NO309092B1 - Pyrimido[1,2-a]indoler og pyrimido[1,2-a]indoler til bruk som terapeutikum, legemidler inneholdende forbindelsene, anvendelse av forbindelsene for fremstilling av legemidler samt nye karboksylsyrer - Google Patents
Pyrimido[1,2-a]indoler og pyrimido[1,2-a]indoler til bruk som terapeutikum, legemidler inneholdende forbindelsene, anvendelse av forbindelsene for fremstilling av legemidler samt nye karboksylsyrer Download PDFInfo
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- NO309092B1 NO309092B1 NO971512A NO971512A NO309092B1 NO 309092 B1 NO309092 B1 NO 309092B1 NO 971512 A NO971512 A NO 971512A NO 971512 A NO971512 A NO 971512A NO 309092 B1 NO309092 B1 NO 309092B1
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- Prior art keywords
- compounds
- chain
- carbon atoms
- pyrimido
- straight
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- 239000003814 drug Substances 0.000 title claims description 19
- 229940079593 drug Drugs 0.000 title claims description 13
- HBBKFNCURJQICW-UHFFFAOYSA-N pyrimido[1,2-a]indole Chemical class C1=CC=NC2=CC3=CC=CC=C3N21 HBBKFNCURJQICW-UHFFFAOYSA-N 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 title description 92
- 150000001735 carboxylic acids Chemical class 0.000 title description 7
- 230000001225 therapeutic effect Effects 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000640 cyclooctyl group Chemical group [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 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 238000000034 method Methods 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- -1 for example Chemical class 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 12
- 150000007513 acids Chemical class 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 12
- 102000006991 Apolipoprotein B-100 Human genes 0.000 description 11
- 108010008150 Apolipoprotein B-100 Proteins 0.000 description 11
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- 239000011541 reaction mixture Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000007127 saponification reaction Methods 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 241000416162 Astragalus gummifer Species 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 6
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 229920001615 Tragacanth Polymers 0.000 description 6
- 229950005499 carbon tetrachloride Drugs 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
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- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
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- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
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- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 4
- SORFNYWLKDSNNF-UHFFFAOYSA-N 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine Chemical compound CC1=NC(C)=CC(C=2C(=NC(N)=NN=2)C=2C=CC=CC=2)=C1 SORFNYWLKDSNNF-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
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- OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 description 3
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
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- 238000010521 absorption reaction Methods 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
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- 239000012043 crude product Substances 0.000 description 3
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- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 3
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- 239000011777 magnesium Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- AWTKFTNNPQGGLX-UHFFFAOYSA-N methyl 2-(3-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(C)=C1 AWTKFTNNPQGGLX-UHFFFAOYSA-N 0.000 description 1
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- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
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- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
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- 239000011736 potassium bicarbonate Substances 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
