SK8432000A3 - Adamantane derivatives - Google Patents
Adamantane derivatives Download PDFInfo
- Publication number
- SK8432000A3 SK8432000A3 SK843-2000A SK8432000A SK8432000A3 SK 8432000 A3 SK8432000 A3 SK 8432000A3 SK 8432000 A SK8432000 A SK 8432000A SK 8432000 A3 SK8432000 A3 SK 8432000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- dec
- tricyclo
- ylmethyl
- benzamide
- chloro
- Prior art date
Links
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 title abstract description 4
- 229940052761 dopaminergic adamantane derivative Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 238000000034 method Methods 0.000 claims abstract description 40
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 125000001424 substituent group Chemical group 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 9
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 4
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- -1 dec-1-ylmethyl Chemical group 0.000 claims description 279
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 74
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 239000011570 nicotinamide Substances 0.000 claims description 34
- 229960003966 nicotinamide Drugs 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000012453 solvate Substances 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 239000000460 chlorine Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 206010062016 Immunosuppression Diseases 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004266 aziridin-1-yl group Chemical group [H]C1([H])N(*)C1([H])[H] 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- LJAKORSHDLBREQ-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-(4-methoxyphenyl)sulfanylpyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1SC1=NC=CC=C1C(=O)NCC1(C2)CC(C3)CC2CC3C1 LJAKORSHDLBREQ-UHFFFAOYSA-N 0.000 claims description 2
- BBHOQWJUKCPXPF-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-(4-methylphenyl)sulfanylpyridine-3-carboxamide Chemical compound C1=CC(C)=CC=C1SC1=NC=CC=C1C(=O)NCC1(C2)CC(C3)CC2CC3C1 BBHOQWJUKCPXPF-UHFFFAOYSA-N 0.000 claims description 2
- RIOFIRHOHRZKGV-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-methylsulfinylpyridine-3-carboxamide Chemical compound CS(=O)C1=NC=CC=C1C(=O)NCC1(C2)CC(C3)CC2CC3C1 RIOFIRHOHRZKGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- HAGIMAAESIEYIZ-UHFFFAOYSA-N n-(1-adamantylmethyl)-6-methyl-2-methylsulfanylpyridine-3-carboxamide Chemical compound CSC1=NC(C)=CC=C1C(=O)NCC1(C2)CC(C3)CC2CC3C1 HAGIMAAESIEYIZ-UHFFFAOYSA-N 0.000 claims 1
- 239000011664 nicotinic acid Substances 0.000 claims 1
- 229960003512 nicotinic acid Drugs 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- QXULVSDEUURLJC-UHFFFAOYSA-N pyridine;pyridine-3-carboxamide Chemical compound C1=CC=NC=C1.NC(=O)C1=CC=CN=C1 QXULVSDEUURLJC-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 159
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- 239000007787 solid Substances 0.000 description 95
- 239000000243 solution Substances 0.000 description 93
- 238000002844 melting Methods 0.000 description 75
- 230000008018 melting Effects 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 56
- 238000005160 1H NMR spectroscopy Methods 0.000 description 52
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- 238000001228 spectrum Methods 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- XSOHXMFFSKTSIT-UHFFFAOYSA-N 1-adamantylmethanamine Chemical compound C1C(C2)CC3CC2CC1(CN)C3 XSOHXMFFSKTSIT-UHFFFAOYSA-N 0.000 description 37
- 238000001819 mass spectrum Methods 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 30
