 5ht liganden |
Publications (2)
| Publication Number | Publication Date |
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| CA2482655A1 CA2482655A1 (en) | 2003-10-23 |
| CA2482655C true CA2482655C (en) | 2011-08-16 |
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| CA2482655A Expired - Fee Related CA2482655C (en) | 2002-04-16 | 2003-04-11 | Substituted indoles |
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| Country | Link |
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| JP (1) | JP2005523310A (enExample) |
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| DK (1) | DK1497279T3 (enExample) |
| ES (1) | ES2362871T3 (enExample) |
| WO (1) | WO2003087086A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20050119251A1 (en) * | 2001-12-21 | 2005-06-02 | Jian-Min Fu | Nicotinamide derivatives and their use as therapeutic agents |
| DE10217006A1 (de) * | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| DE10259244A1 (de) * | 2002-12-17 | 2004-07-01 | Merck Patent Gmbh | N-(Indolethyl-)cycloamin-Verbindungen |
| ES2280824T3 (es) * | 2002-12-20 | 2007-09-16 | Merck Patent Gmbh | Benzodioxepinas substituidas. |
| AU2004303461B2 (en) * | 2003-12-23 | 2011-04-28 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-benzyl amine derivatives as SSRI |
| AR052308A1 (es) * | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto |
| EP2400300A1 (en) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Method of screening preventives/remedies for stress urinary incontinence |
| BRPI0515477A (pt) * | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos bicìclicos e o uso dos mesmos como inibidores de estaroil-coa-desaturase (scd) |
| AR051026A1 (es) | 2004-09-20 | 2006-12-13 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| WO2006101521A2 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| US7951805B2 (en) | 2004-09-20 | 2011-05-31 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
| AU2005286647A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| US8071603B2 (en) | 2004-09-20 | 2011-12-06 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| AU2005286846A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
| EP2316458A1 (en) | 2004-09-20 | 2011-05-04 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-coa-desaturase |
| TW200630337A (en) * | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
| DE602005022113D1 (de) * | 2005-01-07 | 2010-08-12 | Hoffmann La Roche | Phenyl)methanon-derivate als glycin-transporter 1 (glyt-1) hemmer zur behandlung von neurologischen und neuropsychiatrischen erkrankungen |
| DE102005019670A1 (de) * | 2005-04-26 | 2006-11-02 | Merck Patent Gmbh | Verfahren zur Herstellung von (5-(4-[4-(5-Cyano-3-indolyl)-butyl)-1-piperazinyl)-benzofuran-2-carboxamid |
| JP2009513563A (ja) * | 2005-06-03 | 2009-04-02 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトのステアロイル−CoAデサチュラーゼ阻害剤としてのアミノチアゾール誘導体 |
| TW200800959A (en) * | 2005-06-10 | 2008-01-01 | Wyeth Corp | Piperazine-piperidine antagonists and agonists of the 5-HT1a receptor |
| MX2007015772A (es) | 2005-06-17 | 2008-02-22 | Wyeth Corp | Compuestos utiles como inhibidores de serotonina y agonistas y antagonistas de 5-ht-1a. |
| AR054393A1 (es) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos. |
| US7629473B2 (en) * | 2005-06-17 | 2009-12-08 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-aryl amine derivatives |
