BG107611A - 4-, 5-, 6- и 7- индолови производни използвани залечение разстройства на централната нервна система - Google Patents

4-, 5-, 6- и 7- индолови производни използвани залечение разстройства на централната нервна система Download PDF

Info

Publication number: BG107611A
Authority: BG; Bulgaria
Prior art keywords: methyl; indole; piperazin; alkyl; group
Prior art date: 2000-08-18

Application number

BG107611A

Other languages

Bulgarian (bg)

English (en)

Inventor

Benny Bang-Andersen

Jan Kehler

Original Assignee

H.Lundbeck A/S

Priority date (The priority date 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 date listed.)

2000-08-18

Filing date

2003-03-06

Publication date

2003-12-31

2003-03-06 Application filed by H.Lundbeck A/S filed Critical H.Lundbeck A/S

2003-12-31 Publication of BG107611A publication Critical patent/BG107611A/bg

Links

229940054051 antipsychotic indole derivative Drugs 0.000 title description 2
-1 methylene dioxy group Chemical group 0.000 claims abstract description 109
150000001875 compounds Chemical class 0.000 claims abstract description 63
125000002252 acyl group Chemical group 0.000 claims abstract description 13
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
150000002367 halogens Chemical class 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
125000001041 indolyl group Chemical group 0.000 claims abstract description 11
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims abstract description 11
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
125000003118 aryl group Chemical group 0.000 claims abstract description 10
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 10
125000001424 substituent group Chemical group 0.000 claims abstract description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 6
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 5
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 5
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims abstract description 5
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 4
125000003441 thioacyl group Chemical group 0.000 claims abstract description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 13
125000000217 alkyl group Chemical group 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 11
208000028017 Psychotic disease Diseases 0.000 claims description 8
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
201000000980 schizophrenia Diseases 0.000 claims description 8
208000024891 symptom Diseases 0.000 claims description 8
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 7
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 7
239000003085 diluting agent Substances 0.000 claims description 6
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
208000012661 Dyskinesia Diseases 0.000 claims description 5
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 5
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 5
BDKHNYRNYWKAIO-UHFFFAOYSA-N 5-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(OC)=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1 BDKHNYRNYWKAIO-UHFFFAOYSA-N 0.000 claims description 4
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
TWAMSXHFGNOVLT-UHFFFAOYSA-N 5-[(4-phenylpiperazin-1-yl)methyl]-1h-indole Chemical compound C=1C=C2NC=CC2=CC=1CN(CC1)CCN1C1=CC=CC=C1 TWAMSXHFGNOVLT-UHFFFAOYSA-N 0.000 claims description 3
JYNBMOGITRKBBH-UHFFFAOYSA-N 6-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(Cl)=CC=C1N1CCN(CC=2C=C3NC=CC3=CC=2)CC1 JYNBMOGITRKBBH-UHFFFAOYSA-N 0.000 claims description 3
QZASZNJFIZLJFJ-UHFFFAOYSA-N 6-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(OC)=CC=C1N1CCN(CC=2C=C3NC=CC3=CC=2)CC1 QZASZNJFIZLJFJ-UHFFFAOYSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
230000007278 cognition impairment Effects 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
229920006395 saturated elastomer Polymers 0.000 claims description 3
BQEZHLDXTUPRJN-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(F)=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1 BQEZHLDXTUPRJN-UHFFFAOYSA-N 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
FYBDIIFFALWSQI-UHFFFAOYSA-N 4-[4-(1h-indol-5-ylmethyl)piperazin-1-yl]phenol;5-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(O)=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1.COC1=CC=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1 FYBDIIFFALWSQI-UHFFFAOYSA-N 0.000 claims 1
AQLXZGBHDKWNMS-UHFFFAOYSA-N 5-[[4-(3,4-dimethoxyphenyl)piperazin-1-yl]methyl]-1h-indole;5-[[4-(3-methoxyphenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound COC1=CC=CC(N2CCN(CC=3C=C4C=CNC4=CC=3)CC2)=C1.C1=C(OC)C(OC)=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1 AQLXZGBHDKWNMS-UHFFFAOYSA-N 0.000 claims 1