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 30
- 238000010898 silica gel chromatography Methods 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- 239000011734 sodium Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000012458 free base Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 8
- 101710189965 P2X purinoceptor 7 Proteins 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 150000003457 sulfones Chemical class 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 7
- XZRHNAFEYMSXRG-UHFFFAOYSA-N 2,5-dimethylbenzoic acid Chemical compound CC1=CC=C(C)C(C(O)=O)=C1 XZRHNAFEYMSXRG-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
- GKRPMKRIQVEDAE-UHFFFAOYSA-N 2-(1-adamantyl)ethanamine;hydrochloride Chemical compound Cl.C1C(C2)CC3CC2CC1(CCN)C3 GKRPMKRIQVEDAE-UHFFFAOYSA-N 0.000 description 4
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylamino-1-chloro-ethane hydrochloride Natural products CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- BURJIEWNHIKROD-FWDYTFEUSA-N [[(2r,3r,4r,5s)-5-(6-aminopurin-9-yl)-4,5-dibenzoyl-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C([C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@]1(N1C=2N=CN=C(C=2N=C1)N)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 BURJIEWNHIKROD-FWDYTFEUSA-N 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical class [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000004808 supercritical fluid chromatography Methods 0.000 description 4
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 3
- WMPVKMPRBLTWIN-UHFFFAOYSA-N 3,5-dimethoxy-2-methylbenzoic acid Chemical compound COC1=CC(OC)=C(C)C(C(O)=O)=C1 WMPVKMPRBLTWIN-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 3
- 229960005542 ethidium bromide Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 3
- VKFPFSZMRAIQMG-UHFFFAOYSA-N n-(1-adamantylmethyl)-3,5-dimethoxy-2-methylbenzamide Chemical compound COC1=CC(OC)=C(C)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 VKFPFSZMRAIQMG-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
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- 239000008187 granular material Substances 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004871 hexylcarbonyl group Chemical group C(CCCCC)C(=O)* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
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- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- FUWDNMISAQCVMT-UHFFFAOYSA-N methyl 3,5-dimethoxy-2-methylbenzoate Chemical compound COC(=O)C1=CC(OC)=CC(OC)=C1C FUWDNMISAQCVMT-UHFFFAOYSA-N 0.000 description 1
- QAWFLJGZSZIZHO-UHFFFAOYSA-N methyl 4-bromobutanoate Chemical compound COC(=O)CCCBr QAWFLJGZSZIZHO-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
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- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- CAYNAIIKEMTKCM-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-chloro-5-(methylamino)benzamide Chemical compound CNC1=CC=C(Cl)C(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1 CAYNAIIKEMTKCM-UHFFFAOYSA-N 0.000 description 1
- WECQPSRETWGYSU-UHFFFAOYSA-N n-(1-adamantylmethyl)-2-methylsulfanylpyridine-3-carboxamide Chemical compound CSC1=NC=CC=C1C(=O)NCC1(C2)CC(C3)CC2CC3C1 WECQPSRETWGYSU-UHFFFAOYSA-N 0.000 description 1
- SDNJNDFHCODQDQ-UHFFFAOYSA-N n-(2-ethylphenyl)-2-[[2-[(2-ethylphenyl)carbamoyl]phenyl]disulfanyl]benzamide Chemical compound CCC1=CC=CC=C1NC(=O)C1=CC=CC=C1SSC1=CC=CC=C1C(=O)NC1=CC=CC=C1CC SDNJNDFHCODQDQ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-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