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- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
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- 108010037401 tendamistate Proteins 0.000 description 1
- VQOWAMGSDNVFCV-INIZCTEOSA-N tert-butyl (2s)-2-[4-(bromomethyl)phenyl]-2-cyclopentylacetate Chemical compound C1([C@H](C(=O)OC(C)(C)C)C=2C=CC(CBr)=CC=2)CCCC1 VQOWAMGSDNVFCV-INIZCTEOSA-N 0.000 description 1
- WVUNBBJLJPVTBU-INIZCTEOSA-N tert-butyl (2s)-2-cyclopentyl-2-(4-methylphenyl)acetate Chemical compound C1=CC(C)=CC=C1[C@@H](C(=O)OC(C)(C)C)C1CCCC1 WVUNBBJLJPVTBU-INIZCTEOSA-N 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
- 238000013519 translation Methods 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- DSROZUMNVRXZNO-UHFFFAOYSA-K tris[(1-naphthalen-1-yl-3-phenylnaphthalen-2-yl)oxy]alumane Chemical compound C=1C=CC=CC=1C=1C=C2C=CC=CC2=C(C=2C3=CC=CC=C3C=CC=2)C=1O[Al](OC=1C(=C2C=CC=CC2=CC=1C=1C=CC=CC=1)C=1C2=CC=CC=C2C=CC=1)OC(C(=C1C=CC=CC1=C1)C=2C3=CC=CC=C3C=CC=2)=C1C1=CC=CC=C1 DSROZUMNVRXZNO-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
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- 238000001291 vacuum drying Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19613550A DE19613550A1 (de) | 1996-04-04 | 1996-04-04 | Neue Pyrimido[1,2-a]indole |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO971512D0 NO971512D0 (no) | 1997-04-03 |
| NO971512L NO971512L (no) | 1997-10-06 |
| NO309092B1 true NO309092B1 (no) | 2000-12-11 |
Family
ID=7790502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO971512A NO309092B1 (no) | 1996-04-04 | 1997-04-03 | Pyrimido[1,2-a]indoler og pyrimido[1,2-a]indoler til bruk som terapeutikum, legemidler inneholdende forbindelsene, anvendelse av forbindelsene for fremstilling av legemidler samt nye karboksylsyrer |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US6114341A (fr) |
| EP (1) | EP0799828A3 (fr) |
| JP (1) | JPH1059972A (fr) |
| KR (1) | KR970070008A (fr) |
| CN (2) | CN1067393C (fr) |
| AR (1) | AR006497A1 (fr) |
| AU (1) | AU725786B2 (fr) |
| BG (1) | BG62934B1 (fr) |
| BR (1) | BR9701675A (fr) |
| CA (1) | CA2201434A1 (fr) |
| CO (1) | CO4520306A1 (fr) |
| CZ (1) | CZ102297A3 (fr) |
| DE (1) | DE19613550A1 (fr) |
| DZ (1) | DZ2201A1 (fr) |
| EE (1) | EE9700078A (fr) |
| HN (1) | HN1997000045A (fr) |
| HR (1) | HRP970154A2 (fr) |
| HU (1) | HUP9700708A3 (fr) |
| ID (1) | ID16520A (fr) |
| IL (3) | IL120590A (fr) |
| MA (1) | MA24131A1 (fr) |
| MY (1) | MY126362A (fr) |
| NO (1) | NO309092B1 (fr) |
| NZ (1) | NZ314497A (fr) |
| PE (1) | PE42398A1 (fr) |
| PL (1) | PL319249A1 (fr) |
| SG (1) | SG63698A1 (fr) |
| SK (1) | SK42797A3 (fr) |
| SV (1) | SV1997000025A (fr) |
| TN (1) | TNSN97061A1 (fr) |
| TR (1) | TR199700261A2 (fr) |
| YU (1) | YU12397A (fr) |
| ZA (1) | ZA972829B (fr) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19826469A1 (de) * | 1998-06-13 | 2000-05-25 | Bayer Ag | Verfahren zur Herstellung von 2,4-Dimethylcarbolin und 2,4-Dimethylpyrimido[1,2-a]indol |
| AU2001244635A1 (en) * | 2000-03-30 | 2001-10-15 | Yamanouchi Pharmaceutical Co..Ltd. | Hydrazide derivatives |
| DE10030375A1 (de) * | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| JP4254093B2 (ja) * | 2001-10-17 | 2009-04-15 | 宇部興産株式会社 | ５−ハロゲノインドールの製法 |
| DE10349175A1 (de) * | 2003-10-22 | 2005-05-19 | Bayer Healthcare Ag | Mittel zur Gewichtsreduktion |
| JP5697296B2 (ja) | 2004-03-05 | 2015-04-08 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 高脂血症および高コレステロール血症に関連する障害または疾患を、副作用を最小限にしつつ処置するための方法 |
| AU2005230397B2 (en) * | 2004-04-09 | 2010-04-08 | Elanco Animal Health Ireland Limited | Intermittent dosing regimen for the treatment of overweight with MTP-inhibitors |
| JP5102201B2 (ja) | 2005-05-12 | 2012-12-19 | シー・アール・バード・インコーポレーテッド | 取り外し可能な塞栓血餅フィルタ |
| WO2006129193A2 (fr) * | 2005-05-27 | 2006-12-07 | Pfizer Products Inc. | Polytherapie pour le traitement de l'obesite ou le maintien du poids apres une perte ponderale |
| JP4851522B2 (ja) | 2005-08-09 | 2012-01-11 | シー・アール・バード・インコーポレーテッド | 挿入型血栓フィルタ及びデリバリシステム |
| EP1951224A2 (fr) * | 2005-10-18 | 2008-08-06 | Aegerion Pharmaceuticals | Methodes permettant de traiter les troubles associes a l'hyperlipidemie chez un mammifere |
