NO321985B1 - Dihydropyrimidinforbindelser, fremgangsmater for fremstilling av slike, samt fremgangsmate for fremstilling av farmasoytiske preparater og anvendelse av forbindelsene i farmasoytiske preparater for behandling av virussykdommer, saerlig hepatitt B - Google Patents

Dihydropyrimidinforbindelser, fremgangsmater for fremstilling av slike, samt fremgangsmate for fremstilling av farmasoytiske preparater og anvendelse av forbindelsene i farmasoytiske preparater for behandling av virussykdommer, saerlig hepatitt B Download PDF

Info

Publication number: NO321985B1
Authority: NO; Norway
Prior art keywords: general formula; compounds; alkyl; amino; differently
Prior art date: 1998-04-18

Application number

NO20005215A

Other languages

English (en)

Norwegian (no)

Other versions

NO20005215D0 (no

NO20005215L (no

Inventor

Arnold Paessens

Juergen Stoltefuss

Siegfried Goldmann

Thomas Kramer

Ulrich Niewohner

Karl-Heinz Schlemmer

Olaf Weber

Erwin Graef

Stefan Lottmann

Kark Deres

Jorn Stolting

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.)

1998-04-18

Filing date

2000-10-17

Publication date

2006-07-31

2000-10-17 Application filed by Bayer Ag filed Critical Bayer Ag

2000-10-17 Publication of NO20005215D0 publication Critical patent/NO20005215D0/no