- GSJJCZSHYJNRPN-UHFFFAOYSA-N tert-butyl n-(2-sulfanylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCS GSJJCZSHYJNRPN-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
- C07D203/14—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom with carbocyclic rings directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/60—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
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- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9704544A SE9704544D0 (sv) | 1997-12-05 | 1997-12-05 | Novel compounds |
PCT/SE1998/002188 WO1999029661A1 (fr) | 1997-12-05 | 1998-12-01 | Derives d'adamantane |
Publications (1)
Publication Number | Publication Date |
---|---|
SK8432000A3 true SK8432000A3 (en) | 2000-12-11 |
Family
ID=20409281
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK843-2000A SK8432000A3 (en) | 1997-12-05 | 1998-12-01 | Adamantane derivatives |
Country Status (25)
Country | Link |
---|---|
US (3) | US6201024B1 (fr) |
EP (1) | EP1036059B1 (fr) |
JP (1) | JP2001525392A (fr) |
KR (1) | KR20010032814A (fr) |
CN (1) | CN1284057A (fr) |
AT (1) | ATE224360T1 (fr) |
AU (1) | AU744280B2 (fr) |
BR (1) | BR9813390A (fr) |
CA (1) | CA2312420A1 (fr) |
DE (1) | DE69808130T2 (fr) |
DK (1) | DK1036059T3 (fr) |
EE (1) | EE200000378A (fr) |
ES (1) | ES2184352T3 (fr) |
HU (1) | HUP0004434A3 (fr) |
ID (1) | ID28003A (fr) |
IL (1) | IL136369A0 (fr) |
NO (1) | NO20002786L (fr) |
NZ (1) | NZ504447A (fr) |
PL (1) | PL340906A1 (fr) |
PT (1) | PT1036059E (fr) |
RU (1) | RU2214997C2 (fr) |
SE (1) | SE9704544D0 (fr) |
SK (1) | SK8432000A3 (fr) |
TR (1) | TR200001605T2 (fr) |
WO (1) | WO1999029661A1 (fr) |
Families Citing this family (72)
Publication number | Priority date | Publication date | Assignee | Title |
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AU3742100A (en) * | 1999-03-16 | 2000-10-04 | Glaxo Group Limited | Nuclear receptor arylating compounds |
BR0009651A (pt) * | 1999-04-09 | 2002-01-08 | Astrazeneca Ab | Composto, processo para a preparação de um composto, composição farmacêutica, uso de um composto, e, método para tratar artrite reumatóide e uma doença obstrutiva das vias aéreas |
SE9904505D0 (sv) * | 1999-12-09 | 1999-12-09 | Astra Pharma Prod | Novel compounds |
TWI258462B (en) | 1999-12-17 | 2006-07-21 | Astrazeneca Ab | Adamantane derivative compounds, process for preparing the same and pharmaceutical composition comprising the same |
SE9904738D0 (sv) * | 1999-12-22 | 1999-12-22 | Astra Pharma Prod | Novel compounds |
NZ522074A (en) | 2000-05-31 | 2004-06-25 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
GB0013737D0 (en) * | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
JP2002330787A (ja) * | 2000-10-21 | 2002-11-19 | Astrazeneca Ab | 化学物質 |
US7795468B2 (en) * | 2001-01-19 | 2010-09-14 | Chevron U.S.A. Inc. | Functionalized higher diamondoids |
EP2335700A1 (fr) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Inhibiteurs de la polymerase du virus hepatitis C avec une structure heterobicylic |
SE524952C2 (sv) * | 2001-09-02 | 2004-10-26 | Sandvik Ab | Duplex rostfri stållegering |
SE524951C2 (sv) * | 2001-09-02 | 2004-10-26 | Sandvik Ab | Användning av en duplex rostfri stållegering |
PA8557501A1 (es) | 2001-11-12 | 2003-06-30 | Pfizer Prod Inc | Benzamida, heteroarilamida y amidas inversas |
WO2003042190A1 (fr) | 2001-11-12 | 2003-05-22 | Pfizer Products Inc. | Derives de n-adamantylalkyle benzamide en tant qu'antagonistes du recepteur p2x7 |
SE0103836D0 (sv) * | 2001-11-16 | 2001-11-16 | Astrazeneca Ab | Novel compounds |
SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
AU2003214462A1 (en) | 2002-04-03 | 2003-10-13 | Astrazeneca Ab | Indole derivatives having anti-angiogenetic activity |
US7582309B2 (en) * | 2002-11-15 | 2009-09-01 | Etex Corporation | Cohesive demineralized bone compositions |
PA8591801A1 (es) | 2002-12-31 | 2004-07-26 | Pfizer Prod Inc | Inhibidores benzamidicos del receptor p2x7. |
US7071223B1 (en) * | 2002-12-31 | 2006-07-04 | Pfizer, Inc. | Benzamide inhibitors of the P2X7 receptor |
SE0300480D0 (sv) * | 2003-02-21 | 2003-02-21 | Astrazeneca Ab | Novel compounds |
DE602004005033T2 (de) * | 2003-05-12 | 2007-08-09 | Pfizer Products Inc., Groton | Benzamidinhibitoren des p2x7-rezeptors |
US20070032465A1 (en) * | 2003-05-29 | 2007-02-08 | Nigel Boughton-Smith | Pharmaceutical composition comprising a p2x7-receptor antagonist and a tumour necrosis factor alpha |
US20070281931A1 (en) * | 2003-05-29 | 2007-12-06 | Nigel Boughton-Smith | Pharmaceutical Composition Containing a P2x7 Receptor Antagonist and Methotrexate |
US20070010497A1 (en) * | 2003-05-29 | 2007-01-11 | Nigel Boughton-Smith | Pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
GB0312609D0 (en) * | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
GB0324498D0 (en) | 2003-07-21 | 2003-11-26 | Aventis Pharma Inc | Heterocyclic compounds as P2X7 ion channel blockers |
SE0302192D0 (sv) * | 2003-08-08 | 2003-08-08 | Astrazeneca Ab | Novel compounds |
SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
DK1718608T3 (da) | 2004-02-20 | 2013-10-14 | Boehringer Ingelheim Int | Virale polymeraseinhibitorer |
EP1768965A1 (fr) * | 2004-06-29 | 2007-04-04 | Pfizer Products Incorporated | Procede de preparation de derives de 5-`4-(2-hydroxy-ethyl)-3,5-dioxo-4,5-dihydro-3h-`1,2,4-triazin-2-yl-benzamide aant une activite inhibant p2x7 par reaction du derive non substitue en position 4 de triazine avec un oxyrane en presence d'un acide de lewis |
RU2006146675A (ru) * | 2004-06-29 | 2008-07-10 | Пфайзер Продактс Инк. (Us) | Способ получения производных 5-[4-(2-гидроксипропил)-3,5-диоксо-4,5-дигидро-3н-[1,2,4] триазин-2-ил] бензамида снятием защиты с промежуточных продуктов, содержащих защищенный гидроксил |
JP2008504363A (ja) * | 2004-06-29 | 2008-02-14 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | P2x7受容体のベンズアミド阻害剤を利用する併用療法 |
SA05260265A (ar) * | 2004-08-30 | 2005-12-03 | استرازينيكا ايه بي | مركبات جديدة |
US20060063834A1 (en) * | 2004-09-09 | 2006-03-23 | Frangioni John V | Substituted adamantanes, and methods of making the same |
SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
US20060235028A1 (en) * | 2005-04-14 | 2006-10-19 | Li James J | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
CA2609969C (fr) * | 2005-06-06 | 2015-10-27 | Merck Sharp & Dohme Limited | Derives de cyclohexanesulfonyle en tant qu'inhibiteurs de glyt1 pour traiter la schizophrenie |
TWI464148B (zh) | 2006-03-16 | 2014-12-11 | Evotec Us Inc | 作為p2x7調節劑之雙環雜芳基化合物與其用途 |
DK2001474T3 (en) | 2006-03-16 | 2016-05-09 | Second Genome Inc | BICYCLOHETEROARYL COMPOUNDS AS P2X7 MODULATORS AND APPLICATIONS THEREOF |
CA2645551C (fr) | 2006-03-16 | 2016-06-28 | Renovis, Inc. | Composes de bicycloheteroaryle en tant que modulateurs de p2x7 et leurs utilisations |
WO2008003697A1 (fr) * | 2006-07-06 | 2008-01-10 | Glaxo Group Limited | N-phenylmethyl -5-oxo-proline-2-amides substitués tenant lieu d'antagonistes du récepteur p2x7 et procédés d'utilisation |
MX2009005478A (es) | 2006-11-27 | 2009-08-12 | Lundbeck & Co As H | Derivados de heteroarilamida. |
EP2124562B1 (fr) | 2007-03-09 | 2016-04-20 | Second Genome, Inc. | Composés de bicyclohétéroaryle utilisés comme modulateurs de p2x7 et leurs utilisations |
JP2010522227A (ja) | 2007-03-22 | 2010-07-01 | アストラゼネカ・アクチエボラーグ | 炎症性疾患の処置のためのキノリン誘導体 |
GB0705882D0 (en) | 2007-03-27 | 2007-05-02 | Glaxo Group Ltd | Novel compounds |
US20100168171A1 (en) * | 2007-03-28 | 2010-07-01 | Paul John Beswick | Piperidinone Carboxamide Derivatives as P2X7 Modulators |
EP2155744A1 (fr) | 2007-04-10 | 2010-02-24 | Lundbeck, H., A/S | Analogues d'heteroaryl-amides utilises en tant qu'antagonistes de p2x7 |
ES2551095T3 (es) | 2007-07-19 | 2015-11-16 | Lundbeck, H., A/S | Amidas heterocíclicas de 5 miembros y compuestos relacionados |
WO2009073300A1 (fr) * | 2007-11-02 | 2009-06-11 | Vertex Pharmaceuticals Incorporated | Dérivés de [1h-pyrazolo[3,4-b]pyridin-4-yl]-phényle ou -pyridin-2-yle en tant qu'inhibiteurs de la protéine kinase c-thêta |
US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
EP2105164B1 (fr) | 2008-03-25 | 2011-01-12 | Affectis Pharmaceuticals AG | Nouveaux antagonistes P2X7R et leur utilisation |
RU2386616C2 (ru) | 2008-04-23 | 2010-04-20 | Общество С Ограниченной Ответственностью "Бинатех" | Производные 5-гидрокси-4-аминометил-1-циклогексил (или циклогептил)-3-алкоксикарбонилиндолов, их фармацевтически приемлемые соли, обладающие противовирусной активностью, и способ их получения |
BRPI0923488A2 (pt) | 2008-12-23 | 2019-09-24 | Hoffmann La Roche | amidas de didropiridona como modulares p2x7 |
CN102264701A (zh) | 2008-12-23 | 2011-11-30 | 霍夫曼-拉罗奇有限公司 | 作为p2x7调节剂的二氢吡啶酮脲 |
CA2745864A1 (fr) | 2008-12-23 | 2010-07-01 | F.Hoffmann-La Roche Ag | Dihydropyridone amides en tant que modulateurs de p2x7 |
EP2243772B1 (fr) | 2009-04-14 | 2012-01-18 | Affectis Pharmaceuticals AG | Nouveaux antagonistes P2X7R et leur utilisation |
EP2322149A1 (fr) | 2009-11-03 | 2011-05-18 | Universidad del Pais Vasco | Procédés et compositions de traitement de l'ischémie |
JP2013526542A (ja) | 2010-05-12 | 2013-06-24 | アッヴィ・インコーポレイテッド | キナーゼのインダゾール阻害薬 |
EP2386541A1 (fr) | 2010-05-14 | 2011-11-16 | Affectis Pharmaceuticals AG | Nouveaux procédés de préparation d'antagonistes de P2X7R |
WO2012110190A1 (fr) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Nouveaux antagonistes p2x7r et leur utilisation |
WO2012163792A1 (fr) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Nouveaux antagonistes de p2x7r et leur utilisation |
WO2012163456A1 (fr) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Nouveaux antagonistes de p2x7r et leur utilisation |
KR101957843B1 (ko) * | 2011-10-06 | 2019-03-14 | (주)아모레퍼시픽 | 신규 아다만탄 유도체 화합물 |
US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
US9775843B2 (en) | 2012-10-11 | 2017-10-03 | Grünenthal GmbH | Treatment and/or prophylaxis of TSPO mediated diseases and/or disorders |
US9718774B2 (en) * | 2012-12-12 | 2017-08-01 | Idorsia Pharmaceuticals Ltd | Indole carboxamide derivatives as P2X7 receptor antagonist |
EP2935211B1 (fr) * | 2012-12-18 | 2016-11-09 | Actelion Pharmaceuticals Ltd. | Dérivés d'indole carboxamide utilisés en tant qu'antagonistes du récepteur p2x7 |
JP6064062B2 (ja) | 2013-03-15 | 2017-01-18 | ファイザー・インク | Ampkを活性化させるインダゾール化合物 |
WO2016032182A1 (fr) * | 2014-08-29 | 2016-03-03 | (주)아모레퍼시픽 | Nouveau composé dérivé d'adamantane |
KR102529578B1 (ko) | 2014-08-29 | 2023-05-09 | (주)아모레퍼시픽 | 신규 아다만탄 유도체 화합물 |
WO2020037350A1 (fr) * | 2018-08-24 | 2020-02-27 | The University Of Sydney | Composés benzamide substitués par adamantanyle et leur utilisation en tant qu'antagonistes du récepteur p2x7 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3464998A (en) | 1968-03-04 | 1969-09-02 | Searle & Co | Adamantyl esters and amides of pyridinecarboxylic acids |