| WO2007007910A1 (ja) * | 2005-07-13 | 2007-01-18 | Banyu Pharmaceutical Co., Ltd. | ヘテロ環置換ベンズイミダゾール誘導体 |
| RU2008127501A (ru) * | 2006-01-13 | 2010-02-20 | Вайет (Us) | Сульфонилзамещенные 1н-индолы в качастве лигандов 5-гидрокситриптаминовых рецепторов |
| US8247442B2 (en) * | 2006-03-29 | 2012-08-21 | Purdue Pharma L.P. | Benzenesulfonamide compounds and their use |
| US8791264B2 (en) * | 2006-04-13 | 2014-07-29 | Purdue Pharma L.P. | Benzenesulfonamide compounds and their use as blockers of calcium channels |
| WO2007118854A1 (en) * | 2006-04-13 | 2007-10-25 | Euro-Celtique S.A. | Benzenesulfonamide compounds and the use thereof |
| 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 |
| WO2008015516A1 (en) * | 2006-07-28 | 2008-02-07 | Pfizer Products Inc. | Fused tricyclic heterocycles for the treatment of schizophrenia |
| US8399486B2 (en) | 2007-04-09 | 2013-03-19 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use thereof |
| JP2010527915A (ja) * | 2007-04-26 | 2010-08-19 | アバロン ファーマシューティカルズ,インコーポレイテッド | 多重環化合物及びその用途 |
| EP2178842A2 (en) | 2007-08-22 | 2010-04-28 | Abbott GmbH & Co. KG | 4-benzylaminoquinolines, pharmaceutical compositions containing them and their use |
| WO2009040659A2 (en) * | 2007-09-28 | 2009-04-02 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| 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 |
| AU2009212259A1 (en) | 2008-02-07 | 2009-08-13 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
| EP2527328A1 (en) * | 2008-04-01 | 2012-11-28 | Abbott GmbH & Co. KG | Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy |
| GB0813142D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| GB0813144D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| CN102498095A (zh) | 2009-02-05 | 2012-06-13 | 国立大学法人京都大学 | 二氢吲哚衍生物 |
| TW201038569A (en) | 2009-02-16 | 2010-11-01 | Abbott Gmbh & Co Kg | Heterocyclic compounds, pharmaceutical compositions containing them, and their use in therapy |
| AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
| EP2413696A4 (en) * | 2009-04-03 | 2012-10-24 | Sinai School Medicine | COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
| US8912220B2 (en) * | 2009-08-10 | 2014-12-16 | Galenea Pharmaceuticals | Compounds and methods of use thereof |
| TWI535440B (zh) * | 2009-10-26 | 2016-06-01 | Lg生命科學有限公司 | 包括吲哚化合物之醫藥組成物 |
| JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
| WO2011106039A1 (en) * | 2010-02-24 | 2011-09-01 | Research Triangle Institute | Arylpiperazone opioid receptor antagonists |
| WO2012014127A1 (en) | 2010-07-30 | 2012-02-02 | Ranbaxy Laboratories Limited | 5-lipoxygenase inhibitors |
| US9045459B2 (en) | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8877794B2 (en) | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9309200B2 (en) | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| PL395470A1 (pl) | 2011-06-29 | 2013-01-07 | Adamed Spólka Z Ograniczona Odpowiedzialnoscia | Sulfonamidowe pochodne amin alicyklicznych do leczenia chorób osrodkowego ukladu nerwowego |
| CN103889968A (zh) | 2011-08-05 | 2014-06-25 | 艾伯维德国有限责任两合公司 | 氨基苯并二氢吡喃、氨基苯并二氢噻喃及氨基-1,2,3,4-四氢喹啉衍生物,包含这些化合物的药用组合物,及其在治疗中的用途 |
| MX2014006004A (es) | 2011-11-18 | 2015-04-16 | Abbvie Deutschland | Derivados de aminobenzociclohepteno, aminotetralina, aminoindano y fenalcilamina n-sustituidas, composiciones farmaceuticas que los contienen, y su uso en terapia. |