2000-12-13 Publication of NO20005215L publication Critical patent/NO20005215L/no

2006-07-31 Publication of NO321985B1 publication Critical patent/NO321985B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 54
238000000034 method Methods 0.000 title claims description 22
238000011282 treatment Methods 0.000 title claims description 10
239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
201000010099 disease Diseases 0.000 title claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 7
230000003612 virological effect Effects 0.000 title claims description 4
208000002672 hepatitis B Diseases 0.000 title description 7
WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical class C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 title description 2
-1 trifluoromethoxy, carboxyl Chemical group 0.000 claims description 22
150000003839 salts Chemical class 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 14
125000004432 carbon atom Chemical group C* 0.000 claims description 13
239000000460 chlorine Substances 0.000 claims description 13
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
239000011737 fluorine Substances 0.000 claims description 9
229910052731 fluorine Inorganic materials 0.000 claims description 9
125000004076 pyridyl group Chemical group 0.000 claims description 9
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
239000004480 active ingredient Substances 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
150000001409 amidines Chemical class 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
230000001154 acute effect Effects 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 5
230000001684 chronic effect Effects 0.000 claims description 5
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
150000003863 ammonium salts Chemical class 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
208000016350 chronic hepatitis B virus infection Diseases 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
150000002463 imidates Chemical class 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
229920006395 saturated elastomer Polymers 0.000 claims description 3
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
206010059193 Acute hepatitis B Diseases 0.000 claims description 2
208000037628 acute hepatitis B virus infection Diseases 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
150000003840 hydrochlorides Chemical class 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
229940126601 medicinal product Drugs 0.000 claims 3
125000001183 hydrocarbyl group Chemical group 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
210000004027 cell Anatomy 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
239000006228 supernatant Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
108020004414 DNA Proteins 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
SOGUCWFOKBJAQO-UHFFFAOYSA-N methyl 2-[(2-chloro-4-fluorophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)=CC1=CC=C(F)C=C1Cl SOGUCWFOKBJAQO-UHFFFAOYSA-N 0.000 description 6
ATUOLSDAAPMVJJ-UHFFFAOYSA-N 3,5-dichloropyridine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C(Cl)=C1 ATUOLSDAAPMVJJ-UHFFFAOYSA-N 0.000 description 5
WDLIDNANRSUVFL-UHFFFAOYSA-N 3,5-difluoropyridine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NC=C(F)C=C1F WDLIDNANRSUVFL-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
150000001299 aldehydes Chemical group 0.000 description 5
230000000840 anti-viral effect Effects 0.000 description 5
235000019439 ethyl acetate Nutrition 0.000 description 5
239000001963 growth medium Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000002585 base Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000001514 detection method Methods 0.000 description 4
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
238000009396 hybridization Methods 0.000 description 4
239000000203 mixture Substances 0.000 description 4
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
239000000047 product Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 4
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
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
239000004677 Nylon Substances 0.000 description 3
208000036142 Viral infection Diseases 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
231100000433 cytotoxic Toxicity 0.000 description 3
230000001472 cytotoxic effect Effects 0.000 description 3
239000012528 membrane Substances 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229920001778 nylon Polymers 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
230000009385 viral infection Effects 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 2
102000002260 Alkaline Phosphatase Human genes 0.000 description 2
108020004774 Alkaline Phosphatase Proteins 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
241000700721 Hepatitis B virus Species 0.000 description 2
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 2
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
108020005202 Viral DNA Proteins 0.000 description 2
241000700605 Viruses Species 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003921 oil Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000011698 potassium fluoride Substances 0.000 description 2
235000003270 potassium fluoride Nutrition 0.000 description 2
238000000926 separation method Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000010186 staining Methods 0.000 description 2
BRKFQVAOMSWFDU-UHFFFAOYSA-M tetraphenylphosphanium;bromide Chemical compound [Br-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BRKFQVAOMSWFDU-UHFFFAOYSA-M 0.000 description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
CNLIIAKAAMFCJG-UHFFFAOYSA-N 2,3,5-trichloropyridine Chemical compound ClC1=CN=C(Cl)C(Cl)=C1 CNLIIAKAAMFCJG-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
KMQWNQKESAHDKD-UHFFFAOYSA-N 2-chloro-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Cl)=C1 KMQWNQKESAHDKD-UHFFFAOYSA-N 0.000 description 1
RODXBOIDZPQDBH-UHFFFAOYSA-N 3,5-dichloro-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC(Cl)=CC(Cl)=C1 RODXBOIDZPQDBH-UHFFFAOYSA-N 0.000 description 1
DUKJVWUITYUNPT-UHFFFAOYSA-N 3,5-difluoropyridine-2-carboximidamide Chemical compound NC(=N)C1=NC=C(F)C=C1F DUKJVWUITYUNPT-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
QVGBDRDOWKIYHK-UHFFFAOYSA-N 3-fluoro-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=CC(F)=C1 QVGBDRDOWKIYHK-UHFFFAOYSA-N 0.000 description 1
CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 1
VZFPSCNTFBJZHB-UHFFFAOYSA-N 3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC=CN=C1C#N VZFPSCNTFBJZHB-UHFFFAOYSA-N 0.000 description 1
BDCLDNALSPBWPQ-UHFFFAOYSA-N 3-oxohexanoic acid Chemical compound CCCC(=O)CC(O)=O BDCLDNALSPBWPQ-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
208000000419 Chronic Hepatitis B Diseases 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
239000003298 DNA probe Substances 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
208000037319 Hepatitis infectious Diseases 0.000 description 1
238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
QWXOJIDBSHLIFI-UHFFFAOYSA-N [3-(1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl)phenyl] dihydrogen phosphate Chemical compound O1OC2(C3CC4CC2CC(Cl)(C4)C3)C1(OC)C1=CC=CC(OP(O)(O)=O)=C1 QWXOJIDBSHLIFI-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
244000309464 bull Species 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
159000000007 calcium salts Chemical class 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
239000000824 cytostatic agent Substances 0.000 description 1
230000001085 cytostatic effect Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
229960002887 deanol Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
229960005156 digoxin Drugs 0.000 description 1
LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003480 eluent Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
IMBKASBLAKCLEM-UHFFFAOYSA-L ferrous ammonium sulfate (anhydrous) Chemical compound [NH4+].[NH4+].[Fe+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O IMBKASBLAKCLEM-UHFFFAOYSA-L 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
208000005252 hepatitis A Diseases 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
229940094991 herring sperm dna Drugs 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
150000002431 hydrogen Chemical class 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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
125000001624 naphthyl group Chemical group 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
210000004976 peripheral blood cell Anatomy 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
229920000151 polyglycol Polymers 0.000 description 1
239000010695 polyglycol Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000000523 sample Substances 0.000 description 1
108700004121 sarkosyl Proteins 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000002477 vacuolizing effect Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
210000002845 virion Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Bioinformatics & Cheminformatics (AREA)
Virology (AREA)
Gastroenterology & Hepatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Saccharide Compounds (AREA)

