ZA200209886B - Indole derivatives useful for the treatment of CNS disorders. - Google Patents
Indole derivatives useful for the treatment of CNS disorders. Download PDFInfo
- Publication number
- ZA200209886B ZA200209886B ZA200209886A ZA200209886A ZA200209886B ZA 200209886 B ZA200209886 B ZA 200209886B ZA 200209886 A ZA200209886 A ZA 200209886A ZA 200209886 A ZA200209886 A ZA 200209886A ZA 200209886 B ZA200209886 B ZA 200209886B
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- ZA
- South Africa
- Prior art keywords
- chr
- compound according
- bound
- indole
- dihydro
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims description 13
- 150000002475 indoles Chemical class 0.000 title claims description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 208000015114 central nervous system disease Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 105
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 14
- 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 13
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
- -1 cyano, nitro, amino, hydroxy Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- NQENZDVUTKEFAQ-UHFFFAOYSA-N 1-[3-[4-(1h-indol-5-yl)piperazin-1-yl]propyl]-3,4-dihydro-2h-quinoline Chemical compound C1CCC2=CC=CC=C2N1CCCN1CCN(C=2C=C3C=CNC3=CC=2)CC1 NQENZDVUTKEFAQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 125000003441 thioacyl group Chemical group 0.000 claims description 5
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 239000000164 antipsychotic agent Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- CBMAIWIEVGZLEF-UHFFFAOYSA-N 1-(3,4-dihydro-1h-isoquinolin-2-yl)-3-[4-(1h-indol-5-yl)piperazin-1-yl]propan-1-one Chemical compound C1CC2=CC=CC=C2CN1C(=O)CCN1CCN(C=2C=C3C=CNC3=CC=2)CC1 CBMAIWIEVGZLEF-UHFFFAOYSA-N 0.000 claims description 2
- 208000011688 Generalised anxiety disease Diseases 0.000 claims description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
- 230000016571 aggressive behavior Effects 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 208000019906 panic disease Diseases 0.000 claims description 2
- 230000007958 sleep Effects 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- 108020003175 receptors Proteins 0.000 description 31
- 102000005962 receptors Human genes 0.000 description 31
- 238000000034 method Methods 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 22
- 229960003638 dopamine Drugs 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 229960001866 silicon dioxide Drugs 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- MZILCLREQQTZJP-UHFFFAOYSA-N 5-piperazin-1-yl-1h-indole Chemical compound C1CNCCN1C1=CC=C(NC=C2)C2=C1 MZILCLREQQTZJP-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 230000002152 alkylating effect Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
- MZLUUIRCZKORFY-UHFFFAOYSA-N 1-(3-bromopropyl)-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(CCCBr)C(=O)CCC2=C1 MZLUUIRCZKORFY-UHFFFAOYSA-N 0.000 description 4
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 229910000086 alane Inorganic materials 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 4
- 230000000561 anti-psychotic effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UGMBIAPMJXMUOS-UHFFFAOYSA-N 5-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indole Chemical compound C1NCCC(C=2C=C3C=CNC3=CC=2)=C1 UGMBIAPMJXMUOS-UHFFFAOYSA-N 0.000 description 3
- DEEIDJWDLYITNC-UHFFFAOYSA-N 6-piperazin-1-yl-1h-indole Chemical compound C1CNCCN1C1=CC=C(C=CN2)C2=C1 DEEIDJWDLYITNC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000003962 Dopamine D4 receptors Human genes 0.000 description 3
- 108090000357 Dopamine D4 receptors Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000004031 partial agonist Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NHQHUBOLAKEMOP-UHFFFAOYSA-N 1-(2-chloroethyl)-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(CCCl)C(=O)CCC2=C1 NHQHUBOLAKEMOP-UHFFFAOYSA-N 0.000 description 2
- NXZMDUDFNVIZTH-UHFFFAOYSA-N 1-[3-[4-(1h-indol-5-yl)piperazin-1-yl]propyl]-3,4-dihydroquinolin-2-one Chemical compound C1=C2NC=CC2=CC(N2CCN(CC2)CCCN2C3=CC=CC=C3CCC2=O)=C1 NXZMDUDFNVIZTH-UHFFFAOYSA-N 0.000 description 2
- WUKQSLPBSUSULJ-UHFFFAOYSA-N 2-(2-oxo-3,4-dihydroquinolin-1-yl)ethyl acetate Chemical compound C1=CC=C2N(CCOC(=O)C)C(=O)CCC2=C1 WUKQSLPBSUSULJ-UHFFFAOYSA-N 0.000 description 2
- YWPMKTWUFVOFPL-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(=O)NCCC2=C1 YWPMKTWUFVOFPL-UHFFFAOYSA-N 0.000 description 2
- APVCUPXGTOKIRN-UHFFFAOYSA-N 4-bromo-1-(3,4-dihydro-1h-isoquinolin-2-yl)butan-1-one Chemical compound C1=CC=C2CN(C(=O)CCCBr)CCC2=C1 APVCUPXGTOKIRN-UHFFFAOYSA-N 0.000 description 2
- ULMINHJMQWBDGD-UHFFFAOYSA-N 5-piperidin-4-yl-1h-indole Chemical class C1CNCCC1C1=CC=C(NC=C2)C2=C1 ULMINHJMQWBDGD-UHFFFAOYSA-N 0.000 description 2
- 206010001488 Aggression Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical class C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 2
- 229960005417 ketanserin Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000010807 negative regulation of binding Effects 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 2
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- 239000012312 sodium hydride Substances 0.000 description 2
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
- 229950001675 spiperone Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
- HRGUFAFCJCSWKF-UHFFFAOYSA-N 1-(3,4-dihydro-1h-isoquinolin-2-yl)-4-[4-(1h-indol-5-yl)piperazin-1-yl]butan-1-one Chemical compound C1CC2=CC=CC=C2CN1C(=O)CCCN1CCN(C=2C=C3C=CNC3=CC=2)CC1 HRGUFAFCJCSWKF-UHFFFAOYSA-N 0.000 description 1
- FWTGMJKTXCFLEL-UHFFFAOYSA-N 1-(4-bromobutyl)-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(CCCCBr)C(=O)CCC2=C1 FWTGMJKTXCFLEL-UHFFFAOYSA-N 0.000 description 1
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- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Toxicology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200001018 | 2000-06-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200209886B true ZA200209886B (en) | 2003-12-05 |
Family
ID=8159589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200209886A ZA200209886B (en) | 2000-06-29 | 2002-12-05 | Indole derivatives useful for the treatment of CNS disorders. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20030232822A1 (zh) |
| EP (1) | EP1299380B1 (zh) |
| JP (1) | JP2004501912A (zh) |
| KR (1) | KR20030011365A (zh) |
| CN (1) | CN1439004A (zh) |
| AR (1) | AR028736A1 (zh) |
| AT (1) | ATE268765T1 (zh) |
| AU (1) | AU2001273882A1 (zh) |
| BG (1) | BG107471A (zh) |
| BR (1) | BR0112286A (zh) |
| CA (1) | CA2414115A1 (zh) |
| CZ (1) | CZ20024192A3 (zh) |
| DE (1) | DE60103761D1 (zh) |
| EA (1) | EA200300084A1 (zh) |
| HU (1) | HUP0300786A2 (zh) |
| IL (1) | IL153254A0 (zh) |
| IS (1) | IS6642A (zh) |
| MX (1) | MXPA02012506A (zh) |
| NO (1) | NO20026029L (zh) |
| PL (1) | PL358966A1 (zh) |
| SK (1) | SK1092003A3 (zh) |
| WO (1) | WO2002000645A1 (zh) |
| ZA (1) | ZA200209886B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0117577D0 (en) * | 2001-02-16 | 2001-09-12 | Aventis Pharm Prod Inc | Novel heterocyclic substituted carbonyl derivatives and their use as dopamine D receptor ligands |
| AU2003257407A1 (en) * | 2002-08-29 | 2004-03-19 | H. Lundbeck A/S | S-(+)-3-{1-(2-(2,3-dihydro-1h-indol-3-yl)ethyl)-3,6-dihydro-2h-pyridin-4-yl}-6-chloro-1h-indole and acid addition salts thereof |
| DE102004027358A1 (de) | 2004-06-04 | 2005-12-29 | Abbott Gmbh & Co. Kg | Pyrimidinverbindungen und ihre Verwendung |
| AU2007281591A1 (en) | 2006-07-31 | 2008-02-07 | Janssen Pharmaceutica, N.V. | Urotensin II receptor antagonists |
| SE531698C2 (sv) | 2007-07-12 | 2009-07-07 | Respiratorius Ab | Nya bronkdilaterande a,b-omättade amider |
| FR2953839A1 (fr) * | 2009-12-14 | 2011-06-17 | Sanofi Aventis | Nouveaux derives d'(heterocycle-piperidine condensee)-(piperazinyl)-1alcanone ou d'(heterocycle-pyrrolidine condensee)-(piperazinyl)-1alcanone et leur utilisation comme inhibiteurs de p75 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL310443A1 (en) * | 1993-03-01 | 1995-12-11 | Merck Sharp & Dohme | Derivatives of pyrolo-pyridine |
| ZA9711376B (en) * | 1996-12-20 | 1998-07-21 | Lundbeck & Co As H | Indole or dihydroindole derivatives |
-
2001
- 2001-06-13 IL IL15325401A patent/IL153254A0/xx unknown
- 2001-06-13 AT AT01940241T patent/ATE268765T1/de not_active IP Right Cessation
- 2001-06-13 JP JP2002505393A patent/JP2004501912A/ja not_active Withdrawn
- 2001-06-13 BR BR0112286-0A patent/BR0112286A/pt not_active Application Discontinuation
- 2001-06-13 MX MXPA02012506A patent/MXPA02012506A/es unknown
- 2001-06-13 AU AU2001273882A patent/AU2001273882A1/en not_active Abandoned
- 2001-06-13 WO PCT/DK2001/000407 patent/WO2002000645A1/en not_active Application Discontinuation
- 2001-06-13 KR KR1020027017614A patent/KR20030011365A/ko not_active Application Discontinuation
- 2001-06-13 HU HU0300786A patent/HUP0300786A2/hu unknown
- 2001-06-13 PL PL01358966A patent/PL358966A1/xx not_active Application Discontinuation
- 2001-06-13 CA CA002414115A patent/CA2414115A1/en not_active Abandoned
- 2001-06-13 CZ CZ20024192A patent/CZ20024192A3/cs unknown
- 2001-06-13 EP EP01940241A patent/EP1299380B1/en not_active Expired - Lifetime
- 2001-06-13 CN CN01811847A patent/CN1439004A/zh active Pending
- 2001-06-13 EA EA200300084A patent/EA200300084A1/ru unknown
- 2001-06-13 SK SK109-2003A patent/SK1092003A3/sk unknown
- 2001-06-13 DE DE60103761T patent/DE60103761D1/de not_active Expired - Fee Related
- 2001-06-19 AR ARP010102901A patent/AR028736A1/es unknown
-
2002
- 2002-11-29 IS IS6642A patent/IS6642A/is unknown
- 2002-12-05 ZA ZA200209886A patent/ZA200209886B/en unknown
- 2002-12-16 NO NO20026029A patent/NO20026029L/no not_active Application Discontinuation
- 2002-12-17 US US10/327,670 patent/US20030232822A1/en not_active Abandoned
-
2003
- 2003-01-17 BG BG107471A patent/BG107471A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA02012506A (es) | 2003-04-25 |
| AR028736A1 (es) | 2003-05-21 |
| CZ20024192A3 (cs) | 2003-04-16 |
| IL153254A0 (en) | 2003-07-06 |
| BG107471A (en) | 2003-10-31 |
| IS6642A (is) | 2002-11-29 |
| SK1092003A3 (en) | 2003-05-02 |
| US20030232822A1 (en) | 2003-12-18 |
| NO20026029D0 (no) | 2002-12-16 |
| CA2414115A1 (en) | 2002-01-03 |
| PL358966A1 (en) | 2004-08-23 |
| EA200300084A1 (ru) | 2003-06-26 |
| WO2002000645A1 (en) | 2002-01-03 |
| EP1299380B1 (en) | 2004-06-09 |
| EP1299380A1 (en) | 2003-04-09 |
| DE60103761D1 (de) | 2004-07-15 |
| JP2004501912A (ja) | 2004-01-22 |
| AU2001273882A1 (en) | 2002-01-08 |
| ATE268765T1 (de) | 2004-06-15 |
| NO20026029L (no) | 2002-12-16 |
| KR20030011365A (ko) | 2003-02-07 |
| BR0112286A (pt) | 2003-05-13 |
| CN1439004A (zh) | 2003-08-27 |
| HUP0300786A2 (hu) | 2003-07-28 |
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