CN1041929C - 新的杂环衍生物及其制备方法和用途,和含该衍生物的药物组合物 - Google Patents
新的杂环衍生物及其制备方法和用途,和含该衍生物的药物组合物 Download PDFInfo
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- CN1041929C CN1041929C CN94191768A CN94191768A CN1041929C CN 1041929 C CN1041929 C CN 1041929C CN 94191768 A CN94191768 A CN 94191768A CN 94191768 A CN94191768 A CN 94191768A CN 1041929 C CN1041929 C CN 1041929C
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- 102000018594 Tumour necrosis factor Human genes 0.000 title claims description 15
- 108050007852 Tumour necrosis factor Proteins 0.000 title claims description 15
- 102000000589 Interleukin-1 Human genes 0.000 title claims description 12
- 108010002352 Interleukin-1 Proteins 0.000 title claims description 12
- 230000002401 inhibitory effect Effects 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 232
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 79
- 125000002252 acyl group Chemical group 0.000 claims abstract description 69
- 125000001424 substituent group Chemical group 0.000 claims abstract description 56
- 125000003118 aryl group Chemical group 0.000 claims abstract description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 32
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- -1 3-indanyl Chemical group 0.000 claims description 219
- 150000001875 compounds Chemical class 0.000 claims description 119
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 101
- 150000003839 salts Chemical class 0.000 claims description 96
- 238000006243 chemical reaction Methods 0.000 claims description 88
- 238000000034 method Methods 0.000 claims description 77
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 72
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 238000006722 reduction reaction Methods 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- UTBDLWOYFNBYNE-UHFFFAOYSA-N 1,2,4-triazine;hydrochloride Chemical compound Cl.C1=CN=NC=N1 UTBDLWOYFNBYNE-UHFFFAOYSA-N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000001118 alkylidene group Chemical group 0.000 claims description 6
- 238000003379 elimination reaction Methods 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000005936 piperidyl group Chemical group 0.000 claims description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000003435 aroyl group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 3
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 15
- AHIBWURJLGCHAY-UHFFFAOYSA-N [S].C1=CC=CC=C1 Chemical compound [S].C1=CC=CC=C1 AHIBWURJLGCHAY-UHFFFAOYSA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000000203 mixture Substances 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
- 239000002585 base Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 239000002253 acid Substances 0.000 description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 33
- 238000000354 decomposition reaction Methods 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 22
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- 238000002425 crystallisation Methods 0.000 description 19
- 230000008025 crystallization Effects 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 239000007788 liquid Substances 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 229960004756 ethanol Drugs 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 description 15
- 239000003513 alkali Substances 0.000 description 14
- 238000000605 extraction Methods 0.000 description 14
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 14
- 125000005907 alkyl ester group Chemical group 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- 229910052500 inorganic mineral Inorganic materials 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 235000010755 mineral Nutrition 0.000 description 12
- 239000011707 mineral Substances 0.000 description 12
- 150000003217 pyrazoles Chemical class 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
