JP4590097B2 - ジヒドロピリミジン類 - Google Patents
ジヒドロピリミジン類 Download PDFInfo
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- JP4590097B2 JP4590097B2 JP2000544665A JP2000544665A JP4590097B2 JP 4590097 B2 JP4590097 B2 JP 4590097B2 JP 2000544665 A JP2000544665 A JP 2000544665A JP 2000544665 A JP2000544665 A JP 2000544665A JP 4590097 B2 JP4590097 B2 JP 4590097B2
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- 150000001875 compounds Chemical class 0.000 claims description 47
- -1 2-chloro-4-fluorophenyl Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 150000001409 amidines Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 239000001257 hydrogen Substances 0.000 description 22
- 229910052739 hydrogen Inorganic materials 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 125000004076 pyridyl group Chemical group 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 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
- 125000000217 alkyl group Chemical group 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical group 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- ATUOLSDAAPMVJJ-UHFFFAOYSA-N 3,5-dichloropyridine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C(Cl)=C1 ATUOLSDAAPMVJJ-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 108020004414 DNA Proteins 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 208000002672 hepatitis B Diseases 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 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 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000003814 drug Substances 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 125000001425 triazolyl group Chemical group 0.000 description 4
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 241000700721 Hepatitis B virus Species 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
- 241000700605 Viruses Species 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 229920001778 nylon Polymers 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- WLBIFECTHKFYKV-UHFFFAOYSA-N 3,5-difluoropyridine-2-carbonitrile Chemical compound FC1=CN=C(C#N)C(F)=C1 WLBIFECTHKFYKV-UHFFFAOYSA-N 0.000 description 2
- QVGBDRDOWKIYHK-UHFFFAOYSA-N 3-fluoro-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=CC(F)=C1 QVGBDRDOWKIYHK-UHFFFAOYSA-N 0.000 description 2
- VZFPSCNTFBJZHB-UHFFFAOYSA-N 3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC=CN=C1C#N VZFPSCNTFBJZHB-UHFFFAOYSA-N 0.000 description 2
- PGSRJYWURHANOG-UHFFFAOYSA-N 3-fluoropyridine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NC=CC=C1F PGSRJYWURHANOG-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 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
- YBAZKCWCUHCSHJ-UHFFFAOYSA-N BrC1=C(C=CC=C1)C1N=C(NC(=C1C(=O)O)C)C1=NC=CC=C1F Chemical compound BrC1=C(C=CC=C1)C1N=C(NC(=C1C(=O)O)C)C1=NC=CC=C1F YBAZKCWCUHCSHJ-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 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
- 230000001154 acute effect Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 208000016350 chronic hepatitis B virus infection Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
- 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 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 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
- 239000002904 solvent Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 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
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 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
- CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 1
- IQPCUXVRFBIAOL-UHFFFAOYSA-N 4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoropyridin-2-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound N1C(C)=C(C(O)=O)C(C=2C(=CC(F)=CC=2)Cl)N=C1C1=NC=C(F)C=C1F IQPCUXVRFBIAOL-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
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Classifications
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- 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
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- 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
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- 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
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- 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