LBSDMKOUXCJRJQ-UHFFFAOYSA-N 5-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-indole 5-[4-(1H-indol-5-ylmethyl)piperazin-1-yl]-1H-indole Chemical compound N1C=CC2=CC(=CC=C12)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=CC=C(C=C1)N1CCN(CC1)CC=1C=C2C=CNC2=CC1 LBSDMKOUXCJRJQ-UHFFFAOYSA-N 0.000 claims 1
FPEYKUGYCPBUGB-UHFFFAOYSA-N ClC1=CC=C(C=C1)N1CCN(CC1)CC1=CC=C2C=CN(C2=C1)C.ClC1=CC=C(C=C1)N1CCN(CC1)CC=1C=C2C=CN(C2=CC1)C Chemical compound ClC1=CC=C(C=C1)N1CCN(CC1)CC1=CC=C2C=CN(C2=C1)C.ClC1=CC=C(C=C1)N1CCN(CC1)CC=1C=C2C=CN(C2=CC1)C FPEYKUGYCPBUGB-UHFFFAOYSA-N 0.000 claims 1
HVKCXZKBKJNOMS-UHFFFAOYSA-N ClC=1C=C(C=CC1)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=C(C=CC=C1)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=CC=C(C=C1)C1CCN(CC1)CC=1C=C2C=CNC2=CC1 Chemical compound ClC=1C=C(C=CC1)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=C(C=CC=C1)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=CC=C(C=C1)C1CCN(CC1)CC=1C=C2C=CNC2=CC1 HVKCXZKBKJNOMS-UHFFFAOYSA-N 0.000 claims 1
NYBBBKYOORNLFA-UHFFFAOYSA-N ClC=1C=C(C=CC1Cl)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CC=1C=C2C=CNC2=CC1 Chemical compound ClC=1C=C(C=CC1Cl)N1CCN(CC1)CC=1C=C2C=CNC2=CC1.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CC=1C=C2C=CNC2=CC1 NYBBBKYOORNLFA-UHFFFAOYSA-N 0.000 claims 1
125000003282 alkyl amino group Chemical group 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
230000019771 cognition Effects 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
208000035475 disorder Diseases 0.000 claims 1
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 44
229960003638 dopamine Drugs 0.000 abstract description 22
239000003446 ligand Substances 0.000 abstract description 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 5
125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 abstract description 3
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
238000000034 method Methods 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000000243 solution Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
230000000694 effects Effects 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
239000000654 additive Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000002464 receptor antagonist Substances 0.000 description 6
229940044551 receptor antagonist Drugs 0.000 description 6
239000002253 acid Substances 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
239000000203 mixture Substances 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 4
LFXXDQVEFFXFSD-UHFFFAOYSA-N 5-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(Cl)=CC=C1N1CCN(CC=2C=C3C=CNC3=CC=2)CC1 LFXXDQVEFFXFSD-UHFFFAOYSA-N 0.000 description 4
208000018737 Parkinson disease Diseases 0.000 description 4
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150000001412 amines Chemical class 0.000 description 4
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GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 4
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
239000007787 solid Substances 0.000 description 4
BQDJABPCSJJOJJ-UHFFFAOYSA-N 5-[[4-(4-methylphenyl)piperidin-1-yl]methyl]-1h-indole Chemical compound C1=CC(C)=CC=C1C1CCN(CC=2C=C3C=CNC3=CC=2)CC1 BQDJABPCSJJOJJ-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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239000004480 active ingredient Substances 0.000 description 3
208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
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239000008120 corn starch Substances 0.000 description 3
229940099112 cornstarch Drugs 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
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235000019359 magnesium stearate Nutrition 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
239000004031 partial agonist Substances 0.000 description 3
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239000002904 solvent Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
125000001544 thienyl group Chemical group 0.000 description 3
FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
KRVOJOCLBAAKSJ-RDTXWAMCSA-N (2R,3R)-nemonapride Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C(=O)N[C@H]1[C@@H](C)N(CC=2C=CC=CC=2)CC1 KRVOJOCLBAAKSJ-RDTXWAMCSA-N 0.000 description 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 2
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JTSKVZMBTOWELA-UHFFFAOYSA-N 5-[[4-(2,3-dichlorophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound ClC1=CC=CC(N2CCN(CC=3C=C4C=CNC4=CC=3)CC2)=C1Cl JTSKVZMBTOWELA-UHFFFAOYSA-N 0.000 description 2
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Classifications

- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

BG107611A 2000-08-18 2003-03-06 4-, 5-, 6- и 7- индолови производни използвани залечение разстройства на централната нервна система BG107611A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DKPA200001229		2000-08-18
PCT/DK2001/000547 WO2002016349A1 (fr)	2000-08-18	2001-08-17	Derives 4-, 5-, 6- et 7-indoliques utiles dans le traitement de troubles du systeme nerveux central

Publications (1)

Publication Number	Publication Date
BG107611A true BG107611A (bg)	2003-12-31

Family

ID=8159658

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107611A BG107611A (bg)	2000-08-18	2003-03-06	4-, 5-, 6- и 7- индолови производни използвани залечение разстройства на централната нервна система

Country Status (29)

Country	Link
US (2)	US6958338B2 (fr)
EP (1)	EP1309586B1 (fr)
JP (1)	JP2004506731A (fr)
KR (1)	KR20030022363A (fr)
CN (1)	CN1243750C (fr)
AR (1)	AR030357A1 (fr)
AT (1)	ATE321040T1 (fr)
AU (2)	AU2001279611B2 (fr)
BG (1)	BG107611A (fr)
BR (1)	BR0113452A (fr)
CA (1)	CA2419266A1 (fr)
CZ (1)	CZ2003461A3 (fr)
DE (1)	DE60118205T2 (fr)
DK (1)	DK1309586T3 (fr)
EA (1)	EA006155B1 (fr)
ES (1)	ES2257424T3 (fr)
HR (1)	HRP20030052A2 (fr)
HU (1)	HUP0302777A2 (fr)
IL (1)	IL154051A0 (fr)
IS (1)	IS6694A (fr)
MX (1)	MXPA03000838A (fr)
NO (1)	NO20030522L (fr)
NZ (1)	NZ523786A (fr)
PL (1)	PL363309A1 (fr)
PT (1)	PT1309586E (fr)
SK (1)	SK3212003A3 (fr)
UA (1)	UA74837C2 (fr)
WO (1)	WO2002016349A1 (fr)
ZA (1)	ZA200300562B (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2520567A3 (fr) *	2006-02-23	2012-12-12	Shionogi & Co., Ltd.	Dérivés d'hétérocycle contenant de l'azote substitués avec un groupe cyclique
US7645789B2 (en)	2006-04-07	2010-01-12	Vertex Pharmaceuticals Incorporated	Indole derivatives as CFTR modulators
JP5420395B2 (ja)	2006-04-07	2014-02-19	バーテックスファーマシューティカルズインコーポレイテッド	Ａｔｐ結合カセット輸送体の調節剤
USRE50453E1 (en)	2006-04-07	2025-06-10	Vertex Pharmaceuticals Incorporated	Indole derivatives as CFTR modulators
US10022352B2 (en)	2006-04-07	2018-07-17	Vertex Pharmaceuticals Incorporated	Modulators of ATP-binding cassette transporters
US8563573B2 (en)	2007-11-02	2013-10-22	Vertex Pharmaceuticals Incorporated	Azaindole derivatives as CFTR modulators
TWI404702B (zh) *	2007-08-31	2013-08-11	Lundbeck & Co As H	兒茶酚胺衍生物和其前藥
US8802868B2 (en)	2010-03-25	2014-08-12	Vertex Pharmaceuticals Incorporated	Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide
RU2569678C2 (ru)	2010-04-22	2015-11-27	Вертекс Фармасьютикалз Инкорпорейтед	Способ получения циклоалкилкарбоксамидо-индольных соединений
AU2013290444B2 (en)	2012-07-16	2018-04-26	Vertex Pharmaceuticals Incorporated	Pharmaceutical compositions of (R)-1-(2,2-diflurorbenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide and administration thereof
JO3425B1 (ar)	2013-07-15	2019-10-20	Novartis Ag	مشتقات البابيريدينيل-اندول واستخدامها كعامل متمم لمثبطات b
PL3925607T5 (pl)	2014-04-15	2026-06-01	Vertex Pharmaceuticals Incorporated	Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3421641A1 (de) *	1984-06-09	1985-12-12	Merck Patent Gmbh, 6100 Darmstadt	Indolderivate
MX173362B (es) *	1987-03-02	1994-02-23	Pfizer	Compuestos de piperazinil heterociclicos y procedimiento para su preparacion
US4831031A (en) *	1988-01-22	1989-05-16	Pfizer Inc.	Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity
US5576336A (en) *	1993-03-18	1996-11-19	Merck Sharp & Dohme Limited	Indole derivatives as dopamine D4 antagonists
EP0757686A1 (fr) *	1994-04-28	1997-02-12	MERCK SHARP & DOHME LTD.	Derives de benzofurane utilises comme antagonistes du recepteur d 4?
DE19500689A1 (de) *	1995-01-12	1996-07-18	Merck Patent Gmbh	Indolpiperidin-Derivate
GB9520731D0 (en) *	1995-10-10	1995-12-13	Merck Sharp & Dohme	Therapeutic agents
GB9604036D0 (en) *	1996-02-26	1996-04-24	Merck Sharp & Dohme	Therapeutic agents
YU47600A (sh) *	1998-01-27	2002-09-19	Aventis Pharmaceuticals Products Inc.	SUPSTITUISANI OKSOAZAHETEROCIKLIL INHIBITORI FAKTORA Xa
WO2001029025A2 (fr) *	1999-10-19	2001-04-26	Merck & Co., Inc.	Inhibiteurs de tyrosine kinases
US6727264B1 (en) *	2001-07-05	2004-04-27	Synaptic Pharmaceutical Corporation	Substituted anilinic piperidines as MCH selective antagonists

