NO316753B1 - Substituerte aza- og diazacykloheptan og -cyklooktan-forbindelser og deres anvendelser, samt farmasoytiske blandinger inneholdende slike forbindelser - Google Patents

Substituerte aza- og diazacykloheptan og -cyklooktan-forbindelser og deres anvendelser, samt farmasoytiske blandinger inneholdende slike forbindelser Download PDF

Info

Publication number: NO316753B1
Authority: NO; Norway
Prior art keywords: alkyl; phenyl; substituted; compound according; halogen
Prior art date: 1996-01-12

Application number

NO19983187A

Other languages

English (en)

Norwegian (no)

Other versions

NO983187L (no

Inventor

Liliane Unger

Hans-Juergen Teschendorf

Karsten Wicke

Hans-Jorg Treiber

Stefan Blank

Dorothea Starck

Original Assignee

Abbott Gmbh & Co Kg

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.)

1996-01-12

Filing date

1998-07-10

Publication date

2004-04-26

1998-07-10 Application filed by Abbott Gmbh & Co Kg filed Critical Abbott Gmbh & Co Kg

1998-09-09 Publication of NO983187L publication Critical patent/NO983187L/no

2004-04-26 Publication of NO316753B1 publication Critical patent/NO316753B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 64
125000000477 aza group Chemical group 0.000 title description 3
125000000640 cyclooctyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 title description 3
QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical compound C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 title description 3
239000008194 pharmaceutical composition Substances 0.000 title description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
125000002947 alkylene group Chemical group 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
239000000203 mixture Substances 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
-1 ntro Chemical group 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 9
125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
208000035475 disorder Diseases 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
150000007513 acids Chemical class 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 3
229940088353 Dopamine D3 receptor antagonist Drugs 0.000 claims description 2
208000028017 Psychotic disease Diseases 0.000 claims description 2
210000003169 central nervous system Anatomy 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
229940052760 dopamine agonists Drugs 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
239000000018 receptor agonist Substances 0.000 claims description 2
125000004306 triazinyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 1
108010081348 HRT1 protein Hairy Proteins 0.000 claims 1
102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 1
101100258315 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-1 gene Proteins 0.000 claims 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
239000000243 solution Substances 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 8
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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
230000027455 binding Effects 0.000 description 6
229960003638 dopamine Drugs 0.000 description 6
238000000034 method Methods 0.000 description 6
239000012071 phase Substances 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000000126 substance Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
238000004821 distillation Methods 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
239000000047 product Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000007858 starting material Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
108050004812 Dopamine receptor Proteins 0.000 description 4
102000015554 Dopamine receptor Human genes 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000000872 buffer Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000007789 gas Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000005259 measurement Methods 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
150000003230 pyrimidines Chemical class 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
101150049660 DRD2 gene Proteins 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
102000004073 Dopamine D3 Receptors Human genes 0.000 description 3
108090000525 Dopamine D3 Receptors Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
239000000164 antipsychotic agent Substances 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000012467 final product Substances 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
150000002391 heterocyclic compounds Chemical class 0.000 description 3
239000001257 hydrogen Chemical group 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000003446 ligand Substances 0.000 description 3
239000012139 lysis buffer Substances 0.000 description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 2
XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 2
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
ONOBXDPYDHTSBQ-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-diazepine Chemical compound C1CC=CCNN1 ONOBXDPYDHTSBQ-UHFFFAOYSA-N 0.000 description 2
ZSPBHCKOHOVORF-UHFFFAOYSA-N 2-methylsulfonyl-4-phenylmethoxypyrimidine Chemical compound CS(=O)(=O)C1=NC=CC(OCC=2C=CC=CC=2)=N1 ZSPBHCKOHOVORF-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229910004298 SiO 2 Inorganic materials 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000004142 Trypsin Human genes 0.000 description 2
108090000631 Trypsin Proteins 0.000 description 2
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
229940005529 antipsychotics Drugs 0.000 description 2
206010003119 arrhythmia Diseases 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
235000011087 fumaric acid Nutrition 0.000 description 2
239000003365 glass fiber Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
210000003715 limbic system Anatomy 0.000 description 2
238000012417 linear regression Methods 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
239000008188 pellet Substances 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
150000008318 pyrimidones Chemical class 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000001525 receptor binding assay Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
229950001675 spiperone Drugs 0.000 description 2
239000007921 spray Substances 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
238000012360 testing method Methods 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
239000012588 trypsin Substances 0.000 description 2
238000005406 washing Methods 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
WRQMAGMXMIKOLE-UHFFFAOYSA-N 1-[2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl]-1,4-diazepane Chemical compound FC(F)(F)C1=NC(C(C)(C)C)=NC(N2CCNCCC2)=C1 WRQMAGMXMIKOLE-UHFFFAOYSA-N 0.000 description 1
YVYIYAHNEKUDQA-UHFFFAOYSA-N 1-[2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl]-4-(3-chloropropyl)-1,4-diazepane Chemical compound FC(F)(F)C1=NC(C(C)(C)C)=NC(N2CCN(CCCCl)CCC2)=C1 YVYIYAHNEKUDQA-UHFFFAOYSA-N 0.000 description 1
FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical group CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
150000008081 1H-pyrimidin-4-ones Chemical class 0.000 description 1
FNHMJTUQUPQWJN-UHFFFAOYSA-N 2,2-dimethylpropanimidamide Chemical compound CC(C)(C)C(N)=N FNHMJTUQUPQWJN-UHFFFAOYSA-N 0.000 description 1
UXFWTIGUWHJKDD-UHFFFAOYSA-N 2-(4-bromobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCBr)C(=O)C2=C1 UXFWTIGUWHJKDD-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
WBBUUEJEHZWLMW-UHFFFAOYSA-N 2-[4-[4-[2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]butyl]isoindole-1,3-dione Chemical compound FC(F)(F)C1=NC(C(C)(C)C)=NC(N2CCN(CCCCN3C(C4=CC=CC=C4C3=O)=O)CCC2)=C1 WBBUUEJEHZWLMW-UHFFFAOYSA-N 0.000 description 1
OZSKEDYKQXHLRX-UHFFFAOYSA-N 2-methylsulfanyl-4-phenylmethoxypyrimidine Chemical compound CSC1=NC=CC(OCC=2C=CC=CC=2)=N1 OZSKEDYKQXHLRX-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
SCNKFUNWPYDBQX-UHFFFAOYSA-N 2-sulfanyl-3h-thiadiazol-5-amine Chemical compound NC1=CNN(S)S1 SCNKFUNWPYDBQX-UHFFFAOYSA-N 0.000 description 1
PRGHYYFMWHWPRH-UHFFFAOYSA-N 2-tert-butyl-4-chloro-6-(trifluoromethyl)pyrimidine Chemical compound CC(C)(C)C1=NC(Cl)=CC(C(F)(F)F)=N1 PRGHYYFMWHWPRH-UHFFFAOYSA-N 0.000 description 1
GSKVWYTUBVEFEC-UHFFFAOYSA-N 2-tert-butyl-6-(trifluoromethyl)-1h-pyrimidin-4-one Chemical compound CC(C)(C)C1=NC(O)=CC(C(F)(F)F)=N1 GSKVWYTUBVEFEC-UHFFFAOYSA-N 0.000 description 1
RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 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
- C07D403/02—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
- 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
- A61P25/18—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
- 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
- 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

