JP4508650B2 - アミノピペリジン化合物、当該化合物の製法および当該化合物を含有する医薬組成物 - Google Patents
アミノピペリジン化合物、当該化合物の製法および当該化合物を含有する医薬組成物 Download PDFInfo
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- JP4508650B2 JP4508650B2 JP2003564054A JP2003564054A JP4508650B2 JP 4508650 B2 JP4508650 B2 JP 4508650B2 JP 2003564054 A JP2003564054 A JP 2003564054A JP 2003564054 A JP2003564054 A JP 2003564054A JP 4508650 B2 JP4508650 B2 JP 4508650B2
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- -1 Aminopiperidine compound Chemical class 0.000 title claims description 152
- 150000001875 compounds Chemical class 0.000 title claims description 102
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 238000000034 method Methods 0.000 title description 83
- 230000008569 process Effects 0.000 title description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910005965 SO 2 Inorganic materials 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- QBGDAPRNYOMPRF-CBQOVEMMSA-N (1r)-2-[(3r,4s)-3-fluoro-4-(thiadiazolo[5,4-b]pyridin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound N1=C2SN=NC2=CC(CN[C@H]2CCN(C[C@H]2F)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 QBGDAPRNYOMPRF-CBQOVEMMSA-N 0.000 claims description 2
- QBGDAPRNYOMPRF-DWLFOUALSA-N (1r)-2-[(3s,4r)-3-fluoro-4-(thiadiazolo[5,4-b]pyridin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound N1=C2SN=NC2=CC(CN[C@@H]2CCN(C[C@@H]2F)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 QBGDAPRNYOMPRF-DWLFOUALSA-N 0.000 claims description 2
- JVOLXYGUUVLWQC-WPYKKVEZSA-N (1r)-2-[(3s,4r)-4-(1,2,3-benzothiadiazol-5-ylmethylamino)-3-fluoropiperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C1=C2SN=NC2=CC(CN[C@@H]2CCN(C[C@@H]2F)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 JVOLXYGUUVLWQC-WPYKKVEZSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- 239000000203 mixture Substances 0.000 description 50
- 150000001412 amines Chemical class 0.000 description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 34
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
- 235000019441 ethanol Nutrition 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002253 acid Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 125000003118 aryl group Chemical group 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 125000003277 amino group Chemical group 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 229910052763 palladium Inorganic materials 0.000 description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 15
- 125000005843 halogen group Chemical group 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 150000001299 aldehydes Chemical class 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 12
- 125000004414 alkyl thio group Chemical group 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 11
- 229910052760 oxygen Inorganic materials 0.000 description 11
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 10
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 10
- 125000005137 alkenylsulfonyl group Chemical group 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 229910052736 halogen Inorganic materials 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 10
- 241000283690 Bos taurus Species 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 125000004093 cyano group Chemical group *C#N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- 125000004043 oxo group Chemical group O=* 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 239000012279 sodium borohydride Substances 0.000 description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- LGXDAWAHSVHYCG-UHFFFAOYSA-N thiadiazolo[5,4-b]pyridine-6-carbaldehyde Chemical compound O=CC1=CN=C2SN=NC2=C1 LGXDAWAHSVHYCG-UHFFFAOYSA-N 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- XXLFLUJXWKXUGS-UHFFFAOYSA-N 6-methoxyquinoline-4-carboxylic acid Chemical compound N1=CC=C(C(O)=O)C2=CC(OC)=CC=C21 XXLFLUJXWKXUGS-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 description 7
- 150000002118 epoxides Chemical class 0.000 description 7