NO20005215A 1998-04-18 2000-10-17 Dihydropyrimidinforbindelser, fremgangsmater for fremstilling av slike, samt fremgangsmate for fremstilling av farmasoytiske preparater og anvendelse av forbindelsene i farmasoytiske preparater for behandling av virussykdommer, saerlig hepatitt B NO321985B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19817264A DE19817264A1 (de)	1998-04-18	1998-04-18	Neue Dihydropyrimidine
PCT/EP1999/002344 WO1999054326A1 (de)	1998-04-18	1999-04-07	Dihydropyrimidine

Publications (3)

Publication Number	Publication Date
NO20005215D0 NO20005215D0 (no)	2000-10-17
NO20005215L NO20005215L (no)	2000-12-13
NO321985B1 true NO321985B1 (no)	2006-07-31

Family

ID=7864972

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20005215A NO321985B1 (no)	1998-04-18	2000-10-17	Dihydropyrimidinforbindelser, fremgangsmater for fremstilling av slike, samt fremgangsmate for fremstilling av farmasoytiske preparater og anvendelse av forbindelsene i farmasoytiske preparater for behandling av virussykdommer, saerlig hepatitt B
NO20045259A NO329020B1 (no)	1998-04-18	2004-12-01	Difluorpyridiner

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20045259A NO329020B1 (no)	1998-04-18	2004-12-01	Difluorpyridiner

Country Status (36)