| US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9650334B2 (en) | 2013-03-15 | 2017-05-16 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9656955B2 (en) | 2013-03-15 | 2017-05-23 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| JO3425B1 (ar) | 2013-07-15 | 2019-10-20 | Novartis Ag | مشتقات البابيريدينيل-اندول واستخدامها كعامل متمم لمثبطات b |
| AU2014336154A1 (en) | 2013-10-17 | 2016-04-28 | AbbVie Deutschland GmbH & Co. KG | Aminotetraline and aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| JP2016537323A (ja) | 2013-10-17 | 2016-12-01 | アッヴィ・ドイチュラント・ゲー・エム・ベー・ハー・ウント・コー・カー・ゲー | アミノクロマン誘導体、アミノチオクロマン誘導体およびアミノ−1,2,3,4−テトラヒドロキノリン誘導体、これらを含有する医薬組成物、および治療におけるこれらの使用 |
| US9550754B2 (en) | 2014-09-11 | 2017-01-24 | AbbVie Deutschland GmbH & Co. KG | 4,5-dihydropyrazole derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US10633336B2 (en) | 2014-12-19 | 2020-04-28 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
| US10752588B2 (en) | 2014-12-19 | 2020-08-25 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
| EP3597186B1 (en) | 2015-01-05 | 2021-12-08 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Myc g-quadruplex stabilizing small molecules and their use |
| CA3077383A1 (en) | 2017-09-29 | 2019-04-04 | Sunshine Lake Pharma Co., Ltd. | Substituted pyrimidine piperazine compound and use thereof |
| US20210052600A1 (en) | 2017-12-27 | 2021-02-25 | Takeda Pharmaceutical Company Limited | Therapeutic agents for stress urinary incontinence and incotinence of feces |
| CN112851641B (zh) * | 2019-11-28 | 2023-08-15 | 广东东阳光药业股份有限公司 | 嘧啶苯甲酰胺化合物的盐酸盐及其用途 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB132130A (enExample) | 1917-11-10 | |||
| FR1344579A (fr) | 1961-11-23 | 1963-11-29 | Sandoz Sa | Nouveaux dérivés de l'indole et leur préparation |
| CH421107A (de) | 1963-06-04 | 1966-09-30 | Sandoz Ag | Verfahren zur Herstellung neuer heterocyclischer Verbindungen |
| JPS63301862A (ja) * | 1987-01-23 | 1988-12-08 | Yoshitomi Pharmaceut Ind Ltd | 5−ヒドロキシインドール−3−カルボン酸アミド化合物 |
| EP0299076A4 (en) * | 1987-01-23 | 1991-01-09 | Yoshitomi Pharmaceutical Industries, Ltd. | 5-hydroxyindole-3-carboxamide compound and medicinal use thereof |
| DE4101686A1 (de) | 1991-01-22 | 1992-07-23 | Merck Patent Gmbh | Indolderivate |
| DE4127849A1 (de) * | 1991-08-22 | 1993-02-25 | Merck Patent Gmbh | Benzodioxanderivate |
| DE4333254A1 (de) * | 1993-09-30 | 1995-04-06 | Merck Patent Gmbh | Piperidine und Piperazine |
| FR2712591B1 (fr) * | 1993-11-19 | 1996-02-09 | Pf Medicament | Nouvelles arylpipérazines dérivées d'indole, leur préparation et leur utilisation thérapeutique. |
| DE4414113A1 (de) * | 1994-04-22 | 1995-10-26 | Merck Patent Gmbh | 3-Indolylpiperidine |
| CA2194984C (en) | 1994-07-26 | 2002-07-02 | John Eugene Macor | 4-indole derivatives as serotonin agonists and antagonists |
| DE59504622D1 (de) * | 1994-10-31 | 1999-02-04 | Merck Patent Gmbh | Benzylpiperidinderivate mit hoher Affinität zu Bindungsstellen von Aminosäure-Rezeptoren |
| DE19500689A1 (de) * | 1995-01-12 | 1996-07-18 | Merck Patent Gmbh | Indolpiperidin-Derivate |
| US5962473A (en) | 1996-08-16 | 1999-10-05 | Eli Lilly And Company | Methods of treating or ameliorating the symptoms of common cold or allergic rhinitis with serotonin 5-HT1F |
| DE19730989A1 (de) * | 1997-07-18 | 1999-01-21 | Merck Patent Gmbh | Piperazin-Derivate |
| DE69919436T2 (de) * | 1998-04-16 | 2005-09-15 | Pfizer Products Inc., Groton | N-Acyl und N-Aroyl Aralkylamide |
| US6399619B1 (en) * | 1999-04-06 | 2002-06-04 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| TW518218B (en) * | 1999-05-27 | 2003-01-21 | Merck Patent Gmbh | Pharmaceutical compositions comprising 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)piperazine or its physiologically acceptable salts for use in the treatment of sub-type anxiety disorders |
| DE19934433A1 (de) * | 1999-07-22 | 2001-01-25 | Merck Patent Gmbh | N-(Indolcarbonyl-)piperazinderivate |
| DE19934432A1 (de) * | 1999-07-22 | 2001-02-01 | Merck Patent Gmbh | Indolderivate |
| FR2797874B1 (fr) * | 1999-08-27 | 2002-03-29 | Adir | Nouveaux derives de la pyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| DE10041574A1 (de) * | 2000-08-24 | 2002-03-07 | Merck Patent Gmbh | Chromenonderivate |
| GB0203778D0 (en) * | 2002-02-18 | 2002-04-03 | Glaxo Group Ltd | Compounds |
| DE10217006A1 (de) * | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| AU2003268464A1 (en) * | 2002-09-03 | 2004-03-29 | Scios Inc. | INDOLE-TYPE DERIVATIVES AS INHIBITORS OF p38 KINASE |
| US6844362B2 (en) | 2002-10-11 | 2005-01-18 | Pfizer Inc | Indole derivatives useful for the treatment of diseases |
| EP1440966A1 (en) | 2003-01-10 | 2004-07-28 | Pfizer Limited | Indole derivatives useful for the treatment of diseases |
| EP1460064A1 (en) | 2003-03-14 | 2004-09-22 | Pfizer Limited | Indole-2-carboxamide derivatives useful as beta-2 agonists |
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2002
- 2002-04-16 DE DE10217006A patent/DE10217006A1/de not_active Withdrawn
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2003
- 2003-04-11 JP JP2003584042A patent/JP2005523310A/ja active Pending
- 2003-04-11 DK DK03720455.9T patent/DK1497279T3/da active
- 2003-04-11 DE DE50313528T patent/DE50313528D1/de not_active Expired - Lifetime
- 2003-04-11 AT AT03720455T patent/ATE501133T1/de active
- 2003-04-11 US US10/511,155 patent/US7572796B2/en not_active Expired - Fee Related
- 2003-04-11 WO PCT/EP2003/003806 patent/WO2003087086A2/de not_active Ceased
- 2003-04-11 EP EP03720455A patent/EP1497279B1/de not_active Expired - Lifetime
- 2003-04-11 CA CA2482655A patent/CA2482655C/en not_active Expired - Fee Related
- 2003-04-11 ES ES03720455T patent/ES2362871T3/es not_active Expired - Lifetime
- 2003-04-11 AU AU2003224064A patent/AU2003224064A1/en not_active Abandoned
-
2008
- 2008-10-03 US US12/245,416 patent/US8058277B2/en not_active Expired - Fee Related
-
2009
- 2009-07-29 US US12/511,320 patent/US20090291963A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20050153980A1 (en) | 2005-07-14 |
| US20090054459A1 (en) | 2009-02-26 |
| EP1497279A2 (de) | 2005-01-19 |
| AU2003224064A8 (en) | 2003-10-27 |
| CA2482655A1 (en) | 2003-10-23 |
| JP2005523310A (ja) | 2005-08-04 |
| US8058277B2 (en) | 2011-11-15 |
| ATE501133T1 (de) | 2011-03-15 |
| DK1497279T3 (da) | 2011-06-14 |
| US7572796B2 (en) | 2009-08-11 |
| US20090291963A1 (en) | 2009-11-26 |
| ES2362871T3 (es) | 2011-07-14 |
| WO2003087086A2 (de) | 2003-10-23 |
| AU2003224064A1 (en) | 2003-10-27 |
| DE10217006A1 (de) | 2003-11-06 |
| DE50313528D1 (de) | 2011-04-21 |
| WO2003087086A3 (de) | 2004-07-22 |
| EP1497279B1 (de) | 2011-03-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130411 |