- 239000012948 isocyanate Substances 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 125000006574 non-aromatic ring group Chemical group 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 229910052721 tungsten Inorganic materials 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 229910052727 yttrium Inorganic materials 0.000 description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000001309 chloro group Chemical group Cl* 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 150000002513 isocyanates Chemical class 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 5
- 150000001540 azides Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 description 4
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- ZQRYPCAUVKVMLZ-SFYZADRCSA-N tert-butyl (3r,4s)-4-amino-3-fluoropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)[C@H](F)C1 ZQRYPCAUVKVMLZ-SFYZADRCSA-N 0.000 description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 3
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 description 3
- VFUFXHFSNCESKR-VIFPVBQESA-N 2-methoxy-8-[(2r)-oxiran-2-yl]-1,5-naphthyridine Chemical compound C12=NC(OC)=CC=C2N=CC=C1[C@@H]1CO1 VFUFXHFSNCESKR-VIFPVBQESA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 125000006414 CCl Chemical group ClC* 0.000 description 3
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical class NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 3
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- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0202025A GB0202025D0 (en) | 2002-01-29 | 2002-01-29 | Compounds |
| GB0229819A GB0229819D0 (en) | 2002-12-20 | 2002-12-20 | Compounds |
| PCT/EP2003/000824 WO2003064431A2 (en) | 2002-01-29 | 2003-01-27 | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005519922A JP2005519922A (ja) | 2005-07-07 |
| JP2005519922A5 JP2005519922A5 (enExample) | 2006-01-12 |
| JP4508650B2 true JP4508650B2 (ja) | 2010-07-21 |
Family
ID=27665356
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003564054A Expired - Fee Related JP4508650B2 (ja) | 2002-01-29 | 2003-01-27 | アミノピペリジン化合物、当該化合物の製法および当該化合物を含有する医薬組成物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7109213B2 (enExample) |
| EP (1) | EP1470131A2 (enExample) |
| JP (1) | JP4508650B2 (enExample) |
| AU (1) | AU2003239302A1 (enExample) |
| WO (1) | WO2003064431A2 (enExample) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6803369B1 (en) | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) * | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0118238D0 (en) * | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
| WO2003064421A1 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine derivatives |
| AR040335A1 (es) * | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| AU2003291227A1 (en) | 2002-11-05 | 2004-06-07 | Smithkline Beecham Corporation | Antibacterial agents |
| WO2004050036A2 (en) * | 2002-12-04 | 2004-06-17 | Glaxo Group Limited | Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents |
| TW200427688A (en) * | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| ES2436888T3 (es) | 2003-09-26 | 2014-01-07 | Exelixis, Inc | Moduladores c-Met y métodos de uso |
| US7691850B2 (en) * | 2004-06-15 | 2010-04-06 | Glaxo Group Limited | Antibacterial agents |
| EP1773831A1 (en) * | 2004-07-08 | 2007-04-18 | Glaxo Group Limited | Antibacterial agents |
| DE602005024151D1 (de) | 2004-08-02 | 2010-11-25 | Glaxo Group Ltd | Antibakterielle mittel |
| WO2006081182A2 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| WO2006081178A2 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| WO2006081179A1 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| US7605169B2 (en) | 2005-01-25 | 2009-10-20 | Glaxo Group Limited | Antibacterial agents |
| WO2006081289A2 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| EP1863483A4 (en) | 2005-03-31 | 2010-03-31 | Janssen Pharmaceutica Nv | Bicyclic pyrazole compounds as anti-bacteriostatic agents |
| MY150958A (en) | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
| EP1954697B1 (en) * | 2005-10-21 | 2010-02-24 | Glaxo Group Limited | Peri condensed tricyclic compounds useful as antibacterial agents |
