SK42797A3 - Pyrido£1,2-a|indoles, process for their production, pharmauceutical compositions containing said substances, intermediate products for their production and their use - Google Patents

Pyrido£1,2-a|indoles, process for their production, pharmauceutical compositions containing said substances, intermediate products for their production and their use Download PDF

Info

Publication number: SK42797A3
Authority: SK; Slovakia
Prior art keywords: group; straight; carbon atoms; branched; optionally substituted
Prior art date: 1996-04-04

Application number

SK427-97A

Other languages

English (en)

Slovak (sk)

Inventor

Ulrich Muller

Peter Eckenberg

Rudi Grutzmann

Hilmar Bischoff

Dirk Denzer

Stefan Wohlfeil

Stefan Lohmer

Ulrich Nielsch

Peter Kolkhof

Original Assignee

Bayer Ag

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.)

1996-04-04

Filing date

1997-04-03

Publication date

1997-11-05

1997-04-03 Application filed by Bayer Ag filed Critical Bayer Ag

1997-11-05 Publication of SK42797A3 publication Critical patent/SK42797A3/sk

Links

238000000034 method Methods 0.000 title claims description 19
230000008569 process Effects 0.000 title claims description 13
238000004519 manufacturing process Methods 0.000 title claims description 10
239000000203 mixture Substances 0.000 title description 26
239000000126 substance Substances 0.000 title description 19
150000002475 indoles Chemical class 0.000 title description 2
239000013067 intermediate product Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 96
125000000217 alkyl group Chemical group 0.000 claims abstract description 32
125000003545 alkoxy group Chemical group 0.000 claims abstract description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
125000002252 acyl group Chemical group 0.000 claims abstract description 10
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 62
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 23
-1 carboxy, hydroxy Chemical group 0.000 claims description 22
239000000460 chlorine Substances 0.000 claims description 21
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
229910052801 chlorine Inorganic materials 0.000 claims description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
229910052794 bromium Inorganic materials 0.000 claims description 11
HBBKFNCURJQICW-UHFFFAOYSA-N pyrimido[1,2-a]indole Chemical compound C1=CC=NC2=CC3=CC=CC=C3N21 HBBKFNCURJQICW-UHFFFAOYSA-N 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
229910052731 fluorine Inorganic materials 0.000 claims description 8
239000011737 fluorine Substances 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
150000001735 carboxylic acids Chemical class 0.000 claims description 7
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
239000012442 inert solvent Substances 0.000 claims description 6
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 4
125000004093 cyano group Chemical group *C#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
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical class OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 claims description 2
238000007796 conventional method Methods 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
UKMKILQLHSRSQM-UHFFFAOYSA-N nitro carbonofluoridate Chemical compound [O-][N+](=O)OC(F)=O UKMKILQLHSRSQM-UHFFFAOYSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
125000001475 halogen functional group Chemical group 0.000 abstract 2
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
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 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 25
238000001228 spectrum Methods 0.000 description 25
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000007858 starting material Substances 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
239000003208 petroleum Substances 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
150000003626 triacylglycerols Chemical class 0.000 description 18
238000005160 1H NMR spectroscopy Methods 0.000 description 17
210000002966 serum Anatomy 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
239000002904 solvent Substances 0.000 description 16
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
239000000725 suspension Substances 0.000 description 15
239000002253 acid Substances 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
239000002585 base Substances 0.000 description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
241001465754 Metazoa Species 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 12
108010062497 VLDL Lipoproteins Proteins 0.000 description 11
239000002245 particle Substances 0.000 description 11
239000002244 precipitate Substances 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
150000007513 acids Chemical class 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
235000019441 ethanol Nutrition 0.000 description 10
238000012360 testing method Methods 0.000 description 10
102000006991 Apolipoprotein B-100 Human genes 0.000 description 9
108010008150 Apolipoprotein B-100 Proteins 0.000 description 9
241000416162 Astragalus gummifer Species 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
229920001615 Tragacanth Polymers 0.000 description 9
238000001816 cooling Methods 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
238000007127 saponification reaction Methods 0.000 description 9
239000000196 tragacanth Substances 0.000 description 9
235000010487 tragacanth Nutrition 0.000 description 9
229940116362 tragacanth Drugs 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
239000011734 sodium Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
241000700159 Rattus Species 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
239000000047 product Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
238000003756 stirring Methods 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-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
230000000694 effects Effects 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000000463 material Substances 0.000 description 6
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
229910000027 potassium carbonate Inorganic materials 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
102000004895 Lipoproteins Human genes 0.000 description 5
108090001030 Lipoproteins Proteins 0.000 description 5
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
229910000069 nitrogen hydride Inorganic materials 0.000 description 5
239000004006 olive oil Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
230000028327 secretion Effects 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
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
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 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
235000011054 acetic acid Nutrition 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
230000037396 body weight Effects 0.000 description 4
238000009835 boiling Methods 0.000 description 4
235000012000 cholesterol Nutrition 0.000 description 4
208000029078 coronary artery disease Diseases 0.000 description 4
239000012043 crude product Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000003599 detergent Substances 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
229940079593 drug Drugs 0.000 description 4
230000026030 halogenation Effects 0.000 description 4
238000005658 halogenation reaction Methods 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
235000008390 olive oil Nutrition 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000004033 plastic Substances 0.000 description 4
230000000291 postprandial effect Effects 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
235000017550 sodium carbonate Nutrition 0.000 description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
210000003462 vein Anatomy 0.000 description 4
OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 description 3
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238000007911 parenteral administration Methods 0.000 description 1
238000003359 percent control normalization Methods 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
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239000006187 pill Substances 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
MKNZKCSKEUHUPM-UHFFFAOYSA-N potassium;butan-1-ol Chemical compound [K+].CCCCO MKNZKCSKEUHUPM-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000012256 powdered iron Substances 0.000 description 1
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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
108090000623 proteins and genes Proteins 0.000 description 1
ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 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
230000011514 reflex Effects 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
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239000011975 tartaric acid Substances 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
JNXWYJWBRZOTAF-UHFFFAOYSA-N tert-butyl 2-(4-methylphenyl)acetate Chemical compound CC1=CC=C(CC(=O)OC(C)(C)C)C=C1 JNXWYJWBRZOTAF-UHFFFAOYSA-N 0.000 description 1
BHAROVLESINHSM-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1.CC1=CC=CC=C1 BHAROVLESINHSM-UHFFFAOYSA-N 0.000 description 1
238000013519 translation Methods 0.000 description 1
229960002415 trichloroethylene Drugs 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
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
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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

