SK286701B6 - Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents

Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie Download PDF

Info

Publication number: SK286701B6
Authority: SK; Slovakia
Prior art keywords: indole; ethyl; piperidin; chloro; methylphenyl
Prior art date: 2000-07-21

Application number

SK203-2003A

Other languages

English (en)

Slovak (sk)

Other versions

SK2032003A3 (en

Inventor

Jakob Felding

Benny Bang-Andersen

Garrick Paul Smith

Kim Andersen

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.)

2000-07-21

Filing date

2001-07-17

Publication date

2009-03-05

2001-07-17 Application filed by H. Lundbeck A/S filed Critical H. Lundbeck A/S

2003-06-03 Publication of SK2032003A3 publication Critical patent/SK2032003A3/sk

2009-03-05 Publication of SK286701B6 publication Critical patent/SK286701B6/sk

Links

150000002475 indoles Chemical class 0.000 title claims abstract description 15
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 14
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims description 8
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims description 8
239000008194 pharmaceutical composition Substances 0.000 title claims description 8
229940054051 antipsychotic indole derivative Drugs 0.000 title claims description 7
201000000980 schizophrenia Diseases 0.000 claims abstract description 12
208000019901 Anxiety disease Diseases 0.000 claims abstract description 9
208000028017 Psychotic disease Diseases 0.000 claims abstract description 9
208000019695 Migraine disease Diseases 0.000 claims abstract description 7
208000010877 cognitive disease Diseases 0.000 claims abstract description 5
230000006872 improvement Effects 0.000 claims abstract description 5
230000007958 sleep Effects 0.000 claims abstract description 5
-1 cyano, nitro amino, hydroxy Chemical group 0.000 claims description 149
125000000217 alkyl group Chemical group 0.000 claims description 58
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
230000000694 effects Effects 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
208000024891 symptom Diseases 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 10
125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 8
229920006395 saturated elastomer Polymers 0.000 claims description 8
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000001072 heteroaryl group Chemical group 0.000 claims description 7
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
230000016571 aggressive behavior Effects 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
239000000164 antipsychotic agent Substances 0.000 claims description 4
229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
208000019906 panic disease Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
SYBVOKCVTYSRPG-UHFFFAOYSA-N n-[3-[2-[4-(5-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C=C(CCN3CCC(CC3)C=3C4=CC(Cl)=CC=C4NC=3)C(C)=CC=2)=C1 SYBVOKCVTYSRPG-UHFFFAOYSA-N 0.000 claims description 3
NUTRIFZDVOBUDS-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=CC=C(C)C(CCN2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)=C1 NUTRIFZDVOBUDS-UHFFFAOYSA-N 0.000 claims description 3
JIRPRUOEKMRRCC-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C(CCN2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)=C1 JIRPRUOEKMRRCC-UHFFFAOYSA-N 0.000 claims description 3
YFLQNIXJLUAWHP-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]morpholine-4-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C)=CC=C1NC(=O)N1CCOCC1 YFLQNIXJLUAWHP-UHFFFAOYSA-N 0.000 claims description 3
BWBNZVJTOUWTRO-UHFFFAOYSA-N n-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]thiophene-2-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=C(Cl)C=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CS1 BWBNZVJTOUWTRO-UHFFFAOYSA-N 0.000 claims description 3
KFKUIMDCNNLHTM-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-4-fluorobenzamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=C(F)C=C1 KFKUIMDCNNLHTM-UHFFFAOYSA-N 0.000 claims description 3
SPOFUJQNHLVFOS-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=C(C)C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)=C1 SPOFUJQNHLVFOS-UHFFFAOYSA-N 0.000 claims description 3
FMOBAHNKNCLUHS-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]benzamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CC=C1 FMOBAHNKNCLUHS-UHFFFAOYSA-N 0.000 claims description 3
GQVIKVMHMCRODW-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]thiadiazole-5-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C1=CN=NS1 GQVIKVMHMCRODW-UHFFFAOYSA-N 0.000 claims description 3
WJQQWWVNJCNWMS-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]thiophene-2-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CS1 WJQQWWVNJCNWMS-UHFFFAOYSA-N 0.000 claims description 3
PLQMWLUVQABXSI-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]thiophene-3-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C=1C=CSC=1 PLQMWLUVQABXSI-UHFFFAOYSA-N 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000003441 thioacyl group Chemical group 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims description 2
SZCVKMOVEPYVAY-UHFFFAOYSA-N 3-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-1-methyl-1-phenylurea Chemical compound C=1C=C(C)C(CCN2CCC(CC2)C=2C3=CC=C(Cl)C=C3NC=2)=CC=1NC(=O)N(C)C1=CC=CC=C1 SZCVKMOVEPYVAY-UHFFFAOYSA-N 0.000 claims description 2
UPWHNYKFYLPTLY-UHFFFAOYSA-N 4-fluoro-n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]benzamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=C(F)C=C1 UPWHNYKFYLPTLY-UHFFFAOYSA-N 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
CSRGGHAQRBPQBW-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)-3,6-dihydro-2h-pyridin-1-yl]ethyl]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C(CCN2CC=C(CC2)C=2C3=CC(F)=CC=C3NC=2)=C1 CSRGGHAQRBPQBW-UHFFFAOYSA-N 0.000 claims description 2
