DE60307860T2 - Aminocyclohexenchinoline und ihre azaisosterischen Analoga mit antibakterieller Wirkung - Google Patents
Aminocyclohexenchinoline und ihre azaisosterischen Analoga mit antibakterieller Wirkung Download PDFInfo
- Publication number
- DE60307860T2 DE60307860T2 DE60307860T DE60307860T DE60307860T2 DE 60307860 T2 DE60307860 T2 DE 60307860T2 DE 60307860 T DE60307860 T DE 60307860T DE 60307860 T DE60307860 T DE 60307860T DE 60307860 T2 DE60307860 T2 DE 60307860T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- alkenyl
- optionally substituted
- hydroxy
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 230000000844 anti-bacterial effect Effects 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 71
- 241000124008 Mammalia Species 0.000 claims abstract description 7
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 6
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 6
- -1 amino, piperidyl Chemical group 0.000 claims description 197
- 125000000217 alkyl group Chemical group 0.000 claims description 147
- 150000001875 compounds Chemical class 0.000 claims description 106
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 230000008569 process Effects 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 33
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 33
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 229910005965 SO 2 Inorganic materials 0.000 claims description 20
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 229910052721 tungsten Inorganic materials 0.000 claims description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 4
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000005647 linker group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- VUHCPMIDSUGHNO-UHFFFAOYSA-N 6-methoxy-1,5-naphthyridin-4-amine Chemical compound N1=CC=C(N)C2=NC(OC)=CC=C21 VUHCPMIDSUGHNO-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 claims description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005361 aryl sulfoxide group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- UYACEJSTFZKGCX-SHACYNPGSA-N (1r,4s)-1-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-[(3-oxo-4h-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohex-2-ene-1-carboxamide Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CC[C@](C=C3)(O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 UYACEJSTFZKGCX-SHACYNPGSA-N 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004442 acylamino group Chemical group 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000596 cyclohexenyl group Chemical class C1(=CCCCC1)* 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 44
- 239000000047 product Substances 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000543 intermediate Substances 0.000 description 34
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 235000019441 ethanol Nutrition 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 150000003254 radicals Chemical class 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 150000002500 ions Chemical class 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 150000002148 esters Chemical class 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 10
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 238000005932 reductive alkylation reaction Methods 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride 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
- PPZNNZQHBXZAPS-UHFFFAOYSA-N (6-methoxy-1,5-naphthyridin-4-yl) trifluoromethanesulfonate Chemical compound N1=CC=C(OS(=O)(=O)C(F)(F)F)C2=NC(OC)=CC=C21 PPZNNZQHBXZAPS-UHFFFAOYSA-N 0.000 description 5
- AGARPHPERRYPRP-UHFFFAOYSA-N 3-bromo-1h-quinolin-2-one Chemical compound C1=CC=C2C=C(Br)C(O)=NC2=C1 AGARPHPERRYPRP-UHFFFAOYSA-N 0.000 description 5
- FHZIDNIJVVSXDL-UHFFFAOYSA-N 4h-pyrido[2,3-e]oxazin-3-one Chemical compound C1=CC=C2ONC(=O)CC2=N1 FHZIDNIJVVSXDL-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- DVVWSQQLTFESAK-UHFFFAOYSA-N 4-bromo-5-fluoro-6-methoxyquinoline Chemical compound N1=CC=C(Br)C2=C(F)C(OC)=CC=C21 DVVWSQQLTFESAK-UHFFFAOYSA-N 0.000 description 4
- SSMACLPPRSQXHH-UHFFFAOYSA-N 6-methoxy-1h-1,5-naphthyridin-4-one Chemical compound N1C=CC(=O)C2=NC(OC)=CC=C21 SSMACLPPRSQXHH-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- SUDWZZCLUSUTBF-UHFFFAOYSA-N 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine-6-carbaldehyde Chemical compound O1CCOC2=NC(C=O)=CC=C21 SUDWZZCLUSUTBF-UHFFFAOYSA-N 0.000 description 3
- OMWBUWDHEZIMGQ-UHFFFAOYSA-N 2,3-dihydro-[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(C=O)N=C2 OMWBUWDHEZIMGQ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- XOXXGNIBXYQQNS-UHFFFAOYSA-N 3-oxo-4h-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde Chemical compound O1CC(=O)NC2=NC(C=O)=CC=C21 XOXXGNIBXYQQNS-UHFFFAOYSA-N 0.000 description 3
