BG62934B1 - НОВИ ПИРИМИДО(1,2-а)ИНДОЛИ - Google Patents

НОВИ ПИРИМИДО(1,2-а)ИНДОЛИ Download PDF

Info

Publication number: BG62934B1
Authority: BG; Bulgaria
Prior art keywords: carbon atoms; branched; branched chain; alkyl; optionally substituted
Prior art date: 1996-04-04

Application number

BG101379A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG101379A (en

Inventor

Ulrich Mueller

Peter Eckenberg

Rudi Gruetzmann

Hilmar Bischoff

Dirk Denzer

Stefan Wohlfeil

Stefan Lohmer

Ulrich Nielsch

Peter Kolkhof

Original Assignee

Bayer Aktiengesellschaft

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

1997-04-02

Publication date

2000-11-30

1997-04-02 Application filed by Bayer Aktiengesellschaft filed Critical Bayer Aktiengesellschaft

1997-11-28 Publication of BG101379A publication Critical patent/BG101379A/xx

2000-11-30 Publication of BG62934B1 publication Critical patent/BG62934B1/bg

Links

150000002475 indoles Chemical class 0.000 title description 2
238000006243 chemical reaction Methods 0.000 claims abstract description 28
238000002360 preparation method Methods 0.000 claims abstract description 14
HBBKFNCURJQICW-UHFFFAOYSA-N pyrimido[1,2-a]indole Chemical class C1=CC=NC2=CC3=CC=CC=C3N21 HBBKFNCURJQICW-UHFFFAOYSA-N 0.000 claims abstract description 10
IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical class OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 111
125000004432 carbon atom Chemical group C* 0.000 claims description 68
238000000034 method Methods 0.000 claims description 42
-1 carboxy, hydroxy Chemical group 0.000 claims description 38
125000000217 alkyl group Chemical group 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 26
239000000460 chlorine Substances 0.000 claims description 24
229910052801 chlorine Inorganic materials 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
229910052794 bromium Inorganic materials 0.000 claims description 15
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
150000002148 esters Chemical class 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
150000001735 carboxylic acids Chemical class 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 8
125000003342 alkenyl 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
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
239000012442 inert solvent Substances 0.000 claims description 8
239000002552 dosage form Substances 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
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 5
201000001320 Atherosclerosis Diseases 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
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
125000004429 atom Chemical group 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 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
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
150000002221 fluorine Chemical class 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
239000004480 active ingredient Substances 0.000 abstract description 6
230000000694 effects Effects 0.000 abstract description 6
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 abstract 2
229960003424 phenylacetic acid Drugs 0.000 abstract 1
239000003279 phenylacetic acid Substances 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 37
239000000243 solution Substances 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
229940093499 ethyl acetate Drugs 0.000 description 23
238000001228 spectrum Methods 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
239000003208 petroleum Substances 0.000 description 20
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 19
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 18
239000002904 solvent Substances 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
239000002253 acid Substances 0.000 description 16
238000005160 1H NMR spectroscopy Methods 0.000 description 15
210000002966 serum Anatomy 0.000 description 15
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 15
241001465754 Metazoa Species 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
239000000725 suspension Substances 0.000 description 14
239000002244 precipitate Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
108010007622 LDL Lipoproteins Proteins 0.000 description 11
102000007330 LDL Lipoproteins Human genes 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
102000018616 Apolipoproteins B Human genes 0.000 description 10
108010027006 Apolipoproteins B Proteins 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
238000012360 testing method Methods 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
150000003626 triacylglycerols Chemical class 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
238000001914 filtration Methods 0.000 description 9
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
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 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
229960001701 chloroform Drugs 0.000 description 8
238000001816 cooling Methods 0.000 description 8
239000002245 particle Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000007127 saponification reaction Methods 0.000 description 8
239000011734 sodium Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-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
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
239000012043 crude product Substances 0.000 description 7
238000001819 mass spectrum Methods 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-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
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
229950005499 carbon tetrachloride Drugs 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000004006 olive oil Substances 0.000 description 6
235000008390 olive oil Nutrition 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
239000011780 sodium chloride Substances 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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
102000004895 Lipoproteins Human genes 0.000 description 5
108090001030 Lipoproteins Proteins 0.000 description 5
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 5
239000003814 drug Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000011574 phosphorus Substances 0.000 description 5
229910052698 phosphorus Inorganic materials 0.000 description 5
230000028327 secretion Effects 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
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 4
229960000583 acetic acid Drugs 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000037396 body weight Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
235000012000 cholesterol Nutrition 0.000 description 4
208000029078 coronary artery disease Diseases 0.000 description 4
239000013078 crystal Substances 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
150000004679 hydroxides Chemical class 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 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
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
238000003556 assay Methods 0.000 description 3
210000004204 blood vessel Anatomy 0.000 description 3
238000009835 boiling Methods 0.000 description 3
150000004649 carbonic acid derivatives Chemical class 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
210000005229 liver cell Anatomy 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
238000012545 processing Methods 0.000 description 3
238000000746 purification Methods 0.000 description 3
235000017550 sodium carbonate Nutrition 0.000 description 3
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125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
238000010241 blood sampling Methods 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
229950001261 camiglibose Drugs 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
230000035602 clotting Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
229960002887 deanol Drugs 0.000 description 1
239000007857 degradation product Substances 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
239000012973 diazabicyclooctane Substances 0.000 description 1
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
KXEKODJGRSIGAU-UHFFFAOYSA-N ethyl 2-amino-1h-indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=C(N)NC2=C1 KXEKODJGRSIGAU-UHFFFAOYSA-N 0.000 description 1
ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
201000005577 familial hyperlipidemia Diseases 0.000 description 1
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
239000003337 fertilizer Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
150000002238 fumaric acids Chemical class 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
208000006575 hypertriglyceridemia Diseases 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
239000003547 immunosorbent Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000031891 intestinal absorption Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000003350 kerosene Substances 0.000 description 1
VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
150000002689 maleic acids Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
AWTKFTNNPQGGLX-UHFFFAOYSA-N methyl 2-(3-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(C)=C1 AWTKFTNNPQGGLX-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000004089 microcirculation Effects 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
MFXMNSMTYUGIGR-UHFFFAOYSA-N n-[acetyl(methyl)amino]-n-phenylnitrous amide Chemical compound CC(=O)N(C)N(N=O)C1=CC=CC=C1 MFXMNSMTYUGIGR-UHFFFAOYSA-N 0.000 description 1
229940105631 nembutal Drugs 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
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
230000020477 pH reduction Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
150000005331 phenylglycines Chemical class 0.000 description 1
PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 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
239000002243 precursor Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 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
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000011514 reflex Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
241000894007 species Species 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229950001790 tendamistat Drugs 0.000 description 1
108010037401 tendamistate Proteins 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 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
229940086542 triethylamine 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
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-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
208000021331 vascular occlusion disease Diseases 0.000 description 1
238000012795 verification Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 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)
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)

BG101379A 1996-04-04 1997-04-02 НОВИ ПИРИМИДО(1,2-а)ИНДОЛИ BG62934B1 (bg)

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 (2)

Publication Number	Publication Date
BG101379A BG101379A (en)	1997-11-28
BG62934B1 true BG62934B1 (bg)	2000-11-30

Family

ID=7790502

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG101379A BG62934B1 (bg)	1996-04-04	1997-04-02	НОВИ ПИРИМИДО(1,2-а)ИНДОЛИ

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)	IL131645A (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 (14)

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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
WO2001074817A1 (fr) *	2000-03-30	2001-10-11	Yamanouchi Pharmaceutical Co., Ltd.	Derives d'hydrazide
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
US7932268B2 (en)	2004-03-05	2011-04-26	The Trustees Of The University Of Pennsylvania	Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side effects
AU2005230397B2 (en) *	2004-04-09	2010-04-08	Elanco Animal Health Ireland Limited	Intermittent dosing regimen for the treatment of overweight with MTP-inhibitors
US7967838B2 (en)	2005-05-12	2011-06-28	C. R. Bard, Inc.	Removable embolus blood clot filter
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
CA2616818C (fr)	2005-08-09	2014-08-05	C.R. Bard, Inc.	Filtre pour caillots de sang generateurs d'embolie et systeme de mise en place
EP1951220A2 (fr) *	2005-10-18	2008-08-06	Aegerion Pharmaceuticals	Compositions destinees a l'abbaissement du cholesterol serique et/ou des triglycerides
US10188496B2 (en)	2006-05-02	2019-01-29	C. R. Bard, Inc.	Vena cava filter formed from a sheet
CA2673290A1 (fr) *	2006-12-21	2008-07-03	Aegerion Pharmaceuticals, Inc.	Procedes de traitement de l'obesite a l'aide d'une combinaison comprenant un inhibiteur de mtp et un inhibiteur de l'absorption du cholesterol
US20230285376A1 (en)	2020-07-29	2023-09-14	Amryt Pharmaceuticals Inc.	Lomitapide for use in methods of treating hyperlipidemia and hypercholesterolemia in pediatric patients

