ES2383369T3 - Sales de succinato y malonato de TRANS-4-((1R,3S)-6-CLORO-3-FENILINDAN-1-IL)-1,2,2-TRIMETILPIPERAZINA y el uso como medicamento - Google Patents

Sales de succinato y malonato de TRANS-4-((1R,3S)-6-CLORO-3-FENILINDAN-1-IL)-1,2,2-TRIMETILPIPERAZINA y el uso como medicamento Download PDF

Info

Publication number: ES2383369T3
Authority: ES; Spain
Prior art keywords: compound; salt; formula; hydrogen; malonate
Prior art date: 2003-08-18
Legal status (The legal status 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 status listed.): Expired - Lifetime

Application number

ES04762772T

Other languages

English (en)

Spanish (es)

Inventor

Heidi Lopez De Diego

Ole Nielsen

Lone Munch Ringgard

Henrik Svane

Allan Carsten Dahl

Mark Howells

Benny Bang-Andersen

Lars Ole Lyngso

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

H Lundbeck AS

Original Assignee

H Lundbeck AS

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.)

2003-08-18

Filing date

2004-08-18

Publication date

2012-06-20

2004-08-18 Application filed by H Lundbeck AS filed Critical H Lundbeck AS

2004-08-18 Priority claimed from PCT/DK2004/000545 external-priority patent/WO2005016900A1/en

