UA73995C2 - Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment - Google Patents

Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment Download PDF

Info

Publication number: UA73995C2
Authority: UA; Ukraine
Prior art keywords: indole; ethyl; piperidin; chloro; methylphenyl
Prior art date: 2000-07-21

Application number

UA2003010167A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Lundbeck & Co As H

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

2005-10-17

2001-07-17 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

2005-10-17 Publication of UA73995C2 publication Critical patent/UA73995C2/uk

Links

238000000034 method Methods 0.000 title claims description 22
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
150000002475 indoles Chemical class 0.000 title claims description 3
229940054051 antipsychotic indole derivative Drugs 0.000 title claims 2
150000001875 compounds Chemical class 0.000 claims abstract description 88
201000000980 schizophrenia Diseases 0.000 claims abstract description 14
208000028017 Psychotic disease Diseases 0.000 claims abstract description 9
208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
208000019695 Migraine disease Diseases 0.000 claims abstract description 6
208000010877 cognitive disease Diseases 0.000 claims abstract description 5
206010027599 migraine Diseases 0.000 claims abstract description 5
230000007958 sleep Effects 0.000 claims abstract description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 124
-1 cyano, nitro, amino, hydroxy group Chemical group 0.000 claims description 91
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 43
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
230000000694 effects Effects 0.000 claims description 16
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 14
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
208000024891 symptom Diseases 0.000 claims description 12
125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
239000000164 antipsychotic agent Substances 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000001072 heteroaryl group Chemical group 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
229920006395 saturated elastomer Polymers 0.000 claims description 7
208000035475 disorder Diseases 0.000 claims description 6
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
208000011688 Generalised anxiety disease Diseases 0.000 claims description 4
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
230000036506 anxiety Effects 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
208000029364 generalized anxiety disease Diseases 0.000 claims description 4
208000019906 panic disease Diseases 0.000 claims description 4
125000004193 piperazinyl group Chemical group 0.000 claims description 4
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims description 3
ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
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
238000004519 manufacturing process Methods 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 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
125000000168 pyrrolyl 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
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
229960003638 dopamine Drugs 0.000 abstract description 22
239000003446 ligand Substances 0.000 abstract description 7
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 6
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 abstract description 3
208000012902 Nervous system disease Diseases 0.000 abstract description 2
208000025966 Neurological disease Diseases 0.000 abstract description 2
230000006872 improvement Effects 0.000 abstract description 2
208000020016 psychiatric disease Diseases 0.000 abstract description 2
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
239000000203 mixture Substances 0.000 description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 39
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 26
108020003175 receptors Proteins 0.000 description 24
102000005962 receptors Human genes 0.000 description 24
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
229920005989 resin Polymers 0.000 description 21
239000011347 resin Substances 0.000 description 21
239000000243 solution Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
239000005557 antagonist Substances 0.000 description 9
239000003153 chemical reaction reagent Substances 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 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
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
239000003480 eluent Substances 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
230000009467 reduction Effects 0.000 description 8
238000006722 reduction reaction Methods 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
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
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
230000029936 alkylation Effects 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
239000004031 partial agonist Substances 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
239000002904 solvent 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
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 4
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 4
CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000000654 additive Substances 0.000 description 4
230000002152 alkylating effect Effects 0.000 description 4
230000000561 anti-psychotic effect Effects 0.000 description 4
239000012267 brine Substances 0.000 description 4
230000002301 combined effect Effects 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000006396 nitration reaction Methods 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 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
230000002829 reductive effect Effects 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
VHHJXJSFEWEBPU-UHFFFAOYSA-N 2-(2-methyl-5-nitrophenyl)ethyl methanesulfonate Chemical compound CC1=CC=C([N+]([O-])=O)C=C1CCOS(C)(=O)=O VHHJXJSFEWEBPU-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
239000002585 base Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
229910000085 borane Inorganic materials 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000000460 chlorine Chemical group 0.000 description 3
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150000002148 esters Chemical class 0.000 description 3
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239000012948 isocyanate Chemical class 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
239000000725 suspension Substances 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
HKKLOIBMMSAEQY-UHFFFAOYSA-N 2-(2-bromoethyl)-1-methyl-4-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1CCBr HKKLOIBMMSAEQY-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 2
108091005479 5-HT2 receptors Proteins 0.000 description 2
206010001488 Aggression Diseases 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
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YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 2
108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical class [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
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208000012761 aggressive behavior Diseases 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
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230000008485 antagonism Effects 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
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JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 2
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AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
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LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
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MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
239000002245 particle Substances 0.000 description 2
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229960003424 phenylacetic acid Drugs 0.000 description 2
239000003279 phenylacetic acid Substances 0.000 description 2
229910003446 platinum oxide Inorganic materials 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
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QTWBEVAYYDZLQL-UHFFFAOYSA-N thiophene-3-carbonyl chloride Chemical compound ClC(=O)C=1C=CSC=1 QTWBEVAYYDZLQL-UHFFFAOYSA-N 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
238000001665 trituration Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
230000003313 weakening effect Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

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
- 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
- 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
- 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

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical 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)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (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)

UA2003010167A 2000-07-21 2001-07-17 Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment UA73995C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DKPA200001123		2000-07-21
PCT/DK2001/000507 WO2002008223A1 (en)	2000-07-21	2001-07-17	Indole derivatives useful for the treatment of cns disorders

Publications (1)

Publication Number	Publication Date
UA73995C2 true UA73995C2 (en)	2005-10-17

Family

ID=8159625

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2003010167A UA73995C2 (en)	2000-07-21	2001-07-17	Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment

Country Status (28)

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

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2382037C2 (ru)	2003-11-17	2010-02-20	Бёрингер Ингельхайм Интернациональ Гмбх	Новые пиперидинзамещенные индолы или их гетеропроизводные
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
EP2079725B1 (de)	2006-10-27	2011-12-14	Boehringer Ingelheim International GmbH	Piperidylpropanthiole als ccr3-modulatoren
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

Family Cites Families (9)

* Cited by examiner, † Cited by third party
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
AU611469B2 (en) *	1987-08-13	1991-06-13	Glaxo Group Limited	Indole derivatives
GB8719167D0 (en)	1987-08-13	1987-09-23	Glaxo Group Ltd	Chemical compounds
FI950486A0 (fi) *	1992-08-05	1995-02-03	Wyeth John & Brother Ltd	Amidijohdannaiset
KR960701865A (ko) *	1993-04-22	1996-03-28	데이비드 존. 우드	편두통에 사용하는 5-HT1 유사 효능제인 인돌 유도체(Indole Derivatives as 5-HT, -Like Agonists for Use in Migraine)
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 IL IL15360501A patent/IL153605A0/xx unknown
- 2001-07-17 ES ES01960182T patent/ES2219554T3/es not_active Expired - Lifetime
- 2001-07-17 HR HR20030015A patent/HRP20030015A2/hr not_active Application Discontinuation
- 2001-07-17 AU AU8173801A patent/AU8173801A/xx active Pending
- 2001-07-17 CZ CZ20030196A patent/CZ301114B6/cs not_active IP Right Cessation
- 2001-07-17 KR KR1020037000850A patent/KR100851793B1/ko not_active Expired - Fee Related
- 2001-07-17 MX MXPA02012927A patent/MXPA02012927A/es active IP Right Grant
- 2001-07-17 AT AT01960182T patent/ATE266024T1/de not_active IP Right Cessation
- 2001-07-17 SK SK203-2003A patent/SK286701B6/sk not_active IP Right Cessation
- 2001-07-17 EA EA200300179A patent/EA004749B1/ru not_active IP Right Cessation
- 2001-07-17 BR BR0112998-8A patent/BR0112998A/pt not_active IP Right Cessation
- 2001-07-17 WO PCT/DK2001/000507 patent/WO2002008223A1/en not_active Ceased
- 2001-07-17 TR TR2004/01488T patent/TR200401488T4/xx unknown
- 2001-07-17 AU AU2001281738A patent/AU2001281738B2/en not_active Ceased
- 2001-07-17 EP EP01960182A patent/EP1305307B1/de not_active Expired - Lifetime
- 2001-07-17 HU HU0302820A patent/HUP0302820A3/hu unknown
- 2001-07-17 JP JP2002514129A patent/JP2004504396A/ja active Pending
- 2001-07-17 NZ NZ523436A patent/NZ523436A/en unknown
- 2001-07-17 PT PT01960182T patent/PT1305307E/pt unknown
- 2001-07-17 UA UA2003010167A patent/UA73995C2/uk unknown
- 2001-07-17 CN CNB018151078A patent/CN1264838C/zh not_active Expired - Fee Related
- 2001-07-17 DE DE60103162T patent/DE60103162T2/de not_active Expired - Fee Related
- 2001-07-17 CA CA002416212A patent/CA2416212C/en 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 ZA ZA200300287A patent/ZA200300287B/en unknown
- 2003-01-10 NO NO20030127A patent/NO323799B1/no not_active IP Right Cessation
- 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
EA200300179A1 (ru)	2003-06-26
CZ301114B6 (cs)	2009-11-11
IS2172B (is)	2006-11-15
BG107528A (bg)	2003-10-31
EP1305307A1 (de)	2003-05-02
SK2032003A3 (en)	2003-06-03
HUP0302820A3 (en)	2006-04-28
EP1305307B1 (de)	2004-05-06
IS6663A (is)	2002-12-23
JP2004504396A (ja)	2004-02-12
NZ523436A (en)	2004-07-30
WO2002008223A1 (en)	2002-01-31
PL359157A1 (en)	2004-08-23
EA004749B1 (ru)	2004-08-26
TR200401488T4 (tr)	2004-08-23
NO323799B1 (no)	2007-07-09
SK286701B6 (sk)	2009-03-05
NO20030127L (no)	2003-01-10
KR100851793B1 (ko)	2008-08-13
IL153605A (en)	2008-07-08
ZA200300287B (en)	2004-03-02
AR029858A1 (es)	2003-07-16
PT1305307E (pt)	2004-09-30
ES2219554T3 (es)	2004-12-01
AU8173801A (en)	2002-02-05
US6743809B2 (en)	2004-06-01
DE60103162D1 (de)	2004-06-09
HRP20030015A2 (en)	2005-02-28
BR0112998A (pt)	2003-06-24
ATE266024T1 (de)	2004-05-15
KR20030017643A (ko)	2003-03-03
DE60103162T2 (de)	2005-05-04
MXPA02012927A (es)	2003-05-15
CN1451002A (zh)	2003-10-22
NO20030127D0 (no)	2003-01-10
CN1264838C (zh)	2006-07-19
CA2416212A1 (en)	2002-01-31
US20030166664A1 (en)	2003-09-04
HK1059782A1 (en)	2004-07-16
IL153605A0 (en)	2003-07-06
CZ2003196A3 (cs)	2003-05-14
HUP0302820A2 (hu)	2003-12-29
CA2416212C (en)	2007-10-30
AU2001281738B2 (en)	2006-12-21

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