Country	Link
US (3)	US6696451B1 (2)
EP (1)	EP1080086B1 (2)
JP (2)	JP4590097B2 (2)
KR (1)	KR100636771B1 (2)
CN (1)	CN1159311C (2)
AR (1)	AR018187A1 (2)
AT (1)	ATE223401T1 (2)
AU (1)	AU740318B2 (2)
BG (1)	BG64649B1 (2)
BR (2)	BRPI9917862B8 (2)
CA (1)	CA2328780C (2)
CO (1)	CO5021127A1 (2)
CU (1)	CU23049A3 (2)
CZ (1)	CZ293482B6 (2)
DE (2)	DE19817264A1 (2)
DK (1)	DK1080086T3 (2)
ES (1)	ES2183548T3 (2)
GT (1)	GT199900056A (2)
HU (1)	HUP0102372A3 (2)
ID (1)	ID27263A (2)
IL (2)	IL138584A0 (2)
MY (1)	MY126527A (2)
NO (2)	NO321985B1 (2)
NZ (1)	NZ507569A (2)
PE (1)	PE20000427A1 (2)
PL (1)	PL193898B1 (2)
PT (1)	PT1080086E (2)
RU (1)	RU2245881C9 (2)
SI (1)	SI1080086T1 (2)
SK (1)	SK286407B6 (2)
SV (1)	SV1999000047A (2)
TR (1)	TR200003011T2 (2)
TW (1)	TW548274B (2)
UA (1)	UA63998C2 (2)
WO (1)	WO1999054326A1 (2)
ZA (1)	ZA200005136B (2)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU4289100A (en) *	1999-03-25	2000-10-16	Bayer Aktiengesellschaft	Dihydropyrimidines and their use in the treatment of hepatitis
EP1193259A4 (en)	1999-06-23	2003-01-29	Ajinomoto Kk	dihydropyrimidine
WO2001045712A1 (de) *	1999-12-22	2001-06-28	Bayer Aktiengesellschaft	Arzneimittelkombinationen gegen virale erkrankungen
DE10012823A1 (de)	2000-03-16	2001-09-20	Bayer Ag	Arzneimittel gegen virale Erkrankungen
DE10013126A1 (de) *	2000-03-17	2001-09-20	Bayer Ag	Arzneimittel gegen virale Erkrankungen
DE10013125A1 (de) *	2000-03-17	2001-09-20	Bayer Ag	Arzneimittel gegen virale Erkrankungen
DE10125131A1 (de) *	2001-05-23	2002-12-05	Bayer Ag	Verfahren zur Spaltung des Methyl 4-(2-chlor-4-fluorphenyl)-2-(3,5-difluor-2-pyridinyl)-6-methyl-1,4-dihydro-5-pyrmidincarboxylat-Racemats
US20040092735A1 (en) *	2002-11-08	2004-05-13	Orchid Chemicals & Pharmaceuticals Limited	Process for the preparation of cefuroxime sodium
CN101104617B (zh) *	2006-07-10	2010-06-23	北京摩力克科技有限公司	二氢嘧啶类化合物及其用于制备治疗和预防病毒性疾病的药物的用途
CN101104604B (zh)	2006-07-10	2011-03-02	北京摩力克科技有限公司	光学纯二氢嘧啶类化合物及其用于制备治疗和预防病毒性疾病的药物的用途
RU2452733C2 (ru) *	2007-04-27	2012-06-10	Пэдью Фарма Л.П.	Антагонисты trpv1 и их применение
CA2691056C (en)	2007-06-18	2014-03-11	Zhang, Zhongneng	Bromo-phenyl substituted thiazolyl dihydropyrimidines for treating and preventing hepatitis b infections
MY147366A (en)	2007-07-12	2012-11-30	Novartis Ag	Oral pharmaceutical solutions containing telbivudine
US20130267517A1 (en)	2012-03-31	2013-10-10	Hoffmann-La Roche Inc.	Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection
AU2013305390C1 (en) *	2012-08-24	2015-12-24	Ruyuan Wei Xiang Technology Co., Ltd.	Dihydropyrimidine compounds and their application in pharmaceuticals
AU2013311705A1 (en)	2012-09-10	2015-02-05	F. Hoffmann-La Roche Ag	6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of Hepatitis B virus infection
CN103664899B (zh) *	2012-09-11	2017-06-16	广东东阳光药业有限公司	杂芳基取代的二氢嘧啶类化合物及其在药物中的应用
CA2889892A1 (en) *	2012-11-09	2014-05-15	Indiana University Research And Technology Corporation	Alternative uses for hbv assembly effectors
TW201609652A (zh) *	2013-11-12	2016-03-16	陶氏農業科學公司	用於氟化化合物之過程（三）
AU2014352404B2 (en)	2013-11-19	2018-07-19	Sunshine Lake Pharma Co., Ltd.	Dihydropyrimidine compounds and their application in pharmaceuticals
AU2014356984B2 (en)	2013-11-27	2018-01-04	Sunshine Lake Pharma Co., Ltd.	Processes for preparing dihydropyrimidine derivatives and intermediates thereof