| EP1790342A1 (de) | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
| US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
| US20070185153A1 (en) | 2005-12-22 | 2007-08-09 | Nathalie Cailleau | Compounds |
| JP2009524643A (ja) | 2006-01-26 | 2009-07-02 | アクテリオン ファーマシューティカルズ リミテッド | テトラヒドロピラン抗生物質 |
| EP1991531A1 (en) * | 2006-02-28 | 2008-11-19 | Amgen Inc. | Cinnoline and quinoxaline derivates as phosphodiesterase 10 inhibitors |
| MX2008011220A (es) * | 2006-03-07 | 2008-09-11 | Array Biopharma Inc | Compuestos de pirazol heterobiciclicos y metodos de uso. |
| EP2001887B1 (en) | 2006-04-06 | 2010-09-15 | Glaxo Group Limited | Pyrrolo-quinoxalinone derivatives as antibacterials |
| EP2007377A4 (en) | 2006-04-06 | 2011-08-17 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| GB0608263D0 (en) * | 2006-04-26 | 2006-06-07 | Glaxo Group Ltd | Compounds |
| GB0613208D0 (en) | 2006-07-03 | 2006-08-09 | Glaxo Group Ltd | Compounds |
| EP1992628A1 (en) | 2007-05-18 | 2008-11-19 | Glaxo Group Limited | Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones |
| WO2008071964A1 (en) * | 2006-12-15 | 2008-06-19 | Astrazeneca Ab | Naphthyridine bactericides |
| GB0705672D0 (en) * | 2007-03-23 | 2007-05-02 | Glaxo Group Ltd | Compounds |
| GB0707708D0 (en) * | 2007-04-20 | 2007-05-30 | Glaxo Group Ltd | Compounds |
| GB0707706D0 (en) * | 2007-04-20 | 2007-05-30 | Glaxo Group Ltd | Compounds |
| CA2684659C (en) * | 2007-04-20 | 2015-11-24 | Glaxo Group Limited | Tricyclic nitrogen containing compounds as antibacterial agents |
| EP2005995A1 (en) * | 2007-06-22 | 2008-12-24 | Glaxo Group Limited | Heterocyclic compounds for the treatment of tuberculosis |
| EP2080761A1 (en) | 2008-01-18 | 2009-07-22 | Glaxo Group Limited | Compounds |
| WO2010043714A1 (en) | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
| JP5653935B2 (ja) | 2009-01-15 | 2015-01-14 | グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ | 抗菌薬として有用なナフチリジン―２（１ｈ）−オン化合物 |
| CA2995880C (en) | 2009-01-16 | 2021-01-05 | Exelixis, Inc. | Processes for preparing n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| WO2016027249A1 (en) | 2014-08-22 | 2016-02-25 | Glaxosmithkline Intellectual Property Development Limited | Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection |
| TW201722965A (zh) | 2015-08-16 | 2017-07-01 | 葛蘭素史密斯克藍智慧財產發展有限公司 | 用於抗菌應用之化合物 |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1345872A (en) | 1970-09-03 | 1974-02-06 | Wyeth John & Brother Ltd | Amino-and acylamino-pyridine and hydropyridine derivatives |
| GB1537867A (en) | 1977-07-04 | 1979-01-04 | Wyeth John & Brother Ltd | Process for preparing 4-acylamino-piperidine derivatives |
| US4925877A (en) | 1986-02-25 | 1990-05-15 | Zaidanhojin Biseibutsu Kagaku Kenkyukai | Physiologically active erbstatin analogue compounds and compositions |
| DE3874257T2 (de) | 1987-03-11 | 1993-02-11 | Kanegafuchi Chemical Ind | Hydroxystyren-derivate. |
| ZA899436B (en) | 1988-12-12 | 1990-08-29 | Ciba Geigy | Piperidine derivatives |
| MY110227A (en) * | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
| EP0541486A1 (de) * | 1991-11-07 | 1993-05-12 | Ciba-Geigy Ag | Polycyclische Konjugate |
| ATE208772T1 (de) | 1993-10-01 | 2001-11-15 | Novartis Erfind Verwalt Gmbh | Pharmacologisch wirksame pyridinderivate und verfahren zu deren herstellung |
| JPH07179407A (ja) | 1993-11-12 | 1995-07-18 | Green Cross Corp:The | 新規縮合環系化合物またはその塩、およびその医薬用途 |
| AU711426B2 (en) | 1994-11-14 | 1999-10-14 | Warner-Lambert Company | 6-aryl pyrido(2,3-d)pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| JP3938936B2 (ja) | 1995-04-26 | 2007-06-27 | 協和醗酵工業株式会社 | ラディシコール誘導体 |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| WO1997017957A1 (en) | 1995-11-13 | 1997-05-22 | Smithkline Beecham Corporation | Hemoregulatory compounds |
| US5707990A (en) | 1996-01-30 | 1998-01-13 | Ortho Pharmaceutical Corporation | 2-substituted amino and thio alkyl benzoxazine antimicrobial agents |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| CA2318842A1 (en) * | 1998-01-26 | 1999-07-29 | Julie Dorothy Warrack | Quinoline derivatives as antibacterials |