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19817264A DE19817264A1 (de) | 1998-04-18 | 1998-04-18 | Neue Dihydropyrimidine |
| DE19817264.8 | 1998-04-18 | ||
| PCT/EP1999/002344 WO1999054326A1 (de) | 1998-04-18 | 1999-04-07 | Dihydropyrimidine |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010165860A Division JP5237332B2 (ja) | 1998-04-18 | 2010-07-23 | ジヒドロピリミジン類 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002512243A JP2002512243A (ja) | 2002-04-23 |
| JP2002512243A5 JP2002512243A5 (enExample) | 2006-06-01 |
| JP4590097B2 true JP4590097B2 (ja) | 2010-12-01 |
Family
ID=7864972
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000544665A Expired - Lifetime JP4590097B2 (ja) | 1998-04-18 | 1999-04-07 | ジヒドロピリミジン類 |
| JP2010165860A Expired - Lifetime JP5237332B2 (ja) | 1998-04-18 | 2010-07-23 | ジヒドロピリミジン類 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010165860A Expired - Lifetime JP5237332B2 (ja) | 1998-04-18 | 2010-07-23 | ジヒドロピリミジン類 |
Country Status (36)
Families Citing this family (43)
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| WO2000058302A1 (de) * | 1999-03-25 | 2000-10-05 | Bayer Aktiengesellschaft | Dihydropyrimidine und ihre verwendung zur behandlung von hepatitis b |
| WO2000078730A1 (en) | 1999-06-23 | 2000-12-28 | Ajinomoto Co., Inc. | Novel dihydropyrimidine derivatives |
| 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 |
| DE10013125A1 (de) * | 2000-03-17 | 2001-09-20 | Bayer Ag | Arzneimittel gegen virale Erkrankungen |
| DE10013126A1 (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 |
| PT2514750E (pt) * | 2007-06-18 | 2014-01-23 | Sunshine Lake Pharma Co Ltd | Tiazolil dihidropirimidinas substituídas com bromo-fenilo |
| NZ582443A (en) | 2007-07-12 | 2011-04-29 | 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 |
| MY182403A (en) * | 2012-08-24 | 2021-01-25 | Sunshine Lake Pharma Co Ltd | Dihydropyrimidine compounds and their application in pharmaceuticals |
| CA2881322A1 (en) | 2012-09-10 | 2014-03-13 | 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 |
| HK1215030A1 (zh) * | 2012-11-09 | 2016-08-12 | Indiana University Research And Technology Corporation | 用於hbv組裝效應劑的替代用途 |
| BR102014028162A2 (pt) * | 2013-11-12 | 2015-09-08 | Dow Agrosciences Llc | processo para fluoração de compostos |
| CA2920415A1 (en) | 2013-11-19 | 2015-05-28 | Sunshine Lake Pharma Co., Ltd. | Dihydropyrimidine compounds and their application in pharmaceuticals |
| KR102284944B1 (ko) | 2013-11-27 | 2021-08-03 | 선샤인 레이크 파르마 컴퍼니 리미티드 | 다이하이드로피리미딘 유도체 및 이의 중간산물의 제조 방법 |
| MX2016012573A (es) | 2014-03-28 | 2018-02-19 | Sunshine Lake Pharma Co Ltd | Compuestos de dihidropirimidina y su aplicacion en productos farmaceuticos. |
| 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 |
| EP3150600B1 (en) * | 2014-05-30 | 2018-06-27 | Qilu Pharmaceutical Co., Ltd. | Dihydropyrimido loop derivative as hbv inhibitor |
| AU2016214799A1 (en) | 2015-02-07 | 2017-06-15 | Sunshine Lake Pharma Co., Ltd. | Complexes and salts of dihydropyrimidine derivatives and their application in pharmaceuticals |
| EP3645516A4 (en) | 2017-06-27 | 2021-07-07 | Janssen Pharmaceutica NV | HETEROARYLDIHYDROPYRIMIDE DERIVATIVES AND METHODS OF TREATMENT OF 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 |
| EA202091113A1 (ru) | 2017-11-02 | 2020-08-28 | Айкурис Гмбх Унд Ко. Кг | Новые высокоактивные аминотиазолзамещенные индол-2-карбоксамиды, активные в отношении вируса гепатита b (hbv) |
| MX2020004838A (es) | 2017-11-02 | 2020-10-16 | Aicuris Gmbh & Co Kg | Nuevas indol-2-carboxamidas sustituidas con pirazolopiperidina, de alta actividad, activas contra el virus de la hepatitis b (vhb). |
| EP3790866A4 (en) * | 2018-05-08 | 2022-03-02 | Janssen Sciences Ireland Unlimited Company | DIHYDROPYRIMIDINE DERIVATIVES AND THEIR USES IN THE TREATMENT OF HEPATITIS B VIRUS INFECTION OR HEPATITIS B VIRUS INDUCED DISEASES |
| 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 |
| 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) |
| US20220009945A1 (en) * | 2018-11-02 | 2022-01-13 | Aicuris Gmbh & Co. Kg | Novel urea 6,7-dihydro-4h-thiazole[5,4-c]pyridines active against the hepatitis b virus (hbv) |
| PY1991611A (es) | 2018-11-02 | 2022-03-14 | Aicuris Gmbh & Co Kg | Nueva urea 6,7-dihidro-4h-pirazolo [1,5-a] pirazinas 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) |