CA2938050A1 (en)	2014-03-28	2015-10-01	North & South Brother Pharmacy Investment Company Limited	Dihydropyrimidine compounds and their application in pharmaceuticals
NZ727601A (en)	2014-05-30	2022-01-28	Qilu Pharmaceutical Co Ltd	Dihydropyrimido fused ring derivative as hbv inhibitor
CN105153164B (zh) *	2014-05-30	2018-10-30	齐鲁制药有限公司	作为hbv抑制剂的二氢嘧啶并环衍生物
AU2016214799A1 (en)	2015-02-07	2017-06-15	Sunshine Lake Pharma Co., Ltd.	Complexes and salts of dihydropyrimidine derivatives and their application in pharmaceuticals
AU2018291688B2 (en) *	2017-06-27	2022-02-03	Janssen Pharmaceutica Nv	Heteroaryldihydropyrimidine derivatives and methods of treating hepatitis B infections
US10759774B2 (en)	2017-09-28	2020-09-01	The Curators Of The University Of Missouri	Inhibitors of hepatitis B virus targeting capsid assembly
BR112020008765A2 (pt)	2017-11-02	2020-10-20	Aicuris Gmbh & Co. Kg	indol-2-carboxamidas pirazolo-piperidina substituídas altamente ativas inovadoras ativas contra o vírus da hepatite b (hbv)
CA3081386A1 (en)	2017-11-02	2019-05-09	Aicuris Gmbh & Co. Kg	Highly active amino-thiazole substituted indole-2-carboxamides active against the hepatitis b virus (hbv)
JP2021523160A (ja) *	2018-05-08	2021-09-02	ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー	ジヒドロピリミジン誘導体及びｈｂｖ感染又はｈｂｖ誘導性疾患の治療におけるその使用
US11053235B2 (en)	2018-08-09	2021-07-06	Janssen Sciences Ireland Unlimited Company	Substituted 1,4-dihydropyrimidines for the treatment of HBV infection or HBV-induced diseases
PY1991608A (es)	2018-11-02	2022-02-10	Aicuris Gmbh & Co Kg	Nueva urea 6,7-dihidro-4h-pirazolo [1,5-a] pirazina activas contra el virus de la hepatitis b (vhb)
AR116947A1 (es)	2018-11-02	2021-06-30	Aicuris Gmbh & Co Kg	Derivados de urea 6,7-dihidro-4h-pirazolo[1,5-a]pirazinas-indol-2-carboxamidas activas contra el virus de la hepatitis b (vhb)
UY38434A (es)	2018-11-02	2020-05-29	Aicuris Gmbh & Co Kg	Nuevas 6,7-dihidro-4h-pirazolo[1,5-a]pirazin indol-2-carboxamidas activas contra el virus de la hepatitis b (hbv)
PY1991606A (es)	2018-11-02	2022-02-10	Aicuris Gmbh & Co Kg	Nueva urea 6,7-dihidro-4h-pirazolo [4,3-c] piridinas activas contra el virus de la hepatitis b (vhb)
CA3118339A1 (en)	2018-11-02	2020-05-07	Aicuris Gmbh & Co. Kg	Novel urea 6,7-dihydro-4h-thiazolo[5,4-c]pyridines active against the hepatitis b virus (hbv)
UY38435A (es)	2018-11-02	2020-05-29	Aicuris Gmbh & Co Kg	Nuevas urea 6,7-dihidro-4h-pirazol[1,5-a] pirazinas activas contra el virus de la hepatitis b (vhb)
KR20210106421A (ko)	2018-12-20	2021-08-30	얀센 파마슈티카 엔.브이.	헤테로아릴디히드로피리미딘 유도체 및 b형 간염 감염의 치료 방법
EP3962912A1 (en)	2019-04-30	2022-03-09	AiCuris GmbH & Co. KG	Novel phenyl and pyridyl ureas active against the hepatitis b virus (hbv)
MX2021013085A (es)	2019-04-30	2021-11-17	Aicuris Gmbh & Co Kg	Nuevas indol-2-carboxamidas activas contra el virus de la hepatitis b (vhb).
PH12021552733A1 (en)	2019-04-30	2023-01-16	Aicuris Gmbh & Co Kg	Novel indolizine-2-carboxamides active against the hepatitis b virus (hbv)
CU20210090A7 (es)	2019-04-30	2022-06-06	Aicuris Gmbh & Co Kg	Compuestos derivados de oxalil piperazinas activos contra el virus de la hepatitis b (vhb)
WO2020255016A1 (en)	2019-06-18	2020-12-24	Janssen Sciences Ireland Unlimited Company	Combination of hepatitis b virus (hbv) vaccines and dihydropyrimidine derivatives as capsid assembly modulators