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK427-97A 1996-04-04 1997-04-03 Pyrido£1,2-a|indoles, process for their production, pharmauceutical compositions containing said substances, intermediate products for their production and their use SK42797A3 (en)

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 (1)

Publication Number	Publication Date
SK42797A3 true SK42797A3 (en)	1997-11-05

Family

ID=7790502

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK427-97A SK42797A3 (en)	1996-04-04	1997-04-03	Pyrido£1,2-a\|indoles, process for their production, pharmauceutical compositions containing said substances, intermediate products for their production and their use

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)

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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
NZ549721A (en)	2004-03-05	2010-08-27	Univ Pennsylvania	Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side-effects
US20080280922A1 (en) *	2004-04-09	2008-11-13	Marc Alois Celine Maria Engelen	Intermittent Dosing Regimen For Overweight and Obese Subjects
WO2006124405A2 (fr)	2005-05-12	2006-11-23	C.R. Bard Inc.	Filtre amovible pour caillot sanguin ou embole
JP2008542255A (ja) *	2005-05-27	2008-11-27	ファイザー・プロダクツ・インク	肥満症の治療または体重減量の維持のためのカンナビノイド−１受容体アンタゴニストおよびミクロソームトリグリセリド輸送タンパク質阻害物質の併用
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
JP2009511635A (ja) *	2005-10-18	2009-03-19	エージェリオンファーマシューティカルズ	哺乳動物における高脂血症に関連する障害を治療するための方法
US10188496B2 (en)	2006-05-02	2019-01-29	C. R. Bard, Inc.	Vena cava filter formed from a sheet
US20080161279A1 (en) *	2006-12-21	2008-07-03	Wisler Gerald L	Methods of Treating Obesity
EP4188372A1 (fr)	2020-07-29	2023-06-07	Amryt Pharmaceuticals Inc.	Lomitapide destiné à être utilisé dans des méthodes de traitement de l'hyperlipidémie et de l'hypercholestérolémie chez des patients pédiatriques