| WO2007133366A2 (fr) | 2006-05-02 | 2007-11-22 | C. R. Bard, Inc. | Filtre à veine cave formé à partir d'une feuille |
| US20080161279A1 (en) * | 2006-12-21 | 2008-07-03 | Wisler Gerald L | Methods of Treating Obesity |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA718536B (en) * | 1971-01-11 | 1972-09-27 | Wyeth John & Brother Ltd | Heterocyclic compounds |
| DE2200584A1 (de) * | 1971-01-11 | 1972-07-27 | Wyeth John & Brother Ltd | Heterocyclische Verbindungen,Verfahren zu ihrer Herstellung und ihre Verwendung in pharmazeutischen Zubereitungen |
| GB8614246D0 (en) * | 1986-06-11 | 1986-07-16 | Wyeth John & Brother Ltd | Substituted pyrimidoindoles |
| DE4112533A1 (de) * | 1991-04-17 | 1992-10-22 | Bayer Ag | Verfahren zur herstellung von enantiomerenreinen substituierten (chinolin-2-yl-methoxy)phenyl-essigsaeuren |
| DE4200954A1 (de) * | 1991-04-26 | 1992-10-29 | Bayer Ag | Heterocyclisch substituierte phenylessigsaeurederivate |
| US5576342A (en) * | 1992-03-13 | 1996-11-19 | Bayer Aktiengesellschaft | Phenylglycinamides of heterocyclically substitued phenylacetic acid derivatives |
| DE4309968A1 (de) * | 1993-03-26 | 1994-09-29 | Bayer Ag | Phenylglycinamide von heterocyclisch substituierten Phenylessigsäurederivaten |
| DE4208051A1 (de) * | 1992-03-13 | 1993-09-16 | Bayer Ag | Substituierte phenylessigsaeureamide |
| DE4208052A1 (de) * | 1992-03-13 | 1993-09-16 | Bayer Ag | Imidazolyl substituierte phenylessigsaeureamide |
| AU680453B2 (en) * | 1992-11-05 | 1997-07-31 | Smithkline Beecham Plc | Piperidine derivatives as 5-HT4 receptor antagonists |
| DE4302956A1 (de) * | 1993-02-03 | 1994-08-04 | Bayer Ag | Substituierte Imidazo(4,5-b)pyridine und Benzimidazole |
-
1996
- 1996-04-04 DE DE19613550A patent/DE19613550A1/de not_active Withdrawn
-
1997
- 1997-03-17 HR HR19613550.8A patent/HRP970154A2/xx not_active Application Discontinuation
- 1997-03-24 EP EP97104940A patent/EP0799828A3/fr not_active Ceased
- 1997-03-27 AU AU16603/97A patent/AU725786B2/en not_active Ceased
- 1997-03-27 NZ NZ314497A patent/NZ314497A/xx unknown
- 1997-03-31 US US08/829,015 patent/US6114341A/en not_active Expired - Fee Related
- 1997-04-01 YU YU12397A patent/YU12397A/sr unknown
- 1997-04-01 CA CA002201434A patent/CA2201434A1/fr not_active Abandoned
- 1997-04-01 MA MA24544A patent/MA24131A1/fr unknown
- 1997-04-01 SG SG1997001026A patent/SG63698A1/en unknown
- 1997-04-02 PL PL97319249A patent/PL319249A1/xx unknown
- 1997-04-02 IL IL12059097A patent/IL120590A/xx not_active IP Right Cessation
- 1997-04-02 TN TNTNSN97061A patent/TNSN97061A1/fr unknown
- 1997-04-02 ID IDP971112A patent/ID16520A/id unknown
- 1997-04-02 IL IL13164597A patent/IL131645A/xx not_active IP Right Cessation
- 1997-04-02 DZ DZ970048A patent/DZ2201A1/fr active
- 1997-04-02 JP JP9097893A patent/JPH1059972A/ja not_active Withdrawn
- 1997-04-02 BG BG101379A patent/BG62934B1/bg unknown
- 1997-04-02 TR TR97/00261A patent/TR199700261A2/xx unknown
- 1997-04-03 SK SK427-97A patent/SK42797A3/sk unknown
- 1997-04-03 EE EE9700078A patent/EE9700078A/xx unknown
- 1997-04-03 MY MYPI97001435A patent/MY126362A/en unknown
- 1997-04-03 PE PE1997000260A patent/PE42398A1/es not_active Application Discontinuation
- 1997-04-03 NO NO971512A patent/NO309092B1/no not_active IP Right Cessation
- 1997-04-03 ZA ZA9702829A patent/ZA972829B/xx unknown
- 1997-04-03 CO CO97016906A patent/CO4520306A1/es unknown
- 1997-04-03 AR ARP970101336A patent/AR006497A1/es unknown
- 1997-04-03 CZ CZ971022A patent/CZ102297A3/cs unknown
- 1997-04-03 KR KR1019970012342A patent/KR970070008A/ko not_active Application Discontinuation
- 1997-04-04 CN CN97110275A patent/CN1067393C/zh not_active Expired - Fee Related
- 1997-04-04 BR BR9701675A patent/BR9701675A/pt active Search and Examination
- 1997-04-04 HU HU9700708A patent/HUP9700708A3/hu unknown
- 1997-04-04 HN HN1997000045A patent/HN1997000045A/es unknown
- 1997-04-04 SV SV1997000025A patent/SV1997000025A/es unknown
-
1999
- 1999-08-30 IL IL13164599A patent/IL131645A0/xx unknown
-
2000
- 2000-09-12 CN CN00127092A patent/CN1312246A/zh active Pending
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