- HIWPTYUKGHNQCU-UHFFFAOYSA-N 4-bromo-6-fluoroquinoline Chemical compound N1=CC=C(Br)C2=CC(F)=CC=C21 HIWPTYUKGHNQCU-UHFFFAOYSA-N 0.000 description 3
- HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 description 3
- UUVDJIWRSIJEBS-UHFFFAOYSA-N 6-methoxypyridin-3-amine Chemical compound COC1=CC=C(N)C=N1 UUVDJIWRSIJEBS-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 3
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- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
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- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
- VSGPVHSTVTXREH-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C[C]2C(=O)C=CN=C21 VSGPVHSTVTXREH-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
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- 229940075582 sorbic acid Drugs 0.000 description 1
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- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
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- 150000003440 styrenes Chemical class 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- HSKCWUWGJOAKBS-UHFFFAOYSA-N tert-butyl 4-carbamoyl-3-oxa-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate Chemical compound C1CC2N(C(=O)OC(C)(C)C)OC1(C(N)=O)C=C2 HSKCWUWGJOAKBS-UHFFFAOYSA-N 0.000 description 1
- XTMMLWYEIKLNTB-UHFFFAOYSA-N tert-butyl n-(4-carbamoyl-4-hydroxycyclohex-2-en-1-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)(C(N)=O)C=C1 XTMMLWYEIKLNTB-UHFFFAOYSA-N 0.000 description 1
- OABPVLUPSQVPFN-UHFFFAOYSA-N tert-butyl n-[4-hydroxy-4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]cyclohex-2-en-1-yl]carbamate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(O)CCC(NC(=O)OC(C)(C)C)C=C1 OABPVLUPSQVPFN-UHFFFAOYSA-N 0.000 description 1
- DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000004897 thiazines Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
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- 125000001425 triazolyl group Chemical group 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
- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 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
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-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
- 238000000825 ultraviolet detection 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
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| GB0217294 | 2002-07-25 | ||
| GBGB0217294.8A GB0217294D0 (en) | 2002-07-25 | 2002-07-25 | Medicaments |
| PCT/EP2003/008153 WO2004014361A1 (en) | 2002-07-25 | 2003-07-23 | Aminocyclohexene quinolines and their azaisosteric analogues with antibacterial activity |
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| DE60307860D1 DE60307860D1 (de) | 2006-10-05 |
| DE60307860T2 true DE60307860T2 (de) | 2007-10-11 |
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| AT (1) | ATE336995T1 (enExample) |
| AU (1) | AU2003251474A1 (enExample) |
| DE (1) | DE60307860T2 (enExample) |
| ES (1) | ES2270142T3 (enExample) |
| GB (1) | GB0217294D0 (enExample) |
| WO (1) | WO2004014361A1 (enExample) |
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| GB0118238D0 (en) * | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
| AU2003239302A1 (en) * | 2002-01-29 | 2003-09-02 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| EP1470125A1 (en) | 2002-01-29 | 2004-10-27 | Glaxo Group Limited | Aminopiperidine derivatives |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| 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 |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| ES2350977T3 (es) | 2002-11-05 | 2011-01-28 | Glaxo Group Limited | Agentes antibacterianos. |
| US7491714B2 (en) | 2002-12-04 | 2009-02-17 | Glaxo Group Limited | Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents |
| AR042486A1 (es) * | 2002-12-18 | 2005-06-22 | Glaxo Group Ltd | Compuesto de quinolina y naftiridina halosustituido en la posicion 3, procedimiento para preparar el compuesto, composicion farmaceutica que lo comprende y su uso para preparar dicha composicion . |
| WO2006002047A2 (en) * | 2004-06-15 | 2006-01-05 | Glaxo Group Limited | Antibacterial agents |
| WO2006010040A2 (en) * | 2004-07-09 | 2006-01-26 | Glaxo Group Limited | Antibacterial agents |
| MY150958A (en) | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
| ES2376488T3 (es) | 2006-01-26 | 2012-03-14 | Actelion Pharmaceuticals Ltd. | Antibióticos de tetrahidropirano. |
| EP1991540A1 (en) * | 2006-02-21 | 2008-11-19 | Amgen Inc. | Cinnoline derivatives as phosphodiesterase 10 inhibitors |