NO19983187A 1996-01-12 1998-07-10 Substituerte aza- og diazacykloheptan og -cyklooktan-forbindelser og deres anvendelser, samt farmasoytiske blandinger inneholdende slike forbindelser NO316753B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19600934A DE19600934A1 (de)	1996-01-12	1996-01-12	Substituierte Aza- und Diazacycloheptan- und Cyclooctanverbindungen und deren Verwendung
PCT/EP1997/000106 WO1997025324A1 (de)	1996-01-12	1997-01-10	Substituierte aza- und diazacycloheptan- und -cyclooctanverbindungen und deren verwendung

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NO983187L NO983187L (no)	1998-09-09
NO316753B1 true NO316753B1 (no)	2004-04-26

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US (2)	US6214822B1 (ko)
EP (1)	EP0877744B1 (ko)
JP (1)	JP4349657B2 (ko)
KR (1)	KR100441073B1 (ko)
CN (2)	CN1075070C (ko)
AR (1)	AR005868A1 (ko)
AT (1)	ATE273301T1 (ko)
AU (1)	AU717726B2 (ko)
BG (1)	BG64098B1 (ko)
CA (1)	CA2241787C (ko)
CO (1)	CO4790173A1 (ko)
CZ (1)	CZ297981B6 (ko)
DE (2)	DE19600934A1 (ko)
ES (1)	ES2225947T3 (ko)
HR (1)	HRP970021A2 (ko)
HU (1)	HU228457B1 (ko)
IL (1)	IL125076A (ko)
MX (1)	MX9805499A (ko)
NO (1)	NO316753B1 (ko)
NZ (1)	NZ326332A (ko)
PL (1)	PL327692A1 (ko)
SK (1)	SK284987B6 (ko)
TR (1)	TR199801302T2 (ko)
TW (1)	TW475929B (ko)
WO (1)	WO1997025324A1 (ko)
ZA (1)	ZA97209B (ko)

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Publication number	Priority date	Publication date	Assignee	Title
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1996
- 1996-01-12 DE DE19600934A patent/DE19600934A1/de not_active Withdrawn
1997
- 1997-01-10 CZ CZ0215998A patent/CZ297981B6/cs not_active IP Right Cessation
- 1997-01-10 PL PL97327692A patent/PL327692A1/xx unknown
- 1997-01-10 AT AT97901000T patent/ATE273301T1/de not_active IP Right Cessation
- 1997-01-10 WO PCT/EP1997/000106 patent/WO1997025324A1/de active IP Right Grant
- 1997-01-10 EP EP97901000A patent/EP0877744B1/de not_active Expired - Lifetime
- 1997-01-10 DE DE59711847T patent/DE59711847D1/de not_active Expired - Lifetime
- 1997-01-10 US US09/101,265 patent/US6214822B1/en not_active Expired - Lifetime
- 1997-01-10 SK SK941-98A patent/SK284987B6/sk not_active IP Right Cessation
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- 1997-01-10 IL IL12507697A patent/IL125076A/en not_active IP Right Cessation
- 1997-01-10 AU AU14407/97A patent/AU717726B2/en not_active Expired
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- 1997-01-10 JP JP52486997A patent/JP4349657B2/ja not_active Expired - Lifetime
- 1997-01-10 KR KR10-1998-0705263A patent/KR100441073B1/ko not_active IP Right Cessation
- 1997-01-10 HR HRP19600934.0A patent/HRP970021A2/hr not_active Application Discontinuation
- 1997-01-10 HU HU9901590A patent/HU228457B1/hu unknown
- 1997-01-10 NZ NZ326332A patent/NZ326332A/en not_active IP Right Cessation
- 1997-01-10 TR TR1998/01302T patent/TR199801302T2/xx unknown
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- 1997-01-10 CA CA002241787A patent/CA2241787C/en not_active Expired - Lifetime
- 1997-01-13 AR ARP970100120A patent/AR005868A1/es not_active Application Discontinuation
- 1997-01-13 TW TW086100296A patent/TW475929B/zh not_active IP Right Cessation
1998
- 1998-07-07 MX MX9805499A patent/MX9805499A/es unknown
- 1998-07-09 BG BG102616A patent/BG64098B1/bg unknown
- 1998-07-10 NO NO19983187A patent/NO316753B1/no not_active IP Right Cessation
2000
- 2000-10-27 US US09/696,941 patent/US6352981B1/en not_active Expired - Lifetime
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Also Published As

Publication number	Publication date
CA2241787C (en)	2006-04-04
JP4349657B2 (ja)	2009-10-21
CZ297981B6 (cs)	2007-05-16
ZA97209B (en)	1998-07-10
AU1440797A (en)	1997-08-01
IL125076A (en)	2001-05-20
DE59711847D1 (de)	2004-09-16
CN1212692A (zh)	1999-03-31
EP0877744B1 (de)	2004-08-11
WO1997025324A1 (de)	1997-07-17
TW475929B (en)	2002-02-11
CN1146551C (zh)	2004-04-21
AU717726B2 (en)	2000-03-30
IL125076A0 (en)	1999-01-26
HRP970021A2 (en)	1998-04-30
CN1075070C (zh)	2001-11-21
MX9805499A (es)	1998-11-30
EP0877744A1 (de)	1998-11-18
KR19990077127A (ko)	1999-10-25
NO983187L (no)	1998-09-09
CZ215998A3 (cs)	1999-05-12
HU228457B1 (en)	2013-03-28
SK284987B6 (sk)	2006-04-06
SK94198A3 (en)	1999-03-12
JP2000505072A (ja)	2000-04-25
DE19600934A1 (de)	1997-07-17
BG64098B1 (bg)	2003-12-31
KR100441073B1 (ko)	2004-11-16
CN1348956A (zh)	2002-05-15
ATE273301T1 (de)	2004-08-15
HUP9901590A3 (en)	2002-01-28
TR199801302T2 (xx)	1998-11-23
ES2225947T3 (es)	2005-03-16
BG102616A (en)	1999-04-30
HUP9901590A2 (hu)	1999-08-30
CA2241787A1 (en)	1997-07-17
US6352981B1 (en)	2002-03-05
AR005868A1 (es)	1999-07-21
NZ326332A (en)	1999-04-29
PL327692A1 (en)	1998-12-21
CO4790173A1 (es)	1999-05-31
US6214822B1 (en)	2001-04-10

Legal Events

Date	Code	Title	Description
2014-06-02	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: ABBVIE DEUTSCHLAND GMBH & CO AG, DE
2017-01-23	MK1K	Patent expired

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