CA2156919A1 - Pyrazolitriazines with interleukin-1 and tumour necrosis factor inhibitory activity - Google Patents
Pyrazolitriazines with interleukin-1 and tumour necrosis factor inhibitory activityInfo
- Publication number
- CA2156919A1 CA2156919A1 CA002156919A CA2156919A CA2156919A1 CA 2156919 A1 CA2156919 A1 CA 2156919A1 CA 002156919 A CA002156919 A CA 002156919A CA 2156919 A CA2156919 A CA 2156919A CA 2156919 A1 CA2156919 A1 CA 2156919A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- group
- carboxy
- hydroxy
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 102000000589 Interleukin-1 Human genes 0.000 title claims abstract description 8
- 108010002352 Interleukin-1 Proteins 0.000 title claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 title description 10
- 102000018594 Tumour necrosis factor Human genes 0.000 title 1
- 108050007852 Tumour necrosis factor Proteins 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 223
- 150000003839 salts Chemical class 0.000 claims abstract description 130
- 125000001424 substituent group Chemical group 0.000 claims abstract description 96
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 64
- 125000002252 acyl group Chemical group 0.000 claims abstract description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 27
- 125000003118 aryl group Chemical group 0.000 claims abstract description 27
- 239000001257 hydrogen Substances 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 239000003112 inhibitor Substances 0.000 claims abstract description 5
- -1 adamantanyl Chemical group 0.000 claims description 273
- 150000001875 compounds Chemical class 0.000 claims description 106
- 238000000034 method Methods 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000001589 carboacyl group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 33
- 238000006722 reduction reaction Methods 0.000 claims description 25
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 16
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 125000005059 halophenyl group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 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
- 238000003379 elimination reaction Methods 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 230000000069 prophylactic effect Effects 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- RDPSSWGBOSZKBI-UHFFFAOYSA-N 1-[7-(4-fluorophenyl)-8-pyridin-4-yl-3,4-dihydro-2h-pyrazolo[5,1-c][1,2,4]triazin-1-yl]-2-phenylethane-1,2-dione Chemical compound C1=CC(F)=CC=C1C1=NN(CCNN2C(=O)C(=O)C=3C=CC=CC=3)C2=C1C1=CC=NC=C1 RDPSSWGBOSZKBI-UHFFFAOYSA-N 0.000 claims description 2
- 125000006377 halopyridyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 25
- 125000001475 halogen functional group Chemical group 0.000 claims 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- DHCQXMWOKVTGDO-UHFFFAOYSA-N 1-[7-(4-fluorophenyl)-8-pyridin-4-yl-3,4-dihydro-2h-pyrazolo[5,1-c][1,2,4]triazin-1-yl]-2-phenylethane-1,2-dione;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NN(CCNN2C(=O)C(=O)C=3C=CC=CC=3)C2=C1C1=CC=NC=C1 DHCQXMWOKVTGDO-UHFFFAOYSA-N 0.000 claims 1
- LZCXMVNEZSVRSR-UHFFFAOYSA-N 1-[7-(4-fluorophenyl)-8-pyridin-4-yl-3,4-dihydro-2h-pyrazolo[5,1-c][1,2,4]triazin-1-yl]-2-phenylethane-1,2-dione;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC(F)=CC=C1C1=NN(CCNN2C(=O)C(=O)C=3C=CC=CC=3)C2=C1C1=CC=NC=C1 LZCXMVNEZSVRSR-UHFFFAOYSA-N 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000002704 decyl group Chemical group [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])* 0.000 claims 1
- 206010054094 Tumour necrosis Diseases 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 147
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- 238000006243 chemical reaction Methods 0.000 description 73
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 101150041968 CDC13 gene Proteins 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 239000000243 solution Substances 0.000 description 39
- 239000002904 solvent Substances 0.000 description 37
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000002253 acid Substances 0.000 description 31
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 22
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 125000005907 alkyl ester group Chemical group 0.000 description 13
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 description 13
- 230000002411 adverse Effects 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 125000005843 halogen group Chemical group 0.000 description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229910052697 platinum Inorganic materials 0.000 description 10
- 150000003217 pyrazoles Chemical class 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 229940073584 methylene chloride Drugs 0.000 description 9
- 125000004430 oxygen atom Chemical group O* 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- 239000012267 brine Substances 0.000 description 8
- 150000007522 mineralic acids Chemical class 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 8
- 238000010792 warming Methods 0.000 description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