| JP2009528365A (ja) * | 2006-02-28 | 2009-08-06 | アムゲン インコーポレイティッド | ホスホジエステラーゼ１０阻害剤としてのシンノリン及びキナゾリン誘導体 |
| MX2008011257A (es) * | 2006-03-08 | 2008-09-25 | Amgen Inc | Derivados de quinolina e isoquinolina como inhibidores de fosfodiesterasa 10. |
| ATE481406T1 (de) | 2006-04-06 | 2010-10-15 | Glaxo Group Ltd | Pyrrolochinoxalinonderivate als antibakterielle mittel |
| JP2009532504A (ja) | 2006-04-06 | 2009-09-10 | グラクソ グループ リミテッド | 抗菌薬 |
| 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 |
| TW200819457A (en) | 2006-08-30 | 2008-05-01 | Actelion Pharmaceuticals Ltd | Spiro antibiotic derivatives |
| PL2137196T3 (pl) * | 2007-04-20 | 2011-03-31 | Glaxo Group Ltd | Tricykliczne związki zawierające azot jako środki przeciwbakteryjne |
| EP2080761A1 (en) | 2008-01-18 | 2009-07-22 | Glaxo Group Limited | Compounds |
| US20110275661A1 (en) | 2008-10-17 | 2011-11-10 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
| EP2379554B1 (en) | 2009-01-15 | 2015-11-11 | Glaxo Group Limited | Naphthyridin-2(1h)-one compounds useful as antibacterials |
| AR089929A1 (es) | 2012-02-10 | 2014-10-01 | Actelion Pharmaceuticals Ltd | Proceso para manufacturar un derivado de naftiridina |
| JP6022691B2 (ja) * | 2012-08-30 | 2016-11-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ジオキシノ−及びオキサジン−［２，３−ｄ］ピリミジンｐｉ３ｋ阻害剤化合物及び使用方法 |
| EA031589B1 (ru) | 2014-08-22 | 2019-01-31 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Трициклические азотсодержащие соединения для лечения инфекции, вызываемой neisseria gonorrhoeae |
| ES2882667T3 (es) | 2015-08-07 | 2021-12-02 | Bayer Cropscience Ag | Derivados heterocíclicos condensados sustituidos por 2-(het)arilo como pesticidas |
| 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 |
| WO2021076886A1 (en) | 2019-10-18 | 2021-04-22 | The Regents Of The University Of California | 3-phenylsulphonyl-quinoline derivatives as agents for treating pathogenic blood vessels disorders |
| CN119161260A (zh) * | 2024-06-26 | 2024-12-20 | 安徽大学 | 一种1-（2-氨基-4-氟-5-甲氧基苯基）-1-丙酮的合成方法 |
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| EP0790981B1 (en) * | 1994-11-10 | 1999-09-08 | Pfizer Inc. | Aryloxycycloalkenyl and aryloxyiminocycloalkenylhydroxyureas as 5-lipoxygenase inhibitors |
| WO1999037635A1 (en) * | 1998-01-26 | 1999-07-29 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
| GB9822450D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| AU2437900A (en) * | 1999-01-20 | 2000-08-07 | Smithkline Beecham Plc | Piperidinylquinolines as protein tyrosine kinase inhibitors |
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| GB9917408D0 (en) * | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| EP1305308B1 (en) * | 2000-07-26 | 2006-12-20 | Smithkline Beecham Plc | Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity |
| FR2816618B1 (fr) * | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
| GB0031088D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) * | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
-
2002
- 2002-07-25 GB GBGB0217294.8A patent/GB0217294D0/en not_active Ceased
-
2003
- 2003-07-23 DE DE60307860T patent/DE60307860T2/de not_active Expired - Lifetime
- 2003-07-23 AU AU2003251474A patent/AU2003251474A1/en not_active Abandoned
- 2003-07-23 US US10/522,058 patent/US20060040925A1/en not_active Abandoned
- 2003-07-23 JP JP2004526773A patent/JP4515260B2/ja not_active Expired - Fee Related
- 2003-07-23 ES ES03784064T patent/ES2270142T3/es not_active Expired - Lifetime
- 2003-07-23 AT AT03784064T patent/ATE336995T1/de not_active IP Right Cessation
- 2003-07-23 EP EP03784064A patent/EP1539133B1/en not_active Expired - Lifetime
- 2003-07-23 WO PCT/EP2003/008153 patent/WO2004014361A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP1539133B1 (en) | 2006-08-23 |
| AU2003251474A1 (en) | 2004-02-25 |
| WO2004014361A9 (en) | 2004-04-08 |
| GB0217294D0 (en) | 2002-09-04 |
| WO2004014361A1 (en) | 2004-02-19 |
| ES2270142T3 (es) | 2007-04-01 |
| AU2003251474A8 (en) | 2004-02-25 |
| JP2005538125A (ja) | 2005-12-15 |
| US20060040925A1 (en) | 2006-02-23 |
| EP1539133A1 (en) | 2005-06-15 |
| JP4515260B2 (ja) | 2010-07-28 |
| ATE336995T1 (de) | 2006-09-15 |
| DE60307860D1 (de) | 2006-10-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8381 | Inventor (new situation) |
Inventor name: DAVIES, DAVID THOMAS, HARLOW, ESSEX, GB Inventor name: ELDER, JOHN STEPHEN, HARLOW, ESSEX, GB Inventor name: FORREST, ANDREW KEITH, HARLOW, ESSEX, GB Inventor name: JARVEST, RICHARD, STEVENAGE, HERTFORDSHIRE, GB Inventor name: PEARSON, NEIL DAVID, HARLOW, ESSEX, GB Inventor name: SHEPPARD, ROBERT JOHN, HARLOW, ESSEX, GB |
|
| 8364 | No opposition during term of opposition |