| GB9822440D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| GB9822450D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| JP2002535323A (ja) * | 1999-01-20 | 2002-10-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | プロテインキナーゼ阻害剤としてのピペリジニルキノリン |
| GB9914486D0 (en) * | 1999-06-21 | 1999-08-18 | Smithkline Beecham Plc | Medicaments |
| GB9917406D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| GB9917408D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| FR2798656B1 (fr) | 1999-09-17 | 2004-12-17 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6403610B1 (en) * | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| US6803369B1 (en) * | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| DE60125373T2 (de) * | 2000-07-26 | 2007-10-18 | Smithkline Beecham P.L.C., Brentford | Aminopiperidin chinoline und ihre azaisosteren analoga mit antibakterieller wirkung |
| EP1719770A3 (en) * | 2000-09-21 | 2008-03-05 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
| FR2816618B1 (fr) | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
| US6603005B2 (en) * | 2000-11-15 | 2003-08-05 | Aventis Pharma S.A. | Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them |
| GB0031088D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031086D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) * | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| FR2822154B1 (fr) | 2001-03-13 | 2005-10-21 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6602884B2 (en) * | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| FR2822971A1 (fr) * | 2001-04-03 | 2002-10-04 | St Microelectronics Sa | Systeme et procede de controle d'acces a des donnees protegees stockees dans une memoire |
| GB0112834D0 (en) * | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US20030203917A1 (en) * | 2001-07-25 | 2003-10-30 | Smithkline Beecham Corporation And Smithkline Beecham P.L.C. | Compounds and methods for the treatment of neoplastic disease |
| GB0118238D0 (en) * | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
| WO2003064421A1 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine derivatives |
| AR040335A1 (es) | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| GB0217294D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| FR2844270B1 (fr) * | 2002-09-11 | 2006-05-19 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur procede et intermediaires de preparation et les compositions qui les contiennent |
| FR2844268B1 (fr) * | 2002-09-11 | 2004-10-22 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leurs procedes et intermediaires de preparation et les compositions qui les contiennent |
| AU2003301414B8 (en) | 2002-10-10 | 2010-06-17 | Morphochem Aktiengesellschaft Fur Kombinatorische Chemie | Novel compounds with antibacterial activity |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| AU2003291227A1 (en) | 2002-11-05 | 2004-06-07 | Smithkline Beecham Corporation | Antibacterial agents |
| WO2004050036A2 (en) | 2002-12-04 | 2004-06-17 | Glaxo Group Limited | Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents |
| TW200427688A (en) | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| US6903214B1 (en) * | 2003-12-11 | 2005-06-07 | Eastman Kodak Company | Synthesis of bis(azinyl)amine-BF2 complex |
-
2003
- 2003-01-27 WO PCT/EP2003/000824 patent/WO2003064431A2/en not_active Ceased
- 2003-01-27 US US10/502,234 patent/US7109213B2/en not_active Expired - Fee Related
- 2003-01-27 AU AU2003239302A patent/AU2003239302A1/en not_active Abandoned
- 2003-01-27 JP JP2003564054A patent/JP4508650B2/ja not_active Expired - Fee Related
- 2003-01-27 EP EP20030734702 patent/EP1470131A2/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US20050085494A1 (en) | 2005-04-21 |
| US7109213B2 (en) | 2006-09-19 |
| JP2005519922A (ja) | 2005-07-07 |
| WO2003064431A3 (en) | 2003-12-18 |
| WO2003064431A2 (en) | 2003-08-07 |
| EP1470131A2 (en) | 2004-10-27 |
| AU2003239302A1 (en) | 2003-09-02 |
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