2001
- 2001-08-15 AR ARP010103899A patent/AR030357A1/es not_active Application Discontinuation
- 2001-08-17 JP JP2002521450A patent/JP2004506731A/ja not_active Withdrawn
- 2001-08-17 EA EA200300278A patent/EA006155B1/ru not_active IP Right Cessation
- 2001-08-17 CN CNB018142400A patent/CN1243750C/zh not_active Expired - Fee Related
- 2001-08-17 CA CA002419266A patent/CA2419266A1/fr not_active Abandoned
- 2001-08-17 DE DE60118205T patent/DE60118205T2/de not_active Expired - Fee Related
- 2001-08-17 PT PT01957788T patent/PT1309586E/pt unknown
- 2001-08-17 EP EP01957788A patent/EP1309586B1/fr not_active Expired - Lifetime
- 2001-08-17 KR KR10-2003-7001687A patent/KR20030022363A/ko not_active Ceased
- 2001-08-17 HR HR20030052A patent/HRP20030052A2/xx not_active Application Discontinuation
- 2001-08-17 UA UA2003010504A patent/UA74837C2/uk unknown
- 2001-08-17 HU HU0302777A patent/HUP0302777A2/hu unknown
- 2001-08-17 WO PCT/DK2001/000547 patent/WO2002016349A1/fr not_active Ceased
- 2001-08-17 AU AU2001279611A patent/AU2001279611B2/en not_active Ceased
- 2001-08-17 SK SK321-2003A patent/SK3212003A3/sk unknown
- 2001-08-17 IL IL15405101A patent/IL154051A0/xx unknown
- 2001-08-17 CZ CZ2003461A patent/CZ2003461A3/cs unknown
- 2001-08-17 DK DK01957788T patent/DK1309586T3/da active
- 2001-08-17 NZ NZ523786A patent/NZ523786A/en unknown
- 2001-08-17 AT AT01957788T patent/ATE321040T1/de not_active IP Right Cessation
- 2001-08-17 ES ES01957788T patent/ES2257424T3/es not_active Expired - Lifetime
- 2001-08-17 BR BR0113452-3A patent/BR0113452A/pt not_active IP Right Cessation
- 2001-08-17 MX MXPA03000838A patent/MXPA03000838A/es active IP Right Grant
- 2001-08-17 PL PL01363309A patent/PL363309A1/xx not_active Application Discontinuation
- 2001-08-17 AU AU7961101A patent/AU7961101A/xx active Pending
2003
- 2003-01-20 IS IS6694A patent/IS6694A/is unknown
- 2003-01-21 ZA ZA200300562A patent/ZA200300562B/en unknown
- 2003-02-03 NO NO20030522A patent/NO20030522L/no not_active Application Discontinuation
- 2003-02-04 US US10/359,052 patent/US6958338B2/en not_active Expired - Fee Related
- 2003-03-06 BG BG107611A patent/BG107611A/bg unknown
2005
- 2005-09-01 US US11/219,544 patent/US7105543B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP1309586B1 (fr)	2006-03-22
AR030357A1 (es)	2003-08-20
DE60118205D1 (de)	2006-05-11
HUP0302777A2 (hu)	2003-12-29
EP1309586A1 (fr)	2003-05-14
MXPA03000838A (es)	2003-06-06
NO20030522D0 (no)	2003-02-03
EA200300278A1 (ru)	2003-06-26
AU2001279611B2 (en)	2006-08-10
SK3212003A3 (en)	2003-07-01
KR20030022363A (ko)	2003-03-15
NZ523786A (en)	2005-07-29
EA006155B1 (ru)	2005-10-27
JP2004506731A (ja)	2004-03-04
HRP20030052A2 (en)	2005-02-28
US7105543B2 (en)	2006-09-12
PL363309A1 (en)	2004-11-15
CN1243750C (zh)	2006-03-01
AU7961101A (en)	2002-03-04
IL154051A0 (en)	2003-07-31
PT1309586E (pt)	2006-06-30
NO20030522L (no)	2003-02-03
CZ2003461A3 (cs)	2003-05-14
US20030166665A1 (en)	2003-09-04
IS6694A (is)	2003-01-20
ZA200300562B (en)	2004-08-23
WO2002016349A1 (fr)	2002-02-28
BR0113452A (pt)	2003-07-15
HK1059438A1 (en)	2004-07-02
DE60118205T2 (de)	2006-11-02
CN1447806A (zh)	2003-10-08
ES2257424T3 (es)	2006-08-01
CA2419266A1 (fr)	2002-02-28
ATE321040T1 (de)	2006-04-15
US6958338B2 (en)	2005-10-25
DK1309586T3 (da)	2006-07-10
UA74837C2 (en)	2006-02-15
US20060004022A1 (en)	2006-01-05