- 150000001340 alkali metals Chemical class 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 239000007788 liquid Substances 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
- 229910052763 palladium Inorganic materials 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 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
- 238000004440 column chromatography Methods 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 235000019260 propionic acid Nutrition 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
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000002841 Lewis acid Substances 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 125000001624 naphthyl group Chemical group 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 229960003975 potassium Drugs 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000518994 Conta Species 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 150000003973 alkyl amines Chemical class 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 229910000042 hydrogen bromide Inorganic materials 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
- 229910052742 iron Inorganic materials 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
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- 230000037406 food intake Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
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- CTAPFRYPJLPFDF-UHFFFAOYSA-O hydron;1,2-oxazole Chemical compound C=1C=[NH+]OC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-O 0.000 description 1
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- 208000017169 kidney disease Diseases 0.000 description 1
- 125000000400 lauroyl 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])[H] 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
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- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- JVHPKYBRJQNPAT-UHFFFAOYSA-N n-cyclohexyl-2,2-diphenylethenimine Chemical compound C1CCCCC1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 JVHPKYBRJQNPAT-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
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- 125000001402 nonanoyl 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])[H] 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
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- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001312 palmitoyl 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])[H] 0.000 description 1
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
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- 239000002244 precipitate Substances 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- SRXDBMFVRUGWNJ-UHFFFAOYSA-N pyrazolo[5,1-c][1,2,4]triazine Chemical compound N1=NC=CN2N=CC=C21 SRXDBMFVRUGWNJ-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000003381 stabilizer Substances 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
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 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
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
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- 239000000080 wetting agent Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 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)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB93.03993.1 | 1993-02-26 | ||
| GB939303993A GB9303993D0 (en) | 1993-02-26 | 1993-02-26 | New heterocyclic derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2156919A1 true CA2156919A1 (en) | 1994-09-01 |
Family
ID=10731142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002156919A Abandoned CA2156919A1 (en) | 1993-02-26 | 1994-02-09 | Pyrazolitriazines with interleukin-1 and tumour necrosis factor inhibitory activity |
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 |
|---|---|---|---|---|
| ATE244219T1 (de) | 1996-04-25 | 2003-07-15 | Nissan Chemical Ind Ltd | Ethylenderivate und pestizide |
| AU7726898A (en) | 1997-05-22 | 1998-12-11 | G.D. Searle & Co. | Pyrazole derivatives as p38 kinase inhibitors |
| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| US6979686B1 (en) | 2001-12-07 | 2005-12-27 | Pharmacia Corporation | Substituted pyrazoles as p38 kinase inhibitors |
| JP4380803B2 (ja) | 1997-06-12 | 2009-12-09 | アベンテイス・フアルマ・リミテツド | イミダゾリル−環式アセタール |
| CA2294057A1 (en) | 1997-06-13 | 1998-12-17 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| US6455528B1 (en) | 1997-10-14 | 2002-09-24 | Mitsubishi Pharma Corporation | Piperazine compounds and medicinal use thereof |
| AR017219A1 (es) | 1997-12-19 | 2001-08-22 | Smithkline Beecham Corp | Derivados de imidazol 1,4,5 sustituidos, composiciones que los comprenden, procedimiento para la preparacion de dichos derivados, uso de los derivados parala manufactura de un medicamento |
| US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| EP1112070B1 (en) * | 1998-08-20 | 2004-05-12 | Smithkline Beecham Corporation | Novel substituted triazole compounds |