- 239000011737 fluorine Substances 0.000 description 11
- 229910052731 fluorine Inorganic materials 0.000 description 11
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 231100000989 no adverse effect Toxicity 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 229910052697 platinum Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 8
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 229910052728 basic metal Inorganic materials 0.000 description 7
- 150000003818 basic metals Chemical class 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000003810 ethyl acetate extraction Methods 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 150000007524 organic acids Chemical class 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
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- 238000010898 silica gel chromatography Methods 0.000 description 7
- 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 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 229910017052 cobalt Inorganic materials 0.000 description 6
- 239000010941 cobalt Substances 0.000 description 6
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- SRXDBMFVRUGWNJ-UHFFFAOYSA-N pyrazolo[5,1-c][1,2,4]triazine Chemical compound N1=NC=CN2N=CC=C21 SRXDBMFVRUGWNJ-UHFFFAOYSA-N 0.000 description 6
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000002841 Lewis acid Substances 0.000 description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
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- 239000000725 suspension Substances 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000002140 halogenating effect Effects 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 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 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 229910052759 nickel Inorganic materials 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
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- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- XIUROWKZWPIAIB-UHFFFAOYSA-N sulfotep Chemical compound CCOP(=S)(OCC)OP(=S)(OCC)OCC XIUROWKZWPIAIB-UHFFFAOYSA-N 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004149 thio group Chemical group *S* 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical class OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 description 1
- 125000000297 undecanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB93039931 | 1993-02-26 | ||
| GB9303993-1 | 1993-02-26 | ||
| GB939303993A GB9303993D0 (en) | 1993-02-26 | 1993-02-26 | New heterocyclic derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1120840A CN1120840A (zh) | 1996-04-17 |
| CN1041929C true CN1041929C (zh) | 1999-02-03 |
Family
ID=10731142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94191768A Expired - Fee Related CN1041929C (zh) | 1993-02-26 | 1994-02-09 | 新的杂环衍生物及其制备方法和用途,和含该衍生物的药物组合物 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5670503A (OSRAM) |
| EP (1) | EP0686156B1 (OSRAM) |
| JP (1) | JP3569917B2 (OSRAM) |
| KR (1) | KR100313615B1 (OSRAM) |
| CN (1) | CN1041929C (OSRAM) |
| AT (1) | ATE220677T1 (OSRAM) |
| AU (1) | AU681625B2 (OSRAM) |
| CA (1) | CA2156919A1 (OSRAM) |
| DE (1) | DE69430988T2 (OSRAM) |
| DK (1) | DK0686156T3 (OSRAM) |
| ES (1) | ES2176235T3 (OSRAM) |
| GB (1) | GB9303993D0 (OSRAM) |
| HU (1) | HUT70832A (OSRAM) |
| IL (1) | IL108562A (OSRAM) |
| MX (1) | MX9401408A (OSRAM) |
| PT (1) | PT686156E (OSRAM) |
| RU (1) | RU2124517C1 (OSRAM) |
| TW (1) | TW260669B (OSRAM) |
| WO (1) | WO1994019350A1 (OSRAM) |
| ZA (1) | ZA94787B (OSRAM) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69723267T2 (de) | 1996-04-25 | 2004-04-22 | Nissan Chemical Industries, Ltd. | Ethylenderivate und pestizide |
| JP2002502380A (ja) | 1997-05-22 | 2002-01-22 | ジー．ディー．サール アンド カンパニー | ｐ３８キナーゼ阻害剤としてのピラゾール誘導体 |
| US6979686B1 (en) | 2001-12-07 | 2005-12-27 | Pharmacia Corporation | Substituted pyrazoles as p38 kinase inhibitors |
| US6514977B1 (en) * | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| PT988301E (pt) | 1997-06-12 | 2006-10-31 | Aventis Pharma Ltd | Acetais ciclicos de imidazolilo |
| CA2294057A1 (en) | 1997-06-13 | 1998-12-17 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| EP1029851B1 (en) | 1997-10-14 | 2005-04-20 | Mitsubishi Pharma Corporation | Piperazine compounds and medicinal use thereof |
| JP2001526230A (ja) | 1997-12-19 | 2001-12-18 | スミスクライン・ビーチャム・コーポレイション | ヘテロアリール置換イミダゾール化合物、その医薬組成物および使用 |
| US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| ATE266399T1 (de) * | 1998-08-20 | 2004-05-15 | Smithkline Beecham Corp | Neue substituierte triazolverbindungen |
| WO2000025791A1 (en) | 1998-11-04 | 2000-05-11 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
| EP1208748A4 (en) * | 1999-08-31 | 2002-11-20 | Fujisawa Pharmaceutical Co | PRESERVATIVES FOR ORGANS |
| AU784484B2 (en) * | 1999-11-10 | 2006-04-13 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted 2-aryl-3(heteroaryl)-imidazo(1,2-a) pyrimidines, and related pharmaceutical compositions and methods |
| US7253169B2 (en) * | 1999-11-12 | 2007-08-07 | Gliamed, Inc. | Aza compounds, pharmaceutical compositions and methods of use |
| US6417189B1 (en) * | 1999-11-12 | 2002-07-09 | Gpi Nil Holdings, Inc. | AZA compounds, pharmaceutical compositions and methods of use |
| US6759410B1 (en) | 1999-11-23 | 2004-07-06 | Smithline Beecham Corporation | 3,4-dihydro-(1H)-quinazolin-2-ones and their use as CSBP/p38 kinase inhibitors |
| JP2003514900A (ja) | 1999-11-23 | 2003-04-22 | スミスクライン・ビーチャム・コーポレイション | ＣＳＢＰ／ｐ３８キナーゼ阻害剤としての３，４−ジヒドロ−（１Ｈ）−キナゾリン−２−オン化合物 |
| ES2249309T3 (es) | 1999-11-23 | 2006-04-01 | Smithkline Beecham Corp | Compuestos de 3,4-dihidro-(1h)quinazolin-2-ona como inhibidores de csbp/p39 kinasa. |
| AU1781601A (en) | 1999-11-23 | 2001-06-04 | Smithkline Beecham Corporation | 3,4-dihydro-(1h)quinazolin-2-one compounds as csbp/p38 kinase inhibitors |
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| JP4524072B2 (ja) | 2000-10-23 | 2010-08-11 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 新規化合物 |
| RU2316556C2 (ru) * | 2000-11-17 | 2008-02-10 | Бристол-Маерс Сквибб Компани | СПОСОБЫ ЛЕЧЕНИЯ СОСТОЯНИЙ, ОБУСЛОВЛЕННЫХ p38 КИНАЗАМИ, И ПИРРОЛОТРИАЗИНОВЫЕ СОЕДИНЕНИЯ, ПРИМЕНИМЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ КИНАЗ |
| WO2002064592A1 (en) * | 2000-12-28 | 2002-08-22 | Neurocrine Biosciences, Inc. | Tricyclic crf receptor antagonists |
| KR100861630B1 (ko) * | 2001-05-24 | 2008-10-07 | 일라이 릴리 앤드 캄파니 | 제약 제제로서의 신규 피롤 유도체 |
| US6821971B2 (en) * | 2001-09-20 | 2004-11-23 | The Procter & Gamble Company | Fused pyrazolone compounds which inhibit the release of inflammatory cytokines |
| US7629350B2 (en) | 2002-04-19 | 2009-12-08 | Smithkline Beecham Corporation | Compounds |
| ES2278170T3 (es) | 2002-07-09 | 2007-08-01 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Composiciones farmaceuticas de anticolinergicos e inhibidores de la quinasa p38 en el tratamiento de enfermedades respiratorias. |
| BRPI0313880B8 (pt) * | 2002-08-26 | 2021-05-25 | Takeda Pharmaceuticals Co | composto |
| EP1590336B1 (en) * | 2003-01-27 | 2010-12-01 | Merck Sharp & Dohme Corp. | Substituted pyrazoles, compositions containing such compounds and methods of use |
| NZ551405A (en) * | 2004-06-04 | 2009-06-26 | Merck & Co Inc | Pyrazole derivatives, compositions containing such compounds and methods of use |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| AR053346A1 (es) | 2005-03-25 | 2007-05-02 | Glaxo Group Ltd | Compuesto derivado de 8h -pirido (2,3-d) pirimidin -7 ona 2,4,8- trisustituida composicion farmaceutica y uso para preparar una composicion para tratamiento y profilxis de una enfermedad mediada por la quinasa csbp/ rk/p38 |
| EA200702073A1 (ru) | 2005-03-25 | 2008-12-30 | Глэксо Груп Лимитед | Способ получения пиридо[2,3-d]пиримидин-7-оновых и 3,4-дигидропиримидо[4,5-d]пиримидин-2(1н)-оновых производных |
| PE20100741A1 (es) | 2005-03-25 | 2010-11-25 | Glaxo Group Ltd | COMPUESTOS DERIVADOS DE 3,4-DIHIDROPIRIMIDO[4,5-d]PIRIMIDIN-2(1H)-ONA COMO INHIBIDORES DE QUINASA p38 |
| US20090137550A1 (en) | 2005-03-25 | 2009-05-28 | Glaxo Group Limited | Novel Compounds |
| WO2007015999A2 (en) * | 2005-07-26 | 2007-02-08 | Merck & Co., Inc. | Process for synthesizing a substituted pyrazole |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| US20110195962A1 (en) * | 2007-08-16 | 2011-08-11 | Alcon Research, Ltd. | Use of multi-pharmacophore compounds to treat nasal disorders |
| JP2010540451A (ja) * | 2007-09-20 | 2010-12-24 | ワイス・エルエルシー | ピラゾロ［５，１−ｃ］［１，２，４］トリアジン、その調製法および使用法 |
| CN101441969B (zh) | 2007-11-23 | 2010-07-28 | 清华大学 | 场发射像素管 |
| CN101441972B (zh) | 2007-11-23 | 2011-01-26 | 鸿富锦精密工业（深圳）有限公司 | 场发射像素管 |
| EP2402344A1 (en) * | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazole fused bicyclic compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992012154A1 (en) * | 1990-12-31 | 1992-07-23 | Fujisawa Pharmaceutical Co., Ltd. | Imidazotriazine derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5356897A (en) * | 1991-09-09 | 1994-10-18 | Fujisawa Pharmaceutical Co., Ltd. | 3-(heteroaryl)-pyrazololi[1,5-a]pyrimidines |
-
1993
- 1993-02-26 GB GB939303993A patent/GB9303993D0/en active Pending
-
1994
- 1994-02-04 ZA ZA94787A patent/ZA94787B/xx unknown
- 1994-02-04 IL IL108562A patent/IL108562A/xx not_active IP Right Cessation
- 1994-02-09 DK DK94906381T patent/DK0686156T3/da active
- 1994-02-09 DE DE69430988T patent/DE69430988T2/de not_active Expired - Fee Related
- 1994-02-09 WO PCT/JP1994/000213 patent/WO1994019350A1/en active IP Right Grant
- 1994-02-09 EP EP94906381A patent/EP0686156B1/en not_active Expired - Lifetime
- 1994-02-09 US US08/505,284 patent/US5670503A/en not_active Expired - Fee Related
- 1994-02-09 HU HU9402459A patent/HUT70832A/hu unknown
- 1994-02-09 AT AT94906381T patent/ATE220677T1/de not_active IP Right Cessation
- 1994-02-09 PT PT94906381T patent/PT686156E/pt unknown
- 1994-02-09 ES ES94906381T patent/ES2176235T3/es not_active Expired - Lifetime
- 1994-02-09 KR KR1019950703609A patent/KR100313615B1/ko not_active Expired - Fee Related
- 1994-02-09 CN CN94191768A patent/CN1041929C/zh not_active Expired - Fee Related
- 1994-02-09 AU AU60108/94A patent/AU681625B2/en not_active Ceased
- 1994-02-09 CA CA002156919A patent/CA2156919A1/en not_active Abandoned
- 1994-02-09 JP JP51881094A patent/JP3569917B2/ja not_active Expired - Fee Related
- 1994-02-09 RU RU95117872A patent/RU2124517C1/ru active
- 1994-02-18 TW TW083101366A patent/TW260669B/zh active
- 1994-02-24 MX MX9401408A patent/MX9401408A/es not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992012154A1 (en) * | 1990-12-31 | 1992-07-23 | Fujisawa Pharmaceutical Co., Ltd. | Imidazotriazine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA94787B (en) | 1994-09-08 |
| AU681625B2 (en) | 1997-09-04 |
| CA2156919A1 (en) | 1994-09-01 |
| DK0686156T3 (da) | 2002-11-11 |
| DE69430988T2 (de) | 2002-11-28 |
| AU6010894A (en) | 1994-09-14 |
| KR960701055A (ko) | 1996-02-24 |
| JP3569917B2 (ja) | 2004-09-29 |
| DE69430988D1 (de) | 2002-08-22 |
| WO1994019350A1 (en) | 1994-09-01 |
| ATE220677T1 (de) | 2002-08-15 |
| PT686156E (pt) | 2002-12-31 |
| GB9303993D0 (en) | 1993-04-14 |
| EP0686156B1 (en) | 2002-07-17 |
| HU9402459D0 (en) | 1994-11-28 |
| IL108562A0 (en) | 1994-05-30 |
| CN1120840A (zh) | 1996-04-17 |
| KR100313615B1 (ko) | 2002-05-30 |
| US5670503A (en) | 1997-09-23 |
| TW260669B (OSRAM) | 1995-10-21 |
| HUT70832A (en) | 1995-11-28 |
| JPH08507056A (ja) | 1996-07-30 |
| RU2124517C1 (ru) | 1999-01-10 |
| MX9401408A (es) | 1994-08-31 |
| IL108562A (en) | 1997-06-10 |
| EP0686156A1 (en) | 1995-12-13 |
| ES2176235T3 (es) | 2002-12-01 |
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