| 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) |
| AR117188A1 (es) | 2018-11-02 | 2021-07-21 | Aicuris Gmbh & Co Kg | Derivados de urea 6,7-dihidro-4h-pirazolo[1,5-a]pirazinas activas contra el virus de la hepatitis b (vhb) |
| CA3124317A1 (en) | 2018-12-20 | 2020-06-25 | Janssen Pharmaceutica Nv | Heteroaryldihydropyrimidine derivatives and methods of treating hepatitis b infections |
| EP3962909B1 (en) | 2019-04-30 | 2023-10-04 | AiCuris GmbH & Co. KG | Novel oxalyl piperazines active against the hepatitis b virus (hbv) |
| MX2021013086A (es) | 2019-04-30 | 2021-11-17 | Aicuris Gmbh & Co Kg | Nuevas fenil y piridil ureas activas contra el virus de la hepatitis b (vhb). |
| US20220306647A1 (en) | 2019-04-30 | 2022-09-29 | Aicuris Gmbh & Co. Kg | Novel indole-2-carboxamides active against the hepatitus b virus (hbv) |
| KR20220002498A (ko) | 2019-04-30 | 2022-01-06 | 아이쿠리스 게엠베하 운트 코. 카게 | B형 간염 바이러스 (hbv)에 대해 활성인 신규 인돌리진-2-카르복스아미드 |
| 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL130304C (enExample) * | 1964-02-12 | |||
| CH550189A (de) | 1971-01-08 | 1974-06-14 | Ciba Geigy Ag | Verfahren zur herstellung von neuen dibenzo (b,f) thiepincarbonsaeuren. |
| CH569043A5 (enExample) | 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 |
| EP0941222A2 (en) | 1996-11-12 | 1999-09-15 | Novartis AG | Pyrazole derivatives useful as herbicides |
| SE9702564D0 (sv) | 1997-07-02 | 1997-07-02 | Astra Ab | New compounds |
-
1998
- 1998-04-18 DE DE19817264A patent/DE19817264A1/de not_active Withdrawn
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1999
- 1999-04-07 BR BRPI9909730-3A patent/BR9909730B1/pt not_active IP Right Cessation
- 1999-04-07 DE DE59902573T patent/DE59902573D1/de not_active Expired - Lifetime
- 1999-04-07 ID IDW20002111A patent/ID27263A/id unknown
- 1999-04-07 SK SK1565-2000A patent/SK286407B6/sk not_active IP Right Cessation
- 1999-04-07 NZ NZ507569A patent/NZ507569A/en not_active IP Right Cessation
- 1999-04-07 AT AT99920603T patent/ATE223401T1/de active
- 1999-04-07 ES ES99920603T patent/ES2183548T3/es not_active Expired - Lifetime
- 1999-04-07 EP EP99920603A patent/EP1080086B1/de not_active Expired - Lifetime
- 1999-04-07 TR TR2000/03011T patent/TR200003011T2/xx unknown
- 1999-04-07 CU CU20000220A patent/CU23049A3/es unknown
- 1999-04-07 CZ CZ20003871A patent/CZ293482B6/cs not_active IP Right Cessation
- 1999-04-07 HU HU0102372A patent/HUP0102372A3/hu unknown
- 1999-04-07 WO PCT/EP1999/002344 patent/WO1999054326A1/de not_active Ceased
- 1999-04-07 KR KR1020007011527A patent/KR100636771B1/ko not_active Expired - Lifetime
- 1999-04-07 SI SI9930139T patent/SI1080086T1/xx unknown
- 1999-04-07 PL PL99343481A patent/PL193898B1/pl unknown
- 1999-04-07 JP JP2000544665A patent/JP4590097B2/ja not_active Expired - Lifetime
- 1999-04-07 CN CNB998074950A patent/CN1159311C/zh not_active Expired - Lifetime
- 1999-04-07 CA CA002328780A patent/CA2328780C/en not_active Expired - Lifetime
- 1999-04-07 IL IL13858499A patent/IL138584A0/xx active IP Right Grant
- 1999-04-07 RU RU2000129148/04A patent/RU2245881C9/ru active
- 1999-04-07 BR BRPI9917862A patent/BRPI9917862B8/pt not_active IP Right Cessation
- 1999-04-07 PT PT99920603T patent/PT1080086E/pt unknown
- 1999-04-07 DK DK99920603T patent/DK1080086T3/da active
- 1999-04-07 AU AU38133/99A patent/AU740318B2/en not_active Expired
- 1999-04-07 US US09/673,592 patent/US6696451B1/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 AR ARP990101779A patent/AR018187A1/es active IP Right Grant
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- 1999-04-16 SV SV1999000047A patent/SV1999000047A/es active IP Right Grant
- 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
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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
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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
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2006
- 2006-12-15 US US11/639,955 patent/US7514565B2/en not_active Expired - Fee Related
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2010
- 2010-07-23 JP JP2010165860A patent/JP5237332B2/ja not_active Expired - Lifetime
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