SRAQFFXJBJEVGN-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)-3,6-dihydro-2h-pyridin-1-yl]ethyl]-4-methylphenyl]pyridine-3-carboxamide Chemical compound C1=C(CCN2CC=C(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CN=C1 SRAQFFXJBJEVGN-UHFFFAOYSA-N 0.000 claims description 2
SIJAQKZIQFOKIC-UHFFFAOYSA-N n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]cyclobutanecarboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C)=CC=C1NC(=O)C1CCC1 SIJAQKZIQFOKIC-UHFFFAOYSA-N 0.000 claims description 2
HNCOPUVXUWJJQQ-UHFFFAOYSA-N n-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-2-(4-methoxyphenyl)acetamide Chemical compound C1=CC(OC)=CC=C1CC(=O)NC1=CC=C(C)C(CCN2CCC(CC2)C=2C3=CC=C(Cl)C=C3NC=2)=C1 HNCOPUVXUWJJQQ-UHFFFAOYSA-N 0.000 claims description 2
ROYKPHBDQQUOPT-UHFFFAOYSA-N n-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=CC=C(C)C(CCN2CCC(CC2)C=2C3=CC=C(Cl)C=C3NC=2)=C1 ROYKPHBDQQUOPT-UHFFFAOYSA-N 0.000 claims description 2
GDWYHPJDBGGMAY-UHFFFAOYSA-N n-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]pyridine-3-carboxamide Chemical compound C1=C(CCN2CCC(CC2)C=2C3=CC=C(Cl)C=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CN=C1 GDWYHPJDBGGMAY-UHFFFAOYSA-N 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
GVSMQKKMAYLKMM-UHFFFAOYSA-N 3-chloro-1h-indole Chemical compound C1=CC=C2C(Cl)=CNC2=C1 GVSMQKKMAYLKMM-UHFFFAOYSA-N 0.000 claims 2
150000002431 hydrogen Chemical class 0.000 claims 2
208000013403 hyperactivity Diseases 0.000 claims 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
CTWLIHIEDTYNRM-UHFFFAOYSA-N 4-fluoro-n-[3-[2-[4-(5-fluoro-1h-indol-3-yl)-3,6-dihydro-2h-pyridin-1-yl]ethyl]-4-methylphenyl]benzamide Chemical compound C1=C(CCN2CC=C(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=C(F)C=C1 CTWLIHIEDTYNRM-UHFFFAOYSA-N 0.000 claims 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
XQICOXCELYJLLR-UHFFFAOYSA-N n-[3-[2-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylphenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C=C(CCN3CCC(CC3)C=3C4=CC=C(Cl)C=C4NC=3)C(C)=CC=2)=C1 XQICOXCELYJLLR-UHFFFAOYSA-N 0.000 claims 1
KIXJKVGKALVEBC-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)-3,6-dihydro-2h-pyridin-1-yl]ethyl]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C(CCN2CC=C(CC2)C=2C3=CC=CC(Cl)=C3NC=2)=C1 KIXJKVGKALVEBC-UHFFFAOYSA-N 0.000 claims 1
HCHMGLZVWPQNSZ-UHFFFAOYSA-N n-[3-[2-[4-(7-chloro-1h-indol-3-yl)-3,6-dihydro-2h-pyridin-1-yl]ethyl]-4-methylphenyl]pyridine-3-carboxamide Chemical compound C1=C(CCN2CC=C(CC2)C=2C3=CC=CC(Cl)=C3NC=2)C(C)=CC=C1NC(=O)C1=CC=CN=C1 HCHMGLZVWPQNSZ-UHFFFAOYSA-N 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
206010027599 migraine Diseases 0.000 abstract description 4
208000012902 Nervous system disease Diseases 0.000 abstract description 2
208000025966 Neurological disease Diseases 0.000 abstract description 2
208000020016 psychiatric disease Diseases 0.000 abstract description 2
101000959274 Tenebrio molitor Antidiuretic factor A Proteins 0.000 abstract 1
150000001875 compounds Chemical class 0.000 description 75
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 50
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
108020003175 receptors Proteins 0.000 description 41
102000005962 receptors Human genes 0.000 description 41
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
239000011347 resin Substances 0.000 description 21
229920005989 resin Polymers 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
238000000034 method Methods 0.000 description 18
239000000243 solution Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
LCKMHUXHKGYADQ-UHFFFAOYSA-N 3-[2-[4-(7-chloro-1h-indol-3-yl)piperidin-1-yl]ethyl]-4-methylaniline Chemical compound CC1=CC=C(N)C=C1CCN1CCC(C=2C3=CC=CC(Cl)=C3NC=2)CC1 LCKMHUXHKGYADQ-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
230000029936 alkylation Effects 0.000 description 9
238000005804 alkylation reaction Methods 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
239000003480 eluent Substances 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
239000004793 Polystyrene Substances 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
230000009467 reduction Effects 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
125000004435 hydrogen atom Chemical group [H]* 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
238000010992 reflux Methods 0.000 description 6
235000011054 acetic acid Nutrition 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
230000000561 anti-psychotic effect Effects 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
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125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
229920002223 polystyrene Polymers 0.000 description 5
230000009103 reabsorption Effects 0.000 description 5
239000002464 receptor antagonist Substances 0.000 description 5
229940044551 receptor antagonist Drugs 0.000 description 5
239000011734 sodium Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
JCSRJKWRJVUXSQ-UHFFFAOYSA-N 2-(2-methyl-5-nitrophenyl)acetic acid Chemical compound CC1=CC=C([N+]([O-])=O)C=C1CC(O)=O JCSRJKWRJVUXSQ-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
239000002671 adjuvant Substances 0.000 description 4
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
239000000018 receptor agonist Substances 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
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- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D401/14—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
- 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
- C07D405/14—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 three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- 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