US3732305A (en) * | 1970-03-03 | 1973-05-08 | Us Army | S-substituted thiosulfuric acid derivatives and preparation thereof |
US3789072A (en) | 1970-04-22 | 1974-01-29 | Squibb & Sons Inc | Carboxamides |
CA2015473C (fr) * | 1989-04-28 | 1998-04-14 | Iwao Kinoshita | Derives de triphenylmethane |
CA2091194A1 (fr) * | 1992-04-08 | 1993-10-09 | Richard D. Connell | Derives 2-oxoethyliques utilises comme immunosuppresseurs |
ATE197146T1 (de) | 1993-08-10 | 2000-11-15 | Black James Foundation | Gastrin-und cck-rezeptorligande |
GB9409150D0 (en) | 1994-05-09 | 1994-06-29 | Black James Foundation | Cck and gastrin receptor ligands |
-
1997
- 1997-12-05 SE SE9704544A patent/SE9704544D0/xx unknown
-
1998
- 1998-12-01 JP JP2000524258A patent/JP2001525392A/ja active Pending
- 1998-12-01 EE EEP200000378A patent/EE200000378A/xx unknown
- 1998-12-01 NZ NZ504447A patent/NZ504447A/en unknown
- 1998-12-01 CN CN98813491A patent/CN1284057A/zh active Pending
- 1998-12-01 PL PL98340906A patent/PL340906A1/xx unknown
- 1998-12-01 TR TR2000/01605T patent/TR200001605T2/xx unknown
- 1998-12-01 RU RU2000117574/04A patent/RU2214997C2/ru not_active IP Right Cessation
- 1998-12-01 ID IDW20001019A patent/ID28003A/id unknown
- 1998-12-01 HU HU0004434A patent/HUP0004434A3/hu unknown
- 1998-12-01 KR KR1020007006132A patent/KR20010032814A/ko not_active Application Discontinuation
- 1998-12-01 US US09/230,478 patent/US6201024B1/en not_active Expired - Lifetime
- 1998-12-01 BR BR9813390-0A patent/BR9813390A/pt not_active IP Right Cessation
- 1998-12-01 CA CA002312420A patent/CA2312420A1/fr not_active Abandoned
- 1998-12-01 PT PT98962751T patent/PT1036059E/pt unknown
- 1998-12-01 EP EP98962751A patent/EP1036059B1/fr not_active Expired - Lifetime
- 1998-12-01 AU AU17913/99A patent/AU744280B2/en not_active Ceased
- 1998-12-01 SK SK843-2000A patent/SK8432000A3/sk unknown
- 1998-12-01 ES ES98962751T patent/ES2184352T3/es not_active Expired - Lifetime
- 1998-12-01 DK DK98962751T patent/DK1036059T3/da active
- 1998-12-01 WO PCT/SE1998/002188 patent/WO1999029661A1/fr not_active Application Discontinuation
- 1998-12-01 IL IL13636998A patent/IL136369A0/xx unknown
- 1998-12-01 AT AT98962751T patent/ATE224360T1/de not_active IP Right Cessation
- 1998-12-01 DE DE69808130T patent/DE69808130T2/de not_active Expired - Lifetime
-
2000
- 2000-05-31 NO NO20002786A patent/NO20002786L/no not_active Application Discontinuation
- 2000-12-26 US US09/745,346 patent/US6258838B1/en not_active Expired - Fee Related
- 2000-12-26 US US09/745,740 patent/US6303659B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
KR20010032814A (ko) | 2001-04-25 |
US6201024B1 (en) | 2001-03-13 |
SE9704544D0 (sv) | 1997-12-05 |
EE200000378A (et) | 2001-12-17 |
HUP0004434A2 (hu) | 2001-05-28 |
US20010003121A1 (en) | 2001-06-07 |
US6258838B1 (en) | 2001-07-10 |
JP2001525392A (ja) | 2001-12-11 |
RU2214997C2 (ru) | 2003-10-27 |
PL340906A1 (en) | 2001-03-12 |
IL136369A0 (en) | 2001-06-14 |
US6303659B2 (en) | 2001-10-16 |
DK1036059T3 (da) | 2002-12-02 |
CA2312420A1 (fr) | 1999-06-17 |
PT1036059E (pt) | 2003-02-28 |
NO20002786L (no) | 2000-07-31 |
NO20002786D0 (no) | 2000-05-31 |
BR9813390A (pt) | 2000-10-03 |
DE69808130D1 (de) | 2002-10-24 |
AU744280B2 (en) | 2002-02-21 |
TR200001605T2 (tr) | 2000-10-23 |
EP1036059A1 (fr) | 2000-09-20 |
DE69808130T2 (de) | 2003-05-28 |
WO1999029661A1 (fr) | 1999-06-17 |
EP1036059B1 (fr) | 2002-09-18 |
CN1284057A (zh) | 2001-02-14 |
ES2184352T3 (es) | 2003-04-01 |
HUP0004434A3 (en) | 2002-12-28 |
ID28003A (id) | 2001-05-03 |
ATE224360T1 (de) | 2002-10-15 |
AU1791399A (en) | 1999-06-28 |
NZ504447A (en) | 2002-04-26 |
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