| WO2000025791A1 (en) | 1998-11-04 | 2000-05-11 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
| AU6729900A (en) * | 1999-08-31 | 2001-03-26 | Fujisawa Pharmaceutical Co., Ltd. | Organ preservatives |
| RU2264403C2 (ru) * | 1999-11-10 | 2005-11-20 | Орто-Макнейл Фармасьютикал, Инк. | Замещенные 2-арил-3-(гетероарил) имидазо [1,2-а] пиримидины, содержащие их фармацевтические композиции и связанные с ними способы |
| 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 |
| WO2001038314A1 (en) | 1999-11-23 | 2001-05-31 | Smithkline Beecham Corporation | 3,4-dihydro-(1h)quinazolin-2-one compounds as csbp/p38 kinase inhibitors |
| JP2003514899A (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 |
| JP2003528043A (ja) | 1999-11-23 | 2003-09-24 | 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 |
| 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 |
| EP1333833B1 (en) | 2000-10-23 | 2011-08-24 | GlaxoSmithKline LLC | Novel trisubstituted-8H-pyrido[2,3-d]pyrimidin-7-one compound for the treatment of CSBP/p38 kinase mediated diseases |
| 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 |
| JP2004518731A (ja) * | 2000-12-28 | 2004-06-24 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | 三環式ｃｒｆレセプターアンタゴニスト |
| NZ528525A (en) | 2001-05-24 | 2005-10-28 | Lilly Co Eli | Novel pyrrole derivatives as pharmaceutical agents |
| 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 |
| EP1534282B1 (en) | 2002-07-09 | 2006-12-27 | Boehringer Ingelheim Pharma GmbH & Co.KG | Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases |
| JP4494205B2 (ja) * | 2002-08-26 | 2010-06-30 | 武田薬品工業株式会社 | カルシウム受容体調節化合物およびその用途 |
| ATE490244T1 (de) * | 2003-01-27 | 2010-12-15 | Merck Sharp & Dohme | Substituierte pyrazole, zusammensetzungen,die solche verbindungen enthalten, und anwendungsverfahren |
| AU2005252183B2 (en) * | 2004-06-04 | 2008-07-17 | Merck Sharp & Dohme Corp. | 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 |
| AR053450A1 (es) | 2005-03-25 | 2007-05-09 | Glaxo Group Ltd | Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38 |
| US7423042B2 (en) | 2005-03-25 | 2008-09-09 | Glaxo Group Limited | Compounds |
| EP1865959A2 (en) | 2005-03-25 | 2007-12-19 | Glaxo Group Limited | Process for preparing pyridoý2,3-d¨pyrimidin-7-one and 3,4-dihydropyrimidoý4,5-d¨pyrimidin-2(1h)-one derivatives |
| UY29440A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| CA2614537A1 (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 |
| 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 |
| CN101441969B (zh) | 2007-11-23 | 2010-07-28 | 清华大学 | 场发射像素管 |
| EP2402344A1 (en) * | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazole fused bicyclic compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06502178A (ja) * | 1990-12-31 | 1994-03-10 | 藤沢薬品工業株式会社 | イミダゾトリアジン誘導体 |
| 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 IL IL108562A patent/IL108562A/xx not_active IP Right Cessation
- 1994-02-04 ZA ZA94787A patent/ZA94787B/xx unknown
- 1994-02-09 ES ES94906381T patent/ES2176235T3/es not_active Expired - Lifetime
- 1994-02-09 CN CN94191768A patent/CN1041929C/zh not_active Expired - Fee Related
- 1994-02-09 US US08/505,284 patent/US5670503A/en not_active Expired - Fee Related
- 1994-02-09 EP EP94906381A patent/EP0686156B1/en not_active Expired - Lifetime
- 1994-02-09 DK DK94906381T patent/DK0686156T3/da active
- 1994-02-09 RU RU95117872A patent/RU2124517C1/ru active
- 1994-02-09 WO PCT/JP1994/000213 patent/WO1994019350A1/en active IP Right Grant
- 1994-02-09 KR KR1019950703609A patent/KR100313615B1/ko not_active Expired - Fee Related
- 1994-02-09 CA CA002156919A patent/CA2156919A1/en not_active Abandoned
- 1994-02-09 DE DE69430988T patent/DE69430988T2/de not_active Expired - Fee Related
- 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 HU HU9402459A patent/HUT70832A/hu unknown
- 1994-02-09 JP JP51881094A patent/JP3569917B2/ja not_active Expired - Fee Related
- 1994-02-09 AU AU60108/94A patent/AU681625B2/en not_active Ceased
- 1994-02-18 TW TW083101366A patent/TW260669B/zh active
- 1994-02-24 MX MX9401408A patent/MX9401408A/es not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR100313615B1 (ko) | 2002-05-30 |
| AU6010894A (en) | 1994-09-14 |
| ZA94787B (en) | 1994-09-08 |
| PT686156E (pt) | 2002-12-31 |
| DK0686156T3 (da) | 2002-11-11 |
| RU2124517C1 (ru) | 1999-01-10 |
| ES2176235T3 (es) | 2002-12-01 |
| KR960701055A (ko) | 1996-02-24 |
| CN1041929C (zh) | 1999-02-03 |
| GB9303993D0 (en) | 1993-04-14 |
| DE69430988T2 (de) | 2002-11-28 |
| JPH08507056A (ja) | 1996-07-30 |
| EP0686156A1 (en) | 1995-12-13 |
| IL108562A (en) | 1997-06-10 |
| HUT70832A (en) | 1995-11-28 |
| EP0686156B1 (en) | 2002-07-17 |
| IL108562A0 (en) | 1994-05-30 |
| ATE220677T1 (de) | 2002-08-15 |
| TW260669B (OSRAM) | 1995-10-21 |
| HU9402459D0 (en) | 1994-11-28 |
| CN1120840A (zh) | 1996-04-17 |
| WO1994019350A1 (en) | 1994-09-01 |
| JP3569917B2 (ja) | 2004-09-29 |
| MX9401408A (es) | 1994-08-31 |
| US5670503A (en) | 1997-09-23 |
| DE69430988D1 (de) | 2002-08-22 |
| AU681625B2 (en) | 1997-09-04 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |