SK281423B6 - Kondenzované indolové deriváty, spôsob ich výroby, farmaceutické prostriedky s ich obsahom a ich použitie - Google Patents
Kondenzované indolové deriváty, spôsob ich výroby, farmaceutické prostriedky s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK281423B6 SK281423B6 SK1078-94A SK107894A SK281423B6 SK 281423 B6 SK281423 B6 SK 281423B6 SK 107894 A SK107894 A SK 107894A SK 281423 B6 SK281423 B6 SK 281423B6
- Authority
- SK
- Slovakia
- Prior art keywords
- indole
- methyl
- piperidyl
- butyl
- carboxylate
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title claims abstract description 22
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims description 196
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 238000000034 method Methods 0.000 title description 58
- 230000008569 process Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 230000003042 antagnostic effect Effects 0.000 claims abstract description 12
- 210000000748 cardiovascular system Anatomy 0.000 claims abstract 2
- -1 polymethylene chain Polymers 0.000 claims description 76
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 claims description 5
- 239000003523 serotonin 4 antagonist Substances 0.000 claims description 5
- FDFXXWIRTGBXAR-UHFFFAOYSA-N N-[(1-butylpiperidin-4-yl)methyl]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-4-carboxamide Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCC2 FDFXXWIRTGBXAR-UHFFFAOYSA-N 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- BTYZSXHYCWYSFY-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]-1,2-dihydro-[1,3]thiazolo[3,2-a]indole-4-carboxamide Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCS2 BTYZSXHYCWYSFY-UHFFFAOYSA-N 0.000 claims description 4
- FXCLGAGFIKPOQS-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]-1h-indole-3-carboxamide Chemical compound C1CN(CCCC)CCC1CNC(=O)C1=CNC2=CC=CC=C12 FXCLGAGFIKPOQS-UHFFFAOYSA-N 0.000 claims description 4
- KPZIATSDDGZUBL-UHFFFAOYSA-N C(C1=CC=CC=C1)N1CCC(CC1)C1(OC=CCN1)C Chemical compound C(C1=CC=CC=C1)N1CCC(CC1)C1(OC=CCN1)C KPZIATSDDGZUBL-UHFFFAOYSA-N 0.000 claims description 3
- CZMSZFKGCJGPFG-UHFFFAOYSA-N C(CCC)N1CCC(CC1)C1(OC=CCN1)C Chemical compound C(CCC)N1CCC(CC1)C1(OC=CCN1)C CZMSZFKGCJGPFG-UHFFFAOYSA-N 0.000 claims description 3
- ICFQDFNPEJWVIK-UHFFFAOYSA-N C(CCC)N1CCC(CC1)C1(SC=CCN1)C Chemical compound C(CCC)N1CCC(CC1)C1(SC=CCN1)C ICFQDFNPEJWVIK-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- SCEBJXOEEWIRLI-UHFFFAOYSA-N 2-methyl-3,4-dihydro-2H-1,3-oxazine Chemical compound CC1OC=CCN1 SCEBJXOEEWIRLI-UHFFFAOYSA-N 0.000 claims description 2
- KEDFXANIESZBDM-UHFFFAOYSA-N C(C)N1CCC(CC1)CN1COC=CC1 Chemical compound C(C)N1CCC(CC1)CN1COC=CC1 KEDFXANIESZBDM-UHFFFAOYSA-N 0.000 claims description 2
- WEJGRTKZZGMPCV-UHFFFAOYSA-N C(CCC)N1CCC(CC1)C1(S(C=CCN1)=O)C Chemical compound C(CCC)N1CCC(CC1)C1(S(C=CCN1)=O)C WEJGRTKZZGMPCV-UHFFFAOYSA-N 0.000 claims description 2
- QKWYWRYIAYWJFN-UHFFFAOYSA-N C(CCCCC)N1CCC(CC1)CN1COC=CC1 Chemical compound C(CCCCC)N1CCC(CC1)CN1COC=CC1 QKWYWRYIAYWJFN-UHFFFAOYSA-N 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- QJFNLLQVMIGYEG-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]-[1,3]thiazolo[3,2-a]indole-4-carboxamide Chemical compound C1CN(CCCC)CCC1CNC(=O)C1=C2SC=CN2C2=CC=CC=C21 QJFNLLQVMIGYEG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 6
- UDSZGVPTVATORB-UHFFFAOYSA-N 2,3-dimethyl-2h-1,3-thiazole Chemical compound CC1SC=CN1C UDSZGVPTVATORB-UHFFFAOYSA-N 0.000 claims 1
- DDSZZGMTDFBTAT-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1,3-oxazole Chemical compound CC1NC=CO1 DDSZZGMTDFBTAT-UHFFFAOYSA-N 0.000 claims 1
- YWHKXEYWNMJLKS-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1,3-thiazole Chemical compound CC1NC=CS1 YWHKXEYWNMJLKS-UHFFFAOYSA-N 0.000 claims 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims 1
- WACSBOVYRCUHIC-UHFFFAOYSA-N CC1=C2C(=C3N(C2=CC=C1)CCC=C3)C(=O)OC3CCN(CC3)CCCC Chemical compound CC1=C2C(=C3N(C2=CC=C1)CCC=C3)C(=O)OC3CCN(CC3)CCCC WACSBOVYRCUHIC-UHFFFAOYSA-N 0.000 claims 1
- VIKWXRMCVRWJES-UHFFFAOYSA-N CC1CCN2C1=C(C=1C=CC=CC21)C(=O)OC2CCN(CC2)CCCC Chemical compound CC1CCN2C1=C(C=1C=CC=CC21)C(=O)OC2CCN(CC2)CCCC VIKWXRMCVRWJES-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 210000002249 digestive system Anatomy 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 claims 1
- IPLFQMHVWVHWNH-UHFFFAOYSA-N methyl [1,3]thiazolo[3,2-a]indole-4-carboxylate Chemical compound COC(=O)C1=C2N(C=CS2)C3=CC=CC=C31 IPLFQMHVWVHWNH-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 210000002784 stomach Anatomy 0.000 abstract description 4
- 108091005482 5-HT4 receptors Proteins 0.000 abstract description 2
- 208000015114 central nervous system disease Diseases 0.000 abstract description 2
- 230000001079 digestive effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 146
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 105
- 239000000243 solution Substances 0.000 description 105
- 239000007787 solid Substances 0.000 description 100
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- 238000005160 1H NMR spectroscopy Methods 0.000 description 85
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 50
- 239000000203 mixture Substances 0.000 description 47
- 239000003480 eluent Substances 0.000 description 46
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 39
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- 235000019198 oils Nutrition 0.000 description 37
- 229910052938 sodium sulfate Inorganic materials 0.000 description 37
- 235000011152 sodium sulphate Nutrition 0.000 description 37
- 238000002844 melting Methods 0.000 description 36
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- 238000003756 stirring Methods 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 238000001819 mass spectrum Methods 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 150000003891 oxalate salts Chemical class 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
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- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 13
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- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 11
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 11
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- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 10
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 9
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- 238000010171 animal model Methods 0.000 description 4
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- 150000001721 carbon Chemical group 0.000 description 4
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- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 4
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- KNUKUWNSGVICSX-UHFFFAOYSA-N (1-benzylpiperidin-4-yl)methanamine Chemical compound C1CC(CN)CCN1CC1=CC=CC=C1 KNUKUWNSGVICSX-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/452—Piperidinium derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929205428A GB9205428D0 (en) | 1992-03-12 | 1992-03-12 | Pharmaceuticals |
| GB929218846A GB9218846D0 (en) | 1992-09-05 | 1992-09-05 | Pharmaceuticals |
| GB929227045A GB9227045D0 (en) | 1992-12-29 | 1992-12-29 | Pharmaceuticals |
| PCT/GB1993/000506 WO1993018036A1 (en) | 1992-03-12 | 1993-03-10 | Condensed indole derivatives as 5ht4-receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK107894A3 SK107894A3 (en) | 1995-04-12 |
| SK281423B6 true SK281423B6 (sk) | 2001-03-12 |
Family
ID=27266092
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1078-94A SK281423B6 (sk) | 1992-03-12 | 1993-03-10 | Kondenzované indolové deriváty, spôsob ich výroby, farmaceutické prostriedky s ich obsahom a ich použitie |
Country Status (29)
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| JP (1) | JP2831467B2 (cs) |
| KR (1) | KR100282730B1 (cs) |
| CN (2) | CN1043893C (cs) |
| AP (1) | AP401A (cs) |
| AT (2) | ATE266033T1 (cs) |
| AU (1) | AU671102B2 (cs) |
| CA (1) | CA2131797C (cs) |
| CY (1) | CY2510B1 (cs) |
| CZ (1) | CZ286194B6 (cs) |
| DE (2) | DE69333504T2 (cs) |
| DK (2) | DK0884319T3 (cs) |
| ES (2) | ES2132223T3 (cs) |
| FI (1) | FI107158B (cs) |
| GR (1) | GR3030668T3 (cs) |
| HU (1) | HU219121B (cs) |
| IL (1) | IL105003A (cs) |
| MA (1) | MA22819A1 (cs) |
| MX (1) | MX9301348A (cs) |
| MY (1) | MY110110A (cs) |
| NO (1) | NO303638B1 (cs) |
| NZ (1) | NZ249565A (cs) |
| PT (1) | PT884319E (cs) |
| RU (1) | RU2104279C1 (cs) |
| SG (1) | SG50693A1 (cs) |
| SI (1) | SI9300114B (cs) |
| SK (1) | SK281423B6 (cs) |
| UA (1) | UA41311C2 (cs) |
| WO (1) | WO1993018036A1 (cs) |
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| US5998409A (en) * | 1992-03-12 | 1999-12-07 | Smithkline Beecham Plc | Condensed indole derivatives as 5HT4 -receptor antagonists |
| US5852014A (en) * | 1992-03-12 | 1998-12-22 | Smithkline Beecham P.L.C. | Condensed indole derivatives as 5HT4 -receptor antagonists |
| GB9316195D0 (en) * | 1993-08-05 | 1993-09-22 | Smithkline Beecham Plc | Pharmaceuticals |
| MX9305947A (es) * | 1992-09-29 | 1994-06-30 | Smithkline Beecham Plc | Compuestos antagonistas del receptor 5-ht4, procedimiento para su preparacion y composiciones farmaceuticas que las contienen. |
| EP0664794A1 (en) * | 1992-10-16 | 1995-08-02 | Smithkline Beecham Plc | N-alkylpiperidinyl-4-methyl carboxylic esters/amides of condensed ring systems as 5-ht4 receptor antagonists |
| AU680453B2 (en) * | 1992-11-05 | 1997-07-31 | Smithkline Beecham Plc | Piperidine derivatives as 5-HT4 receptor antagonists |
| FR2699921B1 (fr) * | 1992-12-30 | 1995-02-10 | Synthelabo | Dérivés d'acide 2-(thien-2-yl)imidazo[2,1-b]benzothiazole-3-acétique, leur préparation et leur application en thérapeutique. |
| GB9303340D0 (en) * | 1993-02-19 | 1993-04-07 | Smithkline Beecham Plc | Pharmaceuticals |
| GB9310582D0 (en) * | 1993-05-22 | 1993-07-07 | Smithkline Beecham Plc | Pharmaceuticals |
| GB9312348D0 (en) * | 1993-06-16 | 1993-07-28 | Smithkline Beecham Plc | Pharmaceuticals |
| KR100219922B1 (ko) * | 1996-05-16 | 1999-09-01 | 이서봉 | 신규한 항바이러스성 6-아릴옥시 및 6-아릴카르보닐 2,4-피리미딘디온 유도체 및 그의 제조 방법 |
| WO1998000422A1 (en) * | 1996-07-02 | 1998-01-08 | Sang Sup Jew | Oxirane carboxylic acid derivative and its manufacturing method |
| US6100397A (en) * | 1996-08-16 | 2000-08-08 | Smithkline Beecham Plc | Process for the preparation of N-[(1-n butyl-4-piperidyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide and salts and intermediates in the process |
| CZ290517B6 (cs) * | 1996-08-16 | 2002-08-14 | Smithkline Beecham Plc | Způsob přípravy N-[(1-n-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino [3,2-a]indol-10-karboxamidu nebo jeho soli a meziprodukt pro tento způsob |
| GB9618967D0 (en) * | 1996-09-11 | 1996-10-23 | Smithkline Beecham Plc | Pharmaceuticals |
| GB9725933D0 (en) * | 1997-12-05 | 1998-02-04 | Smithkline Beecham Plc | Pharmaceuticals |
| US6277870B1 (en) * | 1998-05-04 | 2001-08-21 | Astra Ab | Use |
| US6251893B1 (en) * | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
| US20020091271A1 (en) | 1998-07-16 | 2002-07-11 | Smithkline Beecham Plc | Process for the preparation of an indole derivative |