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL130304C (2) *	1964-02-12
CH550189A (de)	1971-01-08	1974-06-14	Ciba Geigy Ag	Verfahren zur herstellung von neuen dibenzo (b,f) thiepincarbonsaeuren.
CH569043A5 (2)	1973-01-23	1975-11-14	Ciba Geigy Ag
US4371537A (en) *	1981-08-13	1983-02-01	The Dow Chemical Company	Sulfur-substituted phenoxypyridines having antiviral activity
DE3234684A1 (de)	1982-09-18	1984-03-22	Bayer Ag, 5090 Leverkusen	Neue dihydropyrimidine, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln
JPS60185764A (ja) *	1984-03-05	1985-09-21	Wako Pure Chem Ind Ltd	ピリジン誘導体の新規な製造法
US4698340A (en)	1984-07-19	1987-10-06	Fujisawa Pharmaceutical Co., Ltd.	Pyrimidine derivatives, processes for preparation thereof and composition containing the same
US4727073A (en)	1984-10-01	1988-02-23	Fujisawa Pharmaceutical Co., Ltd.	Pyrimidine derivatives and composition of the same
GB8906168D0 (en) *	1989-03-17	1989-05-04	Pfizer Ltd	Therapeutic agents
KR20000053201A (ko) *	1996-11-12	2000-08-25	한스 루돌프 하우스, 헨리테 브룬너, 베아트리체 귄터	제초제로서 유용한 피라졸 유도체
SE9702564D0 (sv)	1997-07-02	1997-07-02	Astra Ab	New compounds

1998
- 1998-04-18 DE DE19817264A patent/DE19817264A1/de not_active Withdrawn
1999
- 1999-04-07 BR BRPI9917862A patent/BRPI9917862B8/pt not_active IP Right Cessation
- 1999-04-07 KR KR1020007011527A patent/KR100636771B1/ko not_active Expired - Lifetime
- 1999-04-07 ID IDW20002111A patent/ID27263A/id unknown
- 1999-04-07 TR TR2000/03011T patent/TR200003011T2/xx unknown
- 1999-04-07 US US09/673,592 patent/US6696451B1/en not_active Expired - Lifetime
- 1999-04-07 WO PCT/EP1999/002344 patent/WO1999054326A1/de not_active Ceased
- 1999-04-07 PL PL99343481A patent/PL193898B1/pl unknown
- 1999-04-07 CZ CZ20003871A patent/CZ293482B6/cs not_active IP Right Cessation
- 1999-04-07 SI SI9930139T patent/SI1080086T1/xx unknown
- 1999-04-07 DK DK99920603T patent/DK1080086T3/da active
- 1999-04-07 NZ NZ507569A patent/NZ507569A/en not_active IP Right Cessation
- 1999-04-07 AU AU38133/99A patent/AU740318B2/en not_active Expired
- 1999-04-07 IL IL13858499A patent/IL138584A0/xx active IP Right Grant
- 1999-04-07 HU HU0102372A patent/HUP0102372A3/hu unknown
- 1999-04-07 CU CU20000220A patent/CU23049A3/es unknown
- 1999-04-07 SK SK1565-2000A patent/SK286407B6/sk not_active IP Right Cessation
- 1999-04-07 JP JP2000544665A patent/JP4590097B2/ja not_active Expired - Lifetime
- 1999-04-07 ES ES99920603T patent/ES2183548T3/es not_active Expired - Lifetime
- 1999-04-07 CN CNB998074950A patent/CN1159311C/zh not_active Expired - Lifetime
- 1999-04-07 PT PT99920603T patent/PT1080086E/pt unknown
- 1999-04-07 DE DE59902573T patent/DE59902573D1/de not_active Expired - Lifetime
- 1999-04-07 RU RU2000129148/04A patent/RU2245881C9/ru active
- 1999-04-07 BR BRPI9909730-3A patent/BR9909730B1/pt not_active IP Right Cessation
- 1999-04-07 AT AT99920603T patent/ATE223401T1/de active
- 1999-04-07 EP EP99920603A patent/EP1080086B1/de not_active Expired - Lifetime
- 1999-04-07 CA CA002328780A patent/CA2328780C/en not_active Expired - Lifetime
- 1999-04-15 PE PE1999000309A patent/PE20000427A1/es not_active IP Right Cessation
- 1999-04-16 GT GT199900056A patent/GT199900056A/es unknown
- 1999-04-16 SV SV1999000047A patent/SV1999000047A/es active IP Right Grant
- 1999-04-16 AR ARP990101779A patent/AR018187A1/es active IP Right Grant
- 1999-04-16 CO CO99022937A patent/CO5021127A1/es unknown
- 1999-04-16 MY MYPI99001481A patent/MY126527A/en unknown
- 1999-04-16 TW TW088106067A patent/TW548274B/zh active
- 1999-07-04 UA UA2000116511A patent/UA63998C2/uk unknown
2000
- 2000-09-20 IL IL138584A patent/IL138584A/en not_active IP Right Cessation
- 2000-09-26 ZA ZA200005136A patent/ZA200005136B/xx unknown
- 2000-09-29 BG BG104812A patent/BG64649B1/bg unknown
- 2000-10-17 NO NO20005215A patent/NO321985B1/no not_active IP Right Cessation
2004
- 2004-02-17 US US10/781,075 patent/US20040167135A1/en not_active Abandoned
- 2004-12-01 NO NO20045259A patent/NO329020B1/no not_active IP Right Cessation
2006
- 2006-12-15 US US11/639,955 patent/US7514565B2/en not_active Expired - Fee Related
2010
- 2010-07-23 JP JP2010165860A patent/JP5237332B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
NO20005215D0 (no)	2000-10-17
BG104812A (en)	2001-06-29
ID27263A (id)	2001-03-22
PL343481A1 (en)	2001-08-27
WO1999054326A8 (de)	1999-12-29
DE59902573D1 (en)	2002-10-10
HK1039119A1 (en)	2002-04-12
BRPI9917862A2 (2)	2010-12-07
SK15652000A3 (sk)	2001-04-09
UA63998C2 (uk)	2004-02-16
JP2002512243A (ja)	2002-04-23
RU2245881C9 (ru)	2006-02-10
US6696451B1 (en)	2004-02-24
NZ507569A (en)	2002-04-26
CA2328780C (en)	2008-09-23
CZ293482B6 (cs)	2004-05-12
HUP0102372A3 (en)	2003-01-28
BR9909730A (pt)	2000-12-19
US20070117812A1 (en)	2007-05-24
CO5021127A1 (es)	2001-03-27
CN1305471A (zh)	2001-07-25
HUP0102372A2 (hu)	2001-12-28
IL138584A (en)	2006-09-05
SK286407B6 (sk)	2008-09-05
EP1080086B1 (de)	2002-09-04
CZ20003871A3 (cs)	2001-01-17
US7514565B2 (en)	2009-04-07
WO1999054326A1 (de)	1999-10-28
BRPI9917862B1 (pt)	2013-05-07
KR100636771B1 (ko)	2006-10-23
AR018187A1 (es)	2001-10-31
AU3813399A (en)	1999-11-08
DE19817264A1 (de)	1999-10-21
ZA200005136B (en)	2001-03-02
GT199900056A (es)	2000-10-07
PL193898B1 (pl)	2007-03-30
TR200003011T2 (tr)	2001-01-22
AU740318B2 (en)	2001-11-01
JP4590097B2 (ja)	2010-12-01
PE20000427A1 (es)	2000-06-25
DK1080086T3 (da)	2002-12-23
CN1159311C (zh)	2004-07-28
SV1999000047A (es)	2000-06-23
ES2183548T3 (es)	2003-03-16
US20040167135A1 (en)	2004-08-26
PT1080086E (pt)	2002-12-31
NO20045259L (no)	2000-12-13
JP2010241837A (ja)	2010-10-28
TW548274B (en)	2003-08-21
EP1080086A1 (de)	2001-03-07
NO20005215L (no)	2000-12-13
BRPI9917862B8 (pt)	2021-05-25
MY126527A (en)	2006-10-31
JP5237332B2 (ja)	2013-07-17
BR9909730B1 (pt)	2012-09-04
KR20010042788A (ko)	2001-05-25
RU2245881C2 (ru)	2005-02-10
NO329020B1 (no)	2010-07-26
IL138584A0 (en)	2001-10-31
SI1080086T1 (en)	2003-02-28
ATE223401T1 (de)	2002-09-15
CU23049A3 (es)	2005-06-24
BG64649B1 (bg)	2005-10-31
CA2328780A1 (en)	1999-10-28