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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
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
US5576342A (en) *	1992-03-13	1996-11-19	Bayer Aktiengesellschaft	Phenylglycinamides of heterocyclically substitued phenylacetic acid derivatives
DE4208052A1 (de) *	1992-03-13	1993-09-16	Bayer Ag	Imidazolyl substituierte phenylessigsaeureamide
US5705498A (en) *	1992-11-05	1998-01-06	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 CA CA002201434A patent/CA2201434A1/fr not_active Abandoned
- 1997-04-01 SG SG1997001026A patent/SG63698A1/en unknown
- 1997-04-01 YU YU12397A patent/YU12397A/sr unknown
- 1997-04-01 MA MA24544A patent/MA24131A1/fr unknown
- 1997-04-02 TR TR97/00261A patent/TR199700261A2/xx unknown
- 1997-04-02 BG BG101379A patent/BG62934B1/bg unknown
- 1997-04-02 TN TNTNSN97061A patent/TNSN97061A1/fr 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 DZ DZ970048A patent/DZ2201A1/fr active
- 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 JP JP9097893A patent/JPH1059972A/ja not_active Withdrawn
- 1997-04-03 AR ARP970101336A patent/AR006497A1/es unknown
- 1997-04-03 KR KR1019970012342A patent/KR970070008A/ko not_active Withdrawn
- 1997-04-03 ZA ZA9702829A patent/ZA972829B/xx unknown
- 1997-04-03 SK SK427-97A patent/SK42797A3/sk unknown
- 1997-04-03 MY MYPI97001435A patent/MY126362A/en unknown
- 1997-04-03 NO NO971512A patent/NO309092B1/no not_active IP Right Cessation
- 1997-04-03 CO CO97016906A patent/CO4520306A1/es unknown
- 1997-04-03 EE EE9700078A patent/EE9700078A/xx unknown
- 1997-04-03 PE PE1997000260A patent/PE42398A1/es not_active Application Discontinuation
- 1997-04-03 CZ CZ971022A patent/CZ102297A3/cs unknown
- 1997-04-04 SV SV1997000025A patent/SV1997000025A/es unknown
- 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
1999
- 1999-08-30 IL IL13164599A patent/IL131645A0/xx unknown
2000
- 2000-09-12 CN CN00127092A patent/CN1312246A/zh active Pending

Also Published As

Publication number	Publication date
EP0799828A2 (fr)	1997-10-08
YU12397A (en)	1999-11-22
CZ102297A3 (en)	1997-10-15
HRP970154A2 (en)	1998-04-30
SG63698A1 (en)	1999-03-30
IL131645A0 (en)	2001-01-28
MX9702445A (es)	1997-10-31
PE42398A1 (es)	1998-10-12
NZ314497A (en)	1999-10-28
MA24131A1 (fr)	1997-10-01
TR199700261A2 (xx)	1997-10-21
ZA972829B (en)	1997-10-31
ID16520A (id)	1997-10-09
EP0799828A3 (fr)	1998-04-08
HUP9700708A3 (en)	2000-01-28
TNSN97061A1 (fr)	2005-03-15
AU1660397A (en)	1997-10-09
CN1312246A (zh)	2001-09-12
DE19613550A1 (de)	1997-10-09
IL120590A (en)	2000-02-17
HU9700708D0 (en)	1997-05-28
AU725786B2 (en)	2000-10-19
CO4520306A1 (es)	1997-10-15
JPH1059972A (ja)	1998-03-03
SV1997000025A (es)	1997-10-23
NO971512D0 (no)	1997-04-03
HN1997000045A (es)	1997-06-26
MY126362A (en)	2006-09-29
AR006497A1 (es)	1999-08-25
NO309092B1 (no)	2000-12-11
EE9700078A (et)	1997-10-15
IL120590A0 (en)	1997-08-14
IL131645A (en)	2000-12-06
HUP9700708A2 (hu)	1998-10-28
PL319249A1 (en)	1997-10-13
BR9701675A (pt)	1998-11-03
US6114341A (en)	2000-09-05
KR970070008A (ko)	1997-11-07
BG101379A (en)	1997-11-28
CN1176965A (zh)	1998-03-25
BG62934B1 (bg)	2000-11-30
NO971512L (no)	1997-10-06
DZ2201A1 (fr)	2002-12-03
CN1067393C (zh)	2001-06-20
CA2201434A1 (fr)	1997-10-04

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US6245775B1 (en)	2001-06-12	Cycloalkano-indole and -azaindole derivatives
US5356911A (en)	1994-10-18	Substituted biphenylpyridones
US6114341A (en)	2000-09-05	Pyrimido[1,2-a]indoles
HUT55367A (en)	1991-05-28	Process for producing biphenylmethane derivatives including condensed carbo or heterocyclic imidazole unit, as well as pharmaceutical compositions comprising such compounds
EP0481429A2 (fr)	1992-04-22	Dérivés de quinoléine
PL160188B1 (pl)	1993-02-26	Sposób wytwarzania nowych pochodnych tetraliny lub chromanu PL PL PL PL PL PL PL
JPH09183766A (ja)	1997-07-15	二環式複素環式化合物
US6194424B1 (en)	2001-02-27	Arylacetamides and their use as medicaments
US5786361A (en)	1998-07-28	Pyridazino-, pyrimido-, pyrazino- and triazinoindoles, -pyrrolocycloalkenes or pyrrolooxocycloalkenes, or pyridopyrrolylpyrido compounds, compositions containing them, and use thereof to treat atherosclerosis
US5830902A (en)	1998-11-03	Quinuclidine derivative having tricyclic hetero condensed ring
MXPA97002445A (en)	1998-07-03	New pyrimid [1,2-] indo
HK1003384A (en)	1998-10-30	Novel pyrimido[1,2-a]indole
JPH0948777A (ja)	1997-02-18	ジアゼピノン類、その製造法および剤
HK1011351B (en)	2001-09-28	Quinoline derivatives