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2200584A1 (de) *	1971-01-11	1972-07-27	Wyeth John & Brother Ltd	Heterocyclische Verbindungen,Verfahren zu ihrer Herstellung und ihre Verwendung in pharmazeutischen Zubereitungen
ZA718536B (en) *	1971-01-11	1972-09-27	Wyeth John & Brother Ltd	Heterocyclic compounds
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
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
DE4309968A1 (de) *	1993-03-26	1994-09-29	Bayer Ag	Phenylglycinamide von heterocyclisch substituierten Phenylessigsäurederivaten
NZ257545A (en) *	1992-11-05	1997-01-29	Smithkline Beecham Plc	Heterocyclic (especially piperidine) derivatives and pharmaceutical compositions
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 SG SG1997001026A patent/SG63698A1/en unknown
- 1997-04-01 MA MA24544A patent/MA24131A1/fr unknown
- 1997-04-01 CA CA002201434A patent/CA2201434A1/fr not_active Abandoned
- 1997-04-02 IL IL13164597A patent/IL131645A/xx not_active IP Right Cessation
- 1997-04-02 TR TR97/00261A patent/TR199700261A2/xx 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 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 ID IDP971112A patent/ID16520A/id unknown
- 1997-04-03 CZ CZ971022A patent/CZ102297A3/cs unknown
- 1997-04-03 CO CO97016906A patent/CO4520306A1/es unknown
- 1997-04-03 KR KR1019970012342A patent/KR970070008A/ko not_active Withdrawn
- 1997-04-03 MY MYPI97001435A patent/MY126362A/en unknown
- 1997-04-03 AR ARP970101336A patent/AR006497A1/es unknown
- 1997-04-03 EE EE9700078A patent/EE9700078A/xx unknown
- 1997-04-03 NO NO971512A patent/NO309092B1/no not_active IP Right Cessation
- 1997-04-03 PE PE1997000260A patent/PE42398A1/es not_active Application Discontinuation
- 1997-04-03 SK SK427-97A patent/SK42797A3/sk unknown
- 1997-04-03 ZA ZA9702829A patent/ZA972829B/xx unknown
- 1997-04-04 CN CN97110275A patent/CN1067393C/zh not_active Expired - Fee Related
- 1997-04-04 HU HU9700708A patent/HUP9700708A3/hu unknown
- 1997-04-04 BR BR9701675A patent/BR9701675A/pt active Search and Examination
- 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

Also Published As

Publication number	Publication date
SV1997000025A (es)	1997-10-23
ZA972829B (en)	1997-10-31
IL131645A0 (en)	2001-01-28
SG63698A1 (en)	1999-03-30
CO4520306A1 (es)	1997-10-15
MX9702445A (es)	1997-10-31
NO971512L (no)	1997-10-06
NO309092B1 (no)	2000-12-11
NO971512D0 (no)	1997-04-03
HUP9700708A3 (en)	2000-01-28
DE19613550A1 (de)	1997-10-09
AR006497A1 (es)	1999-08-25
ID16520A (id)	1997-10-09
MA24131A1 (fr)	1997-10-01
MY126362A (en)	2006-09-29
HRP970154A2 (en)	1998-04-30
HU9700708D0 (en)	1997-05-28
BG101379A (en)	1997-11-28
NZ314497A (en)	1999-10-28
IL131645A (en)	2000-12-06
CN1176965A (zh)	1998-03-25
BR9701675A (pt)	1998-11-03
CN1312246A (zh)	2001-09-12
KR970070008A (ko)	1997-11-07
HUP9700708A2 (hu)	1998-10-28
EP0799828A2 (fr)	1997-10-08
IL120590A0 (en)	1997-08-14
CZ102297A3 (en)	1997-10-15
AU1660397A (en)	1997-10-09
DZ2201A1 (fr)	2002-12-03
JPH1059972A (ja)	1998-03-03
SK42797A3 (en)	1997-11-05
EE9700078A (et)	1997-10-15
TR199700261A2 (xx)	1997-10-21
CA2201434A1 (fr)	1997-10-04
AU725786B2 (en)	2000-10-19
CN1067393C (zh)	2001-06-20
EP0799828A3 (fr)	1998-04-08
IL120590A (en)	2000-02-17
PE42398A1 (es)	1998-10-12
PL319249A1 (en)	1997-10-13
TNSN97061A1 (fr)	2005-03-15
YU12397A (en)	1999-11-22
US6114341A (en)	2000-09-05
HN1997000045A (es)	1997-06-26

Publication	Publication Date	Title
US6245775B1 (en)	2001-06-12	Cycloalkano-indole and -azaindole derivatives
US5356911A (en)	1994-10-18	Substituted biphenylpyridones
BG62934B1 (bg)	2000-11-30	НОВИ ПИРИМИДО(1,2-а)ИНДОЛИ
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
CA2186086A1 (fr)	1997-03-26	Derives de substitution de xanthines
CA2202703A1 (fr)	1997-10-18	Nouveaux pyridazino-, pyrimido-, pyrazino- et triazino-indoles
US6034115A (en)	2000-03-07	Indolyl-substituted phenylacetic acid derivatives
US6194424B1 (en)	2001-02-27	Arylacetamides and their use as medicaments
US6255330B1 (en)	2001-07-03	Heterocyclically substituted phenylglycinolamides
MXPA97002445A (en)	1998-07-03	New pyrimid [1,2-] indo
HK1003384A (en)	1998-10-30	Novel pyrimido[1,2-a]indole