JP2005504747A - 薬物 - Google Patents
薬物 Download PDFInfo
- Publication number
- JP2005504747A JP2005504747A JP2003515497A JP2003515497A JP2005504747A JP 2005504747 A JP2005504747 A JP 2005504747A JP 2003515497 A JP2003515497 A JP 2003515497A JP 2003515497 A JP2003515497 A JP 2003515497A JP 2005504747 A JP2005504747 A JP 2005504747A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydroxy
- alkenyl
- methoxy
- ethyl
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims description 6
- 229940079593 drug Drugs 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 91
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- -1 amino, piperidyl Chemical group 0.000 claims description 275
- 150000001875 compounds Chemical class 0.000 claims description 172
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 75
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 43
- 125000003277 amino group Chemical group 0.000 claims description 43
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 38
- 125000003342 alkenyl group Chemical group 0.000 claims description 38
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 37
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 8
- 150000001540 azides Chemical class 0.000 claims description 8
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 8
- 229910052721 tungsten Inorganic materials 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 238000005984 hydrogenation reaction Methods 0.000 claims description 7
- 125000005647 linker group Chemical group 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 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 4
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- IQIOELVNILZQJR-UHFFFAOYSA-N 4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylic acid Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(C(=O)NC3=CC=NC4=CC=C(N=C43)OC)C(O)=O)=CC=C21 IQIOELVNILZQJR-UHFFFAOYSA-N 0.000 claims description 3
- 239000005973 Carvone Substances 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 125000005951 trifluoromethanesulfonyloxy 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
- NKUGCHGBXABNQR-UHFFFAOYSA-N 1-[2-(1,3-benzodioxol-5-yl)ethyl]-n-(6-methoxy-1,5-naphthyridin-4-yl)-4-methylpiperidine-4-carboxamide Chemical compound C1=C2OCOC2=CC(CCN2CCC(CC2)(C)C(=O)NC2=CC=NC3=CC=C(N=C32)OC)=C1 NKUGCHGBXABNQR-UHFFFAOYSA-N 0.000 claims description 2
- BNGJCINCSDUEAL-UHFFFAOYSA-N 1-[2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)ethyl]-n-(8-fluoro-6-methoxyquinolin-4-yl)-4-hydroxypiperidine-4-carboxamide;hydrochloride Chemical compound Cl.O1CCOC(C=N2)=C1C=C2CCN(CC1)CCC1(O)C(=O)NC1=CC=NC2=C(F)C=C(OC)C=C21 BNGJCINCSDUEAL-UHFFFAOYSA-N 0.000 claims description 2
- LMQHDESYTYKPGK-IBGZPJMESA-N 4-hydroxy-1-[(2r)-2-hydroxy-2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]-n-(6-methoxy-1,5-naphthyridin-4-yl)piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC([C@@H](O)CN3CCC(CC3)(O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 LMQHDESYTYKPGK-IBGZPJMESA-N 0.000 claims description 2
- BMQOZNLUBCOQBR-UHFFFAOYSA-N 4-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 BMQOZNLUBCOQBR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- XZOFUFUOKSMJHL-UHFFFAOYSA-N 6-[2-[4-fluoro-4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-1-yl]ethyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(F)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 XZOFUFUOKSMJHL-UHFFFAOYSA-N 0.000 claims description 2
- DYJVGEYZDNXUTF-UHFFFAOYSA-N 6-[2-[4-hydroxy-4-[2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-1-yl]ethyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(O)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 DYJVGEYZDNXUTF-UHFFFAOYSA-N 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
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 150000003950 cyclic amides Chemical class 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 229910005965 SO 2 Inorganic materials 0.000 claims 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 3
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims 2
- XVSNWPMYYVNDKC-FZYLFJGDSA-N (2R)-2-methoxy-N-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(3-oxo-4H-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound COC=1N=C2C(=CC=NC2=CC=1)NC(=O)C1C[C@H](N(CC1)CCC=1C=CC2=C(NC(CS2)=O)C=1)OC XVSNWPMYYVNDKC-FZYLFJGDSA-N 0.000 claims 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- QRZHDCJDCYMKAK-UHFFFAOYSA-N 1-[2-(1,3-benzodioxol-5-yl)ethyl]-4-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)piperidine-4-carboxamide Chemical compound C1=C2OCOC2=CC(CCN2CCC(CC2)(O)C(=O)NC2=CC=NC3=CC=C(N=C32)OC)=C1 QRZHDCJDCYMKAK-UHFFFAOYSA-N 0.000 claims 1
