UA74830C2 - Indole derivatives being useful for the treatment of cns disorders, a pharmaceutical composition and a method for the treatment of diseases - Google Patents
Indole derivatives being useful for the treatment of cns disorders, a pharmaceutical composition and a method for the treatment of diseases Download PDFInfo
- Publication number
- UA74830C2 UA74830C2 UA2002129625A UA2002129625A UA74830C2 UA 74830 C2 UA74830 C2 UA 74830C2 UA 2002129625 A UA2002129625 A UA 2002129625A UA 2002129625 A UA2002129625 A UA 2002129625A UA 74830 C2 UA74830 C2 UA 74830C2
- Authority
- UA
- Ukraine
- Prior art keywords
- dihydro
- indole
- piperidin
- quinolin
- fluoro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 5
- 201000010099 disease Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 17
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 9
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 7
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 206010027599 migraine Diseases 0.000 claims abstract description 6
- 230000007958 sleep Effects 0.000 claims abstract description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 14
- -1 aryl-Cu-alkyl Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 208000024891 symptom Diseases 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 239000000164 antipsychotic agent Substances 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003441 thioacyl 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
- 230000016571 aggressive behavior Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 208000029364 generalized anxiety disease Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 208000019906 panic disease Diseases 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
- 229910052799 carbon Inorganic materials 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
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 229960003638 dopamine Drugs 0.000 abstract description 35
- 239000003446 ligand Substances 0.000 abstract description 13
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 10
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 abstract description 6
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- 230000006872 improvement Effects 0.000 abstract description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 abstract 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000000203 mixture Substances 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 239000003480 eluent Substances 0.000 description 16
- 238000003818 flash chromatography Methods 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- 239000005557 antagonist Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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 12
- 239000012043 crude product Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000005804 alkylation reaction Methods 0.000 description 9
- 230000000561 anti-psychotic effect Effects 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 8
- VQFAITGIMWXQQK-UHFFFAOYSA-N 5-fluoro-3-piperidin-4-yl-1h-indole Chemical compound C12=CC(F)=CC=C2NC=C1C1CCNCC1 VQFAITGIMWXQQK-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
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- 230000029936 alkylation Effects 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
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- 238000009835 boiling Methods 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
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- 238000010992 reflux Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
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- 230000002152 alkylating effect Effects 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
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- 238000012360 testing method Methods 0.000 description 5
- 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
- SBLVUTXZGVPJNG-UHFFFAOYSA-N 1-(5-bromopentyl)-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(CCCCCBr)C(=O)CCC2=C1 SBLVUTXZGVPJNG-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
- CYQAPXIAEFXKPZ-UHFFFAOYSA-N 7-chloro-3-piperidin-4-yl-1h-indole Chemical compound C=1NC=2C(Cl)=CC=CC=2C=1C1CCNCC1 CYQAPXIAEFXKPZ-UHFFFAOYSA-N 0.000 description 4
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- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003860 sleep quality Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- RMWVUWLBLWBQDS-UHFFFAOYSA-N tert-butyl 3-bromopropanoate Chemical compound CC(C)(C)OC(=O)CCBr RMWVUWLBLWBQDS-UHFFFAOYSA-N 0.000 description 1
- KVSNUBKMSMRZEV-UHFFFAOYSA-N tert-butyl 4-(7-chloro-1h-indol-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CNC2=C(Cl)C=CC=C12 KVSNUBKMSMRZEV-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200000919 | 2000-06-14 | ||
| PCT/DK2001/000406 WO2001096328A1 (en) | 2000-06-14 | 2001-06-13 | Indole derivatives useful for the treatment of cns disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA74830C2 true UA74830C2 (en) | 2006-02-15 |
Family
ID=8159557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2002129625A UA74830C2 (en) | 2000-06-14 | 2001-06-13 | Indole derivatives being useful for the treatment of cns disorders, a pharmaceutical composition and a method for the treatment of diseases |
Country Status (10)
| Country | Link |
|---|---|
| CN (1) | CN100415737C (is) |
| BR (1) | BR0111764A (is) |
| EA (1) | EA006315B1 (is) |
| HK (1) | HK1059086A1 (is) |
| IL (2) | IL153234A0 (is) |
| IS (1) | IS6643A (is) |
| PL (1) | PL358967A1 (is) |
| SK (1) | SK402003A3 (is) |
| UA (1) | UA74830C2 (is) |
| ZA (1) | ZA200209958B (is) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA9711376B (en) * | 1996-12-20 | 1998-07-21 | Lundbeck & Co As H | Indole or dihydroindole derivatives |
| GB9825413D0 (en) * | 1998-11-19 | 1999-01-13 | Lilly Co Eli | Pharmaceutical compounds |
-
2001
- 2001-06-13 PL PL01358967A patent/PL358967A1/xx not_active Application Discontinuation
- 2001-06-13 BR BR0111764-5A patent/BR0111764A/pt not_active IP Right Cessation
- 2001-06-13 CN CNB018138101A patent/CN100415737C/zh not_active Expired - Fee Related
- 2001-06-13 UA UA2002129625A patent/UA74830C2/uk unknown
- 2001-06-13 EA EA200300019A patent/EA006315B1/ru not_active IP Right Cessation
- 2001-06-13 IL IL15323401A patent/IL153234A0/xx active IP Right Grant
- 2001-06-13 SK SK40-2003A patent/SK402003A3/sk unknown
-
2002
- 2002-11-29 IS IS6643A patent/IS6643A/is unknown
- 2002-12-03 IL IL153234A patent/IL153234A/en not_active IP Right Cessation
- 2002-12-09 ZA ZA200209958A patent/ZA200209958B/en unknown
-
2004
- 2004-03-22 HK HK04102087.6A patent/HK1059086A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IS6643A (is) | 2002-11-29 |
| ZA200209958B (en) | 2004-06-23 |
| IL153234A (en) | 2007-12-03 |
| EA006315B1 (ru) | 2005-10-27 |
| EA200300019A1 (ru) | 2003-04-24 |
| BR0111764A (pt) | 2003-07-08 |
| IL153234A0 (en) | 2003-07-06 |
| CN1446211A (zh) | 2003-10-01 |
| PL358967A1 (en) | 2004-08-23 |
| SK402003A3 (en) | 2003-07-01 |
| HK1059086A1 (en) | 2004-06-18 |
| CN100415737C (zh) | 2008-09-03 |
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