| GB9819035D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Res Ltd | Chemical compounds VII |
| EP1112270B1 (en) * | 1998-09-10 | 2007-03-21 | F. Hoffmann-La Roche Ag | Dihydrobenzodioxine carboxamide and ketone derivatives as 5-ht4 receptor antagonists |
| GB9820294D0 (en) * | 1998-09-17 | 1998-11-11 | Smithkline Beecham Plc | Pharmaceuticals |
| US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| US7230000B1 (en) | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
| AU2005203196B9 (en) * | 2000-08-07 | 2009-04-09 | Glaxo Group Limited | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions |
| AU782870C (en) * | 2000-08-07 | 2007-03-15 | Glaxo Group Limited | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions |
| AU782863C (en) * | 2000-08-07 | 2006-08-31 | Glaxo Group Limited | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions |
| PL365048A1 (en) * | 2000-08-07 | 2004-12-27 | Laboratoire Glaxosmithkline S.A.S. | Use of 5ht4 receptor antagonists in the manufacture of a medicament for the prophylaxis or treatment of atrial fibrillation |
| NZ535261A (en) * | 2000-08-08 | 2004-12-24 | Smithkline Beecham P | A tablet comprising the hydrochloride salt of N-(1-nbutyl-4-piperidinyl)methyl]-3,4-[1,3]oxazino[3,2-a] indole-10-carboxamide |
| AU2001276558B2 (en) * | 2000-08-08 | 2005-11-24 | Smithkline Beecham P.L.C. | Pharmaceutical composition comprising condensed indole compound |
| DE60306120T2 (de) * | 2002-02-14 | 2006-11-09 | Glaxo Group Ltd., Greenford | Pharmazeutische formulierung, die n-((1-n-butyl-4-piperidinyl)menthyl)-3,4-dihydro-2h-(1,3)oxazino(3,2-a)indol-10-carboxamid oder ein entsprechendes salz hiervon enthält, sowie deren herstellungsprozess, welcher trockengranulierung beinhaltet |
| EP1480980A4 (en) | 2002-02-15 | 2005-04-20 | Cytokinetics Inc | SYNTHESIS OF QUINAZOLINONES |
| JP2005530785A (ja) | 2002-05-09 | 2005-10-13 | サイトキネティクス・インコーポレーテッド | 化合物、組成物、及び方法 |
| CA2485148A1 (en) | 2002-05-09 | 2003-11-20 | Cytokinetics, Inc. | Pyrimidinone compounds, compositions and methods |
| GB0211230D0 (en) | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| WO2003103575A2 (en) | 2002-05-23 | 2003-12-18 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| US7041676B2 (en) | 2002-06-14 | 2006-05-09 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| JP2006501201A (ja) | 2002-07-23 | 2006-01-12 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
| EP1558083A4 (en) | 2002-09-30 | 2008-04-16 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| ITMI20031468A1 (it) | 2003-07-18 | 2005-01-19 | Acraf | Farmaco ativo nel dolore neuropatico |
| ITMI20031467A1 (it) * | 2003-07-18 | 2005-01-19 | Acraf | Farmaco attivo nel dolore neuropatico |
| EP1692112A4 (en) | 2003-12-08 | 2008-09-24 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS, AND METHODS |
| CA2551171C (en) | 2003-12-23 | 2012-07-10 | Bio-Medisinsk Innovasjon As | Modulators of peripheral 5-ht receptors |
| JP4612301B2 (ja) * | 2003-12-26 | 2011-01-12 | 広栄化学工業株式会社 | １−アルキル−４−アミノメチルピペリジンの製造法 |
| CN101115719B (zh) * | 2004-12-07 | 2011-08-31 | 詹森药业有限公司 | 取代的四环四氢吡喃、吡咯烷和四氢噻吩衍生物 |
| RU2320662C1 (ru) * | 2006-08-24 | 2008-03-27 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ ПИРРОЛО[4,3-b]ИНДОЛЫ, КОМБИНАТОРНАЯ И ФОКУСИРОВАННАЯ БИБЛИОТЕКИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| KR20100024494A (ko) | 2007-06-22 | 2010-03-05 | 아르퀼 인코포레이티드 | 퀴나졸리논 화합물 및 이의 사용 방법 |
| GB0905641D0 (en) * | 2009-04-01 | 2009-05-13 | Serodus As | Compounds |
| WO2021116487A1 (en) | 2019-12-13 | 2021-06-17 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of niemann-pick c disease |