2012-06-20 Application granted granted Critical

2012-06-20 Publication of ES2383369T3 publication Critical patent/ES2383369T3/es

2024-08-18 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

150000003839 salts Chemical class 0.000 title claims description 92
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical class [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 title claims description 14
239000003814 drug Substances 0.000 title claims description 9
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical class [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 title description 11
150000001875 compounds Chemical class 0.000 claims abstract description 255
150000002690 malonic acid derivatives Chemical class 0.000 claims abstract description 22
150000003890 succinate salts Chemical class 0.000 claims abstract description 20
238000000034 method Methods 0.000 claims description 59
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 55
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 48
239000002904 solvent Substances 0.000 claims description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 25
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 25
230000002255 enzymatic effect Effects 0.000 claims description 25
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 24
-1 ex. Cl or Br Chemical class 0.000 claims description 21
238000006243 chemical reaction Methods 0.000 claims description 19
201000000980 schizophrenia Diseases 0.000 claims description 19
239000012458 free base Substances 0.000 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
239000000843 powder Substances 0.000 claims description 16
238000002360 preparation method Methods 0.000 claims description 16
208000028017 Psychotic disease Diseases 0.000 claims description 14
208000024891 symptom Diseases 0.000 claims description 13
201000010099 disease Diseases 0.000 claims description 11
KDYFGRWQOYBRFD-UHFFFAOYSA-M succinate(1-) Chemical compound OC(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-M 0.000 claims description 11
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 10
230000005855 radiation Effects 0.000 claims description 10
BYPMJBXPNZMNQD-PZJWPPBQSA-N Zicronapine Chemical compound C1C(C)(C)N(C)CCN1[C@H]1C2=CC(Cl)=CC=C2[C@H](C=2C=CC=CC=2)C1 BYPMJBXPNZMNQD-PZJWPPBQSA-N 0.000 claims description 8
PIPWSBOFSUJCCO-UHFFFAOYSA-N 2,2-dimethylpiperazine Chemical compound CC1(C)CNCCN1 PIPWSBOFSUJCCO-UHFFFAOYSA-N 0.000 claims description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 7
208000020925 Bipolar disease Diseases 0.000 claims description 5
206010026749 Mania Diseases 0.000 claims description 5
239000002585 base Substances 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
OFOBLEOULBTSOW-UHFFFAOYSA-M malonate(1-) Chemical compound OC(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-M 0.000 claims description 5
208000021465 Brief psychotic disease Diseases 0.000 claims description 4
208000024254 Delusional disease Diseases 0.000 claims description 4
208000027089 Parkinsonian disease Diseases 0.000 claims description 4
206010034010 Parkinsonism Diseases 0.000 claims description 4
208000019568 Shared Paranoid disease Diseases 0.000 claims description 4
208000028810 Shared psychotic disease Diseases 0.000 claims description 4
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
238000002955 isolation Methods 0.000 claims description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
239000003176 neuroleptic agent Substances 0.000 claims description 4
230000000701 neuroleptic effect Effects 0.000 claims description 4
208000002851 paranoid schizophrenia Diseases 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
208000022610 schizoaffective disease Diseases 0.000 claims description 4
208000007848 Alcoholism Diseases 0.000 claims description 3
208000019901 Anxiety disease Diseases 0.000 claims description 3
206010012335 Dependence Diseases 0.000 claims description 3
206010054089 Depressive symptom Diseases 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
208000019022 Mood disease Diseases 0.000 claims description 3
150000001335 aliphatic alkanes Chemical group 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 claims description 3
239000000945 filler Substances 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
206010027599 migraine Diseases 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
150000003335 secondary amines Chemical class 0.000 claims description 3
BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 claims description 2
208000022497 Cocaine-Related disease Diseases 0.000 claims description 2
206010057852 Nicotine dependence Diseases 0.000 claims description 2
229930040373 Paraformaldehyde Natural products 0.000 claims description 2
208000025569 Tobacco Use disease Diseases 0.000 claims description 2
125000003158 alcohol group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
201000006145 cocaine dependence Diseases 0.000 claims description 2
206010013663 drug dependence Diseases 0.000 claims description 2
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
230000011987 methylation Effects 0.000 claims description 2
238000007069 methylation reaction Methods 0.000 claims description 2
229920002866 paraformaldehyde Polymers 0.000 claims description 2
238000006268 reductive amination reaction Methods 0.000 claims description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 3
150000007524 organic acids Chemical class 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 1
229910052740 iodine Inorganic materials 0.000 claims 1
239000000203 mixture Substances 0.000 description 65
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
230000015572 biosynthetic process Effects 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
239000000243 solution Substances 0.000 description 30
238000003786 synthesis reaction Methods 0.000 description 29
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
238000005917 acylation reaction Methods 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
230000010933 acylation Effects 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
239000002244 precipitate Substances 0.000 description 15
239000000725 suspension Substances 0.000 description 15
239000008346 aqueous phase Substances 0.000 description 13
239000000460 chlorine Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000007787 solid Substances 0.000 description 12
230000020176 deacylation Effects 0.000 description 11
238000005947 deacylation reaction Methods 0.000 description 11
229910052739 hydrogen Inorganic materials 0.000 description 11
239000001257 hydrogen Substances 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
239000012071 phase Substances 0.000 description 11
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 10
229910052717 sulfur Inorganic materials 0.000 description 10
102000004190 Enzymes Human genes 0.000 description 9
108090000790 Enzymes Proteins 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000000113 differential scanning calorimetry Methods 0.000 description 9
150000002431 hydrogen Chemical class 0.000 description 9
239000001384 succinic acid Substances 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
238000001914 filtration Methods 0.000 description 8
229960004592 isopropanol Drugs 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000000047 product Substances 0.000 description 8
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
229910052802 copper Inorganic materials 0.000 description 7
239000010949 copper Substances 0.000 description 7
239000012535 impurity Substances 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
238000001556 precipitation Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
RFAPOGMFZTYBEW-UHFFFAOYSA-N 1,2,2-trimethylpiperazine Chemical compound CN1CCNCC1(C)C RFAPOGMFZTYBEW-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
108090001060 Lipase Proteins 0.000 description 6
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102000004882 Lipase Human genes 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000012467 final product Substances 0.000 description 6
235000019421 lipase Nutrition 0.000 description 6
238000000634 powder X-ray diffraction Methods 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
ZBFIRYWCOIYJDA-UHFFFAOYSA-N 3,3-dimethylpiperazin-2-one Chemical compound CC1(C)NCCNC1=O ZBFIRYWCOIYJDA-UHFFFAOYSA-N 0.000 description 5
102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 5
108091005479 5-HT2 receptors Proteins 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
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230000008025 crystallization Effects 0.000 description 5
238000001514 detection method Methods 0.000 description 5
239000012971 dimethylpiperazine Substances 0.000 description 5
239000007789 gas Substances 0.000 description 5
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239000012453 solvate Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
NVZAYUDBSXWJKD-ZFWWWQNUSA-N (1s,3s)-6-chloro-3-phenyl-2,3-dihydro-1h-inden-1-ol Chemical compound C1([C@@H]2C[C@@H](C3=CC(Cl)=CC=C32)O)=CC=CC=C1 NVZAYUDBSXWJKD-ZFWWWQNUSA-N 0.000 description 4
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
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238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000013067 intermediate product Substances 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
230000008569 process Effects 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
MZYSFGBQMMGPIL-DZGCQCFKSA-N (1s,3r)-3,5-dichloro-1-phenyl-2,3-dihydro-1h-indene Chemical compound C1([C@@H]2C[C@H](C3=CC(Cl)=CC=C32)Cl)=CC=CC=C1 MZYSFGBQMMGPIL-DZGCQCFKSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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102000017910 Adrenergic receptor Human genes 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
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239000002671 adjuvant Substances 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
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239000012267 brine Substances 0.000 description 3
238000004296 chiral HPLC Methods 0.000 description 3
230000009849 deactivation Effects 0.000 description 3
238000001962 electrophoresis Methods 0.000 description 3
238000003821 enantio-separation Methods 0.000 description 3
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239000002245 particle Substances 0.000 description 3
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229910000033 sodium borohydride Inorganic materials 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
UAIVFDJJMVMUGY-UHFFFAOYSA-N 1,2,4-trimethylpiperazine Chemical compound CC1CN(C)CCN1C UAIVFDJJMVMUGY-UHFFFAOYSA-N 0.000 description 2
OVBFMEVBMNZIBR-UHFFFAOYSA-M 2-methylvalerate Chemical compound CCCC(C)C([O-])=O OVBFMEVBMNZIBR-UHFFFAOYSA-M 0.000 description 2
UUYMYRKAVSCKOJ-UHFFFAOYSA-N 3,3,4-trimethylpiperazin-2-one Chemical compound CN1CCNC(=O)C1(C)C UUYMYRKAVSCKOJ-UHFFFAOYSA-N 0.000 description 2
IGIDLTISMCAULB-UHFFFAOYSA-N 3-methylvaleric acid Chemical compound CCC(C)CC(O)=O IGIDLTISMCAULB-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
BYPMJBXPNZMNQD-FPOVZHCZSA-N 4-[(1s,3s)-6-chloro-3-phenyl-2,3-dihydro-1h-inden-1-yl]-1,2,2-trimethylpiperazine Chemical compound C1C(C)(C)N(C)CCN1[C@@H]1C2=CC(Cl)=CC=C2[C@H](C=2C=CC=CC=2)C1 BYPMJBXPNZMNQD-FPOVZHCZSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
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- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
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- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
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- C07C35/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings
- C07C35/32—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings the condensed ring system being a (4.3.0) system, e.g. indenols
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- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
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- C12P7/00—Preparation of oxygen-containing organic compounds
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ES04762772T 2003-08-18 2004-08-18 Sales de succinato y malonato de TRANS-4-((1R,3S)-6-CLORO-3-FENILINDAN-1-IL)-1,2,2-TRIMETILPIPERAZINA y el uso como medicamento Expired - Lifetime ES2383369T3 (es)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
US49605803P	2003-08-18	2003-08-18
DKPA200301180		2003-08-18
DK200301180		2003-08-18
US496058P		2003-08-18
DK200301305		2003-09-11
DKPA200301305		2003-09-11
US52024603P	2003-11-14	2003-11-14
US520246P		2003-11-14
PCT/DK2004/000545 WO2005016900A1 (en)	2003-08-18	2004-08-18	Succinate and malonate salt of trans-4-(ir,3s)-6-chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and the use as a medicament