Landscapes

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

SK203-2003A 2000-07-21 2001-07-17 Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie SK286701B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DKPA200001123		2000-07-21
PCT/DK2001/000507 WO2002008223A1 (fr)	2000-07-21	2001-07-17	Derives d'indole utiles dans le traitement de troubles du systeme nerveux central

Publications (2)

Publication Number	Publication Date
SK2032003A3 SK2032003A3 (en)	2003-06-03
SK286701B6 true SK286701B6 (sk)	2009-03-05

Family

ID=8159625

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK203-2003A SK286701B6 (sk)	2000-07-21	2001-07-17	Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie

Country Status (28)

Country	Link
US (1)	US6743809B2 (fr)
EP (1)	EP1305307B1 (fr)
JP (1)	JP2004504396A (fr)
KR (1)	KR100851793B1 (fr)
CN (1)	CN1264838C (fr)
AR (1)	AR029858A1 (fr)
AT (1)	ATE266024T1 (fr)
AU (2)	AU8173801A (fr)
BG (1)	BG107528A (fr)
BR (1)	BR0112998A (fr)
CA (1)	CA2416212C (fr)
CZ (1)	CZ301114B6 (fr)
DE (1)	DE60103162T2 (fr)
EA (1)	EA004749B1 (fr)
ES (1)	ES2219554T3 (fr)
HR (1)	HRP20030015A2 (fr)
HU (1)	HUP0302820A3 (fr)
IL (2)	IL153605A0 (fr)
IS (1)	IS2172B (fr)
MX (1)	MXPA02012927A (fr)
NO (1)	NO323799B1 (fr)
NZ (1)	NZ523436A (fr)
PT (1)	PT1305307E (fr)
SK (1)	SK286701B6 (fr)
TR (1)	TR200401488T4 (fr)
UA (1)	UA73995C2 (fr)
WO (1)	WO2002008223A1 (fr)
ZA (1)	ZA200300287B (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ547314A (en)	2003-11-17	2010-02-26	Boehringer Ingelheim Int	Novel piperidine-substituted indoles- or hetero-derivatives thereof and their use as modulators of chemokine receptor (CCR-3)
TWI391387B (zh) *	2004-05-12	2013-04-01	Eisai R&D Man Co Ltd	具有哌啶環之吲哚衍生物
ATE531706T1 (de)	2005-04-30	2011-11-15	Boehringer Ingelheim Int	Neue piperidin-substituierte indole und ihre verwendung als ccr-3-modulatoren
WO2008049874A1 (fr)	2006-10-27	2008-05-02	Boehringer Ingelheim International Gmbh	Modulateurs ccr3 de pipéridyl-propane-thiol
CN101486654B (zh) *	2009-03-04	2012-10-10	西安近代化学研究所	2-甲基-3-硝基苯乙酸合成方法
CN110041318B (zh) *	2018-01-17	2022-07-29	中国科学院上海药物研究所	一类多巴胺d5受体激动剂及其制备和应用
CN110498789B (zh) *	2018-05-17	2022-04-05	上海医药工业研究院	芳烷哌啶类衍生物及其在多靶点抗抑郁症中的应用