| WO2025077825A1 (en) * | 2023-10-13 | 2025-04-17 | Fauna Bio Incorporated | Methods and compositions for treating cardio-pulmonary disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2557342A1 (de) * | 1975-12-19 | 1977-06-30 | Hoechst Ag | Basisch substituierte indolderivate und verfahren zu ihrer herstellung |
| AU622330B2 (en) * | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
| CA2030051C (en) * | 1989-11-17 | 2001-08-07 | Haruhiko Kikuchi | Indole derivatives |
| US5189041A (en) * | 1990-11-16 | 1993-02-23 | Syntex (U.S.A.) Inc. | Tricyclic 5-ht3 receptor antagonists |
| GB9103862D0 (en) * | 1991-02-25 | 1991-04-10 | Glaxo Group Ltd | Chemical compounds |
| US5206382A (en) * | 1991-06-27 | 1993-04-27 | Fidia Georgetown Institute For The Neurosciences | Indole derivatives, pharmaceutical compositions and methods of treating neurological and psychiatric disorders |
-
1993
- 1993-03-10 AU AU36448/93A patent/AU671102B2/en not_active Expired
- 1993-03-10 SK SK1078-94A patent/SK281423B6/sk not_active IP Right Cessation
- 1993-03-10 RU RU94040864A patent/RU2104279C1/ru not_active IP Right Cessation
- 1993-03-10 WO PCT/GB1993/000506 patent/WO1993018036A1/en not_active Ceased
- 1993-03-10 AT AT98114130T patent/ATE266033T1/de active
- 1993-03-10 ES ES93905561T patent/ES2132223T3/es not_active Expired - Lifetime
- 1993-03-10 AT AT93905561T patent/ATE180785T1/de active
- 1993-03-10 MY MYPI93000436A patent/MY110110A/en unknown
- 1993-03-10 CZ CZ19942210A patent/CZ286194B6/cs not_active IP Right Cessation
- 1993-03-10 DK DK98114130T patent/DK0884319T3/da active
- 1993-03-10 DE DE69333504T patent/DE69333504T2/de not_active Expired - Lifetime
- 1993-03-10 DK DK93905561T patent/DK0630376T3/da active
- 1993-03-10 PT PT98114130T patent/PT884319E/pt unknown
- 1993-03-10 EP EP93905561A patent/EP0630376B1/en not_active Expired - Lifetime
- 1993-03-10 HU HU9402601A patent/HU219121B/hu unknown
- 1993-03-10 NZ NZ249565A patent/NZ249565A/en not_active IP Right Cessation
- 1993-03-10 SG SG1996008846A patent/SG50693A1/en unknown
- 1993-03-10 CA CA2131797A patent/CA2131797C/en not_active Expired - Fee Related
- 1993-03-10 UA UA94095780A patent/UA41311C2/uk unknown
- 1993-03-10 SI SI9300114A patent/SI9300114B/sl active Search and Examination
- 1993-03-10 IL IL10500393A patent/IL105003A/en not_active IP Right Cessation
- 1993-03-10 ES ES98114130T patent/ES2219813T3/es not_active Expired - Lifetime
- 1993-03-10 JP JP5515490A patent/JP2831467B2/ja not_active Expired - Lifetime
- 1993-03-10 AP APAP/P/1993/000494A patent/AP401A/en active
- 1993-03-10 EP EP98114130A patent/EP0884319B1/en not_active Expired - Lifetime
- 1993-03-10 DE DE69325167T patent/DE69325167T2/de not_active Expired - Lifetime
- 1993-03-10 MA MA23113A patent/MA22819A1/fr unknown
- 1993-03-10 KR KR1019940703167A patent/KR100282730B1/ko not_active Expired - Fee Related
- 1993-03-11 CN CN93102648A patent/CN1043893C/zh not_active Expired - Fee Related
- 1993-03-11 MX MX9301348A patent/MX9301348A/es not_active IP Right Cessation
- 1993-05-22 CN CN93107234A patent/CN1085083A/zh active Pending
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1994
- 1994-09-09 NO NO943348A patent/NO303638B1/no not_active IP Right Cessation
- 1994-09-12 FI FI944204A patent/FI107158B/fi not_active IP Right Cessation
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1999
- 1999-06-30 GR GR990401755T patent/GR3030668T3/el unknown
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2005
- 2005-04-12 CY CY0500021A patent/CY2510B1/xx unknown
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Legal Events
| Date | Code | Title | Description |
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| MK4A | Patent expired |
Expiry date: 20130310 |