Publications (1)

Publication Number	Publication Date
ES2383369T3 true ES2383369T3 (es)	2012-06-20

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ES04762772T Expired - Lifetime ES2383369T3 (es)	2003-08-18	2004-08-18	Sales de succinato y malonato de TRANS-4-((1R,3S)-6-CLORO-3-FENILINDAN-1-IL)-1,2,2-TRIMETILPIPERAZINA y el uso como medicamento

Country Status (15)

Country	Link
KR (2)	KR20060066104A (sr)
CN (1)	CN101935305B (sr)
AR (2)	AR045278A1 (sr)
AT (1)	ATE552247T1 (sr)
DK (1)	DK1658277T3 (sr)
EA (2)	EA014641B1 (sr)
ES (1)	ES2383369T3 (sr)
IS (1)	IS8264A (sr)
ME (1)	MEP2408A (sr)
MY (2)	MY149089A (sr)
PT (1)	PT1658277E (sr)
RS (3)	RS53369B (sr)
SG (2)	SG148183A1 (sr)
SI (1)	SI1658277T1 (sr)
TW (2)	TWI388550B (sr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TWI453198B (zh) *	2005-02-16	2014-09-21	Lundbeck & Co As H	製造反式-1-((1r,3s)-6-氯基-3-苯基茚滿-1-基) -3 , 3 -二甲基六氫吡與其鹽類之方法及製造4-((1r , 3s）-6 -氯基-3-苯基茚滿-1-基 )-1,2,2-三甲基六氫吡與其鹽類之方法
SI3135656T1 (sl)	2011-06-20	2019-05-31	H. Lundbeck A/S	Devterirani 1-piperazino-3-fenil indani za zdravljenje shizofrenije
KR20220023333A (ko)	2019-04-11	2022-03-02	메이 파마, 아이엔씨.	보루시클립 다형체 및 그의 제조 및 사용 방법