Legal Events

Date	Code	Title	Description
2013-06-17	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: BAYER INTELLECTUAL PROPERTY GMBH, DE
2019-05-13	MK1K	Patent expired

Publication	Publication Date	Title
NO321985B1 (no)	2006-07-31	Dihydropyrimidinforbindelser, fremgangsmater for fremstilling av slike, samt fremgangsmate for fremstilling av farmasoytiske preparater og anvendelse av forbindelsene i farmasoytiske preparater for behandling av virussykdommer, saerlig hepatitt B
US6436943B1 (en)	2002-08-20	Use of dihydropyrimidines as medicaments, and novel substances
RU2443703C2 (ru)	2012-02-27	Бром-фенил замещенные тиазолилдигидропиримидины
EP0579496B1 (en)	2001-11-14	4-Aminoquinazoline derivatives, and their use as medicine
US20030232842A1 (en)	2003-12-18	Medicaments against viral diseases
EP1877396B1 (de)	2009-02-18	Dipyridyl-dihydropyrazolone und ihre verwendung 4- (pyridin-3-yl) -2- (pyridin-2-yl) -1,2-dihydro-3h-pyrazol-3-on derivate als spezifische hemmstoffe der hif-prolyl-4-hydroxylasen zur behandlung kardiovaskulärer und hämatologischer erkrankungen
TW201922757A (zh)	2019-06-16	製備6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈的方法
WO2000058302A1 (de)	2000-10-05	Dihydropyrimidine und ihre verwendung zur behandlung von hepatitis b
CN113105394A (zh)	2021-07-13	一种含芳杂环结构的联苯二芳基嘧啶类衍生物及其制备方法和应用
Kouznetsov et al.	2004	4‐Aryl (benzyl) amino‐4‐heteroarylbut‐1‐enes as Building Blocks in Heterocyclic Synthesis. 4.1 Synthesis of 4, 6‐Dimethyl‐5‐nitro (amino)‐2‐pyridylquinolines and their Antiparasitic Activities
CZ395592A3 (en)	1994-02-16	4-aryl-3-(heteroarylureido)quinoline derivatives, process of their preparation and use
MX2015002046A (es)	2015-06-05	Tris-(hetero)aril-pirazoles y su uso.
CA1323876C (en)	1993-11-02	Dihydropyridine derivatives and pharmaceutical composition thereof
Liu et al.	2008	Synthesis and Anti‐HBV Activities Evaluation of New Ethyl 8‐Imidazolylmethyl‐7‐hydroxyquinoline‐3‐carboxylate Derivatives in vitro
JPH0240383A (ja)	1990-02-09	１，４−ジヒドロピリジン誘導体
NO782455L (no)	1979-01-16	Fremgangsmaate for fremstilling av farmakologisk aktive amidino-benzylpyrimidiner
US4347362A (en)	1982-08-31	1-Alkyl-4-amino-3-(3-aminotriazolo)-1,8 naphthyridine-2-ones
MXPA00010153A (en)	2001-09-07	Dihydropyrimidines
CA2561621A1 (en)	2005-10-20	Quinolone carboxylic acid derivatives for treatment of hyperproliferative conditions
KR19990023074A (ko)	1999-03-25	신규 피리돈카르복실산 유도체