- PXPHCHQEAHKWPI-UHFFFAOYSA-N 1-[2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)ethyl]-4-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)piperidine-4-carboxamide Chemical compound O1CCOC(C=N2)=C1C=C2CCN(CC1)CCC1(O)C(=O)NC1=CC=NC2=CC=C(OC)N=C21 PXPHCHQEAHKWPI-UHFFFAOYSA-N 0.000 claims 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 claims 1
- OARVAZMJJMPTEM-UHFFFAOYSA-N 4-(hydroxymethyl)-n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(CO)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 OARVAZMJJMPTEM-UHFFFAOYSA-N 0.000 claims 1
- SKJILIRDRXLNKR-UHFFFAOYSA-N 4-amino-n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(N)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 SKJILIRDRXLNKR-UHFFFAOYSA-N 0.000 claims 1
- PBIHPDRFBYEZGZ-UHFFFAOYSA-N 4-cyano-n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(C(=O)NC3=CC=NC4=CC=C(N=C43)OC)C#N)=CC=C21 PBIHPDRFBYEZGZ-UHFFFAOYSA-N 0.000 claims 1
- FIMGZXMBDCMXPT-UHFFFAOYSA-N 4-hydroxy-n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-oxo-2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(C(=O)CN3CCC(CC3)(O)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 FIMGZXMBDCMXPT-UHFFFAOYSA-N 0.000 claims 1
- 125000003302 alkenyloxy group Chemical group 0.000 claims 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- LDUXXRURVFSEKO-UHFFFAOYSA-N n-(6-methoxy-1,5-naphthyridin-4-yl)-1-[2-(6-oxo-5h-pyridazino[3,4-b][1,4]thiazin-3-yl)ethyl]-4-(trifluoromethyl)piperidine-4-carboxamide Chemical compound N1C(=O)CSC(N=N2)=C1C=C2CCN(CC1)CCC1(C(F)(F)F)C(=O)NC1=CC=NC2=CC=C(OC)N=C21 LDUXXRURVFSEKO-UHFFFAOYSA-N 0.000 claims 1
- VPBDSFQBBRTQBO-UHFFFAOYSA-N n-(6-methoxy-1,5-naphthyridin-4-yl)-4-methyl-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxamide Chemical compound S1CC(=O)NC2=CC(CCN3CCC(CC3)(C)C(=O)NC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 VPBDSFQBBRTQBO-UHFFFAOYSA-N 0.000 claims 1
- 150000003053 piperidines Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 318
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 240
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 202
- 239000000203 mixture Substances 0.000 description 120
- 150000002500 ions Chemical class 0.000 description 114
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 109
- 238000006243 chemical reaction Methods 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 239000000377 silicon dioxide Substances 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 45
- 150000002148 esters Chemical class 0.000 description 43
- 150000001412 amines Chemical class 0.000 description 42
- 235000019441 ethanol Nutrition 0.000 description 41
- 239000012458 free base Substances 0.000 description 38
- 238000004587 chromatography analysis Methods 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 239000000284 extract Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 32
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 31
- 239000000047 product Substances 0.000 description 29
- 150000001408 amides Chemical class 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
- 150000001299 aldehydes Chemical class 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 22
- 239000002585 base Substances 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000012279 sodium borohydride Substances 0.000 description 18
- 229910000033 sodium borohydride Inorganic materials 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 150000003839 salts Chemical class 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- 238000003795 desorption Methods 0.000 description 14
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 13
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 230000007062 hydrolysis Effects 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 10
- 238000007796 conventional method Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 235000006408 oxalic acid Nutrition 0.000 description 10
- 150000002924 oxiranes Chemical class 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- UYCAUPASBSROMS-AWQJXPNKSA-M sodium;2,2,2-trifluoroacetate Chemical compound [Na+].[O-][13C](=O)[13C](F)(F)F UYCAUPASBSROMS-AWQJXPNKSA-M 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
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- 150000003461 sulfonyl halides Chemical class 0.000 description 1
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- 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
- ZOWHATOOYJUFDQ-LRHAYUFXSA-N tert-butyl (2R)-2-methoxy-4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]piperidine-1-carboxylate Chemical compound CO[C@@H]1CC(CCN1C(=O)OC(C)(C)C)C(=O)Nc1ccnc2ccc(OC)nc12 ZOWHATOOYJUFDQ-LRHAYUFXSA-N 0.000 description 1
- ADPIEGXXCABJCH-UHFFFAOYSA-N tert-butyl 1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)NCC1 ADPIEGXXCABJCH-UHFFFAOYSA-N 0.000 description 1
- RWSAEABPDVMLJS-UHFFFAOYSA-N tert-butyl 4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]-4-(trifluoromethyl)piperidine-1-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(C(F)(F)F