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE50867B1 (en) *	1980-02-29	1986-08-06	Kefalas As	Indane derivatives
DK55192D0 (da) *	1992-04-28	1992-04-28	Lundbeck & Co As H	1-piperazino-1,2-dihydroindenderivater

2004
- 2004-08-18 RS RS20060121A patent/RS53369B/sr unknown
- 2004-08-18 KR KR1020067003357A patent/KR20060066104A/ko not_active Withdrawn
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- 2004-08-18 AT AT04762772T patent/ATE552247T1/de active
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- 2004-08-18 AR ARP040102966A patent/AR045278A1/es not_active Application Discontinuation
- 2004-08-18 CN CN2010101632528A patent/CN101935305B/zh not_active Expired - Fee Related
- 2004-08-18 SI SI200431885T patent/SI1658277T1/sl unknown
- 2004-08-18 RS YUP-2006/0121A patent/RS20060121A/sr unknown
- 2004-08-18 DK DK04762772.4T patent/DK1658277T3/da active
- 2004-08-18 SG SG200808521-9A patent/SG148183A1/en unknown
- 2004-08-18 AR ARP040102967A patent/AR045279A1/es not_active Application Discontinuation
- 2004-08-18 TW TW093124784A patent/TWI388550B/zh not_active IP Right Cessation
- 2004-08-18 EA EA200600443A patent/EA200600443A1/ru unknown
- 2004-08-18 KR KR1020067003177A patent/KR101227789B1/ko not_active Expired - Fee Related
- 2004-08-18 SG SG200805893-5A patent/SG145723A1/en unknown
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- 2004-08-18 MY MYPI20082882A patent/MY154535A/en unknown
- 2004-08-18 RS YUP-2006/0083A patent/RS20060083A/sr unknown
- 2004-08-18 ES ES04762772T patent/ES2383369T3/es not_active Expired - Lifetime
2006
- 2006-01-26 IS IS8264A patent/IS8264A/is unknown

Also Published As

Publication number	Publication date
SG148183A1 (en)	2008-12-31
EA200600441A1 (ru)	2006-08-25
HK1096089A1 (en)	2007-05-25
PT1658277E (pt)	2012-05-25
TWI388550B (zh)	2013-03-11
EA200600443A1 (ru)	2006-08-25
ATE552247T1 (de)	2012-04-15
TW200519098A (en)	2005-06-16
MEP2408A (xx)	2010-02-10
TWI403505B (zh)	2013-08-01
SI1658277T1 (sl)	2012-10-30
EA014641B1 (ru)	2010-12-30
KR101227789B1 (ko)	2013-01-30
MY149089A (en)	2013-07-15
KR20060066104A (ko)	2006-06-15
IS8264A (is)	2006-01-26
RS20060121A (sr)	2008-09-29
TW201111351A (en)	2011-04-01
HK1152699A1 (en)	2012-03-09
RS20060083A (sr)	2008-08-07
AR045279A1 (es)	2005-10-19
MY154535A (en)	2015-06-30
AR045278A1 (es)	2005-10-19
RS53369B (sr)	2014-10-31
SG145723A1 (en)	2008-09-29
CN101935305A (zh)	2011-01-05
DK1658277T3 (da)	2012-06-18
CN101935305B (zh)	2013-04-10
KR20060066094A (ko)	2006-06-15

Publication	Publication Date	Title
AU2010206058B2 (en)	2012-05-17	Succinate and malonate salt of trans-4-(1R,3S)-6-chloro-3-Phenylindan-1-yl)-1,2,2-trimethylpiperazine and their use as a medicament
BRPI0607438A2 (pt)	2010-04-06	métodos para fabricar um composto e para a conversão de composto ivb enantiomericamente enriquecido em composto iv essencialmente racêmico, e, composto
ES2383369T3 (es)	2012-06-20	Sales de succinato y malonato de TRANS-4-((1R,3S)-6-CLORO-3-FENILINDAN-1-IL)-1,2,2-TRIMETILPIPERAZINA y el uso como medicamento
ES2368786T3 (es)	2011-11-22	Base cristalina de trans-1-((1r,3s)-6-cloro-3-fenilindan-1-il)-3,3-dimetilpiperazina.
CN1839124B (zh)	2010-06-16	反式-4-((1r,3s)-6-氯-3-苯基茚满-1-基)-1,2,2-三甲基哌嗪的琥珀酸盐和丙二酸盐,及其作为药物的用途
HK1152699B (en)	2013-08-30	Method for preparing trans-4-((1r,3s)-6-chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and the salts thereof and the intermediates used therein
HK1096089B (en)	2011-02-02	Succinate and malonate salt of trans-4-(ir,3s)-6-chloro-3-phenylindan-1-yl)-1,2,2-trimethylpiperazine and the use as a medicament