Publication	Publication Date	Title
SK9342003A3 (en)	2003-10-07	3-Indoline derivatives useful in the treatment of psychiatric and neurologic disorders
EP1309586B1 (fr)	2006-03-22	Derives 4-, 5-, 6- et 7-indoliques utiles dans le traitement de troubles du systeme nerveux central
AU2001279611A1 (en)	2002-05-30	4-, 5-, 6- and 7-indole derivatives useful for the treatment of CNS disorders
US6890916B2 (en)	2005-05-10	Indole derivatives useful for the treatment of CNS disorders
AU2001273881A1 (en)	2002-03-14	Indole derivatives useful for the treatment of CNS disorders
SK286701B6 (sk)	2009-03-05	Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie
AU2001281738A1 (en)	2002-05-02	Indole derivatives useful for the treatment of cns disorders
SK1092003A3 (en)	2003-05-02	Indole derivatives useful for the treatment of CNS disorders
EP1468996B1 (fr)	2007-09-26	Derivés d'indole pour le traitement des maladies du système nerveux central
MXPA02012568A (es)	2003-04-10	Derivados de indol utiles para el tratameinto de enfermedades del sistema nervioso central.
EP1214312A1 (fr)	2002-06-19	Indoles substitues 5-aminoalkyle et 5-aminocarbonyle
SK402003A3 (en)	2003-07-01	Indole derivatives, pharmaceutical composition comprising same and their use
MXPA02012149A (en)	2008-10-03	Indole derivatives useful for the treatment of cns disorders