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Publication number	Priority date	Publication date	Assignee	Title
DE2322470A1 (de) *	1973-05-04	1974-11-21	Boehringer Sohn Ingelheim	Neue indolyl-piperidino-(bzw. 1,2,5,6tetrahydro-pyridyl-)butyrophenone und verfahren zu ihrer herstellung
AT332401B (de) *	1973-11-26	1976-09-27	Roussel Uclaf	Verfahren zur herstellung von neuen (4'-(3''-indolyl)-piperidino)-alkylarylketonderivaten
DE3882614T2 (de) *	1987-08-13	1993-11-18	Glaxo Group Ltd	Indol-Derivate.
GB8719167D0 (en) *	1987-08-13	1987-09-23	Glaxo Group Ltd	Chemical compounds
WO1994003444A1 (fr) *	1992-08-05	1994-02-17	John Wyeth & Brother Limited	Derives d'amides
PL311204A1 (en) *	1993-04-22	1996-02-05	Pfizer Res & Dev	Indole derivatives as antagonists of 5-ht-like receptors for use in hemicrania
ES2063700B1 (es) *	1993-04-28	1995-07-16	Vita Invest Sa	Agente activo sobre el sistema nervioso central, proceso para su preparacion y composiciones farmaceuticas que lo contengan.
US5576321A (en) *	1995-01-17	1996-11-19	Eli Lilly And Company	Compounds having effects on serotonin-related systems
GB9718712D0 (en) *	1997-09-03	1997-11-12	Merck Sharp & Dohme	Theraputic Agents

2001
- 2001-07-17 HR HR20030015A patent/HRP20030015A2/hr not_active Application Discontinuation
- 2001-07-17 SK SK203-2003A patent/SK286701B6/sk not_active IP Right Cessation
- 2001-07-17 UA UA2003010167A patent/UA73995C2/uk unknown
- 2001-07-17 CA CA002416212A patent/CA2416212C/fr not_active Expired - Fee Related
- 2001-07-17 AU AU8173801A patent/AU8173801A/xx active Pending
- 2001-07-17 MX MXPA02012927A patent/MXPA02012927A/es active IP Right Grant
- 2001-07-17 KR KR1020037000850A patent/KR100851793B1/ko not_active Expired - Fee Related
- 2001-07-17 HU HU0302820A patent/HUP0302820A3/hu unknown
- 2001-07-17 JP JP2002514129A patent/JP2004504396A/ja active Pending
- 2001-07-17 AU AU2001281738A patent/AU2001281738B2/en not_active Ceased
- 2001-07-17 EA EA200300179A patent/EA004749B1/ru not_active IP Right Cessation
- 2001-07-17 TR TR2004/01488T patent/TR200401488T4/xx unknown
- 2001-07-17 EP EP01960182A patent/EP1305307B1/fr not_active Expired - Lifetime
- 2001-07-17 CN CNB018151078A patent/CN1264838C/zh not_active Expired - Fee Related
- 2001-07-17 CZ CZ20030196A patent/CZ301114B6/cs not_active IP Right Cessation
- 2001-07-17 IL IL15360501A patent/IL153605A0/xx unknown
- 2001-07-17 AT AT01960182T patent/ATE266024T1/de not_active IP Right Cessation
- 2001-07-17 NZ NZ523436A patent/NZ523436A/en unknown
- 2001-07-17 BR BR0112998-8A patent/BR0112998A/pt not_active IP Right Cessation
- 2001-07-17 WO PCT/DK2001/000507 patent/WO2002008223A1/fr not_active Ceased
- 2001-07-17 PT PT01960182T patent/PT1305307E/pt unknown
- 2001-07-17 ES ES01960182T patent/ES2219554T3/es not_active Expired - Lifetime
- 2001-07-17 DE DE60103162T patent/DE60103162T2/de not_active Expired - Fee Related
- 2001-07-20 AR ARP010103457A patent/AR029858A1/es unknown
2002
- 2002-12-23 IS IS6663A patent/IS2172B/is unknown
- 2002-12-24 IL IL153605A patent/IL153605A/en not_active IP Right Cessation
2003
- 2003-01-10 NO NO20030127A patent/NO323799B1/no not_active IP Right Cessation
- 2003-01-10 ZA ZA200300287A patent/ZA200300287B/en unknown
- 2003-01-17 US US10/347,574 patent/US6743809B2/en not_active Expired - Fee Related
- 2003-02-05 BG BG107528A patent/BG107528A/bg unknown

Also Published As

Publication number	Publication date
KR100851793B1 (ko)	2008-08-13
AR029858A1 (es)	2003-07-16
ZA200300287B (en)	2004-03-02
DE60103162D1 (de)	2004-06-09
SK2032003A3 (en)	2003-06-03
US6743809B2 (en)	2004-06-01
CA2416212A1 (fr)	2002-01-31
ATE266024T1 (de)	2004-05-15
CN1451002A (zh)	2003-10-22
IS6663A (is)	2002-12-23
NO323799B1 (no)	2007-07-09
NO20030127D0 (no)	2003-01-10
PT1305307E (pt)	2004-09-30
EA004749B1 (ru)	2004-08-26
EP1305307B1 (fr)	2004-05-06
AU8173801A (en)	2002-02-05
NZ523436A (en)	2004-07-30
CA2416212C (fr)	2007-10-30
US20030166664A1 (en)	2003-09-04
IS2172B (is)	2006-11-15
AU2001281738B2 (en)	2006-12-21
HRP20030015A2 (en)	2005-02-28
MXPA02012927A (es)	2003-05-15
EP1305307A1 (fr)	2003-05-02
CZ301114B6 (cs)	2009-11-11
HK1059782A1 (en)	2004-07-16
IL153605A0 (en)	2003-07-06
UA73995C2 (en)	2005-10-17
EA200300179A1 (ru)	2003-06-26
KR20030017643A (ko)	2003-03-03
JP2004504396A (ja)	2004-02-12
CZ2003196A3 (cs)	2003-05-14
BR0112998A (pt)	2003-06-24
ES2219554T3 (es)	2004-12-01
NO20030127L (no)	2003-01-10
HUP0302820A2 (hu)	2003-12-29
TR200401488T4 (tr)	2004-08-23
BG107528A (bg)	2003-10-31
PL359157A1 (en)	2004-08-23
CN1264838C (zh)	2006-07-19
HUP0302820A3 (en)	2006-04-28
DE60103162T2 (de)	2005-05-04
WO2002008223A1 (fr)	2002-01-31
IL153605A (en)	2008-07-08

Publication	Publication Date	Title
US6958338B2 (en)	2005-10-25	4-,5-,6-and 7-indole derivatives useful for the treatment of CNS disorders
SK286701B6 (sk)	2009-03-05	Indolové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie
AU2001279611A1 (en)	2002-05-30	4-, 5-, 6- and 7-indole derivatives useful for the treatment of CNS disorders
AU2001281738A1 (en)	2002-05-02	Indole derivatives useful for the treatment of cns disorders
WO2003002556A1 (fr)	2003-01-09	Nouveaux derives heteroaryle, preparation et utilisation de ceux-ci
AU2002344949A1 (en)	2003-05-15	Novel heteroaryl derivatives, their preparation and use
EP1468996B1 (fr)	2007-09-26	Derivés d'indole pour le traitement des maladies du système nerveux central
WO2001021614A1 (fr)	2001-03-29	Indoles substitues 5-aminoalkyle et 5-aminocarbonyle
PL203538B1 (pl)	2009-10-30	Podstawiona pochodna indolu i jej zastosowanie oraz kompozycja farmaceutyczna

Legal Events

Date	Code	Title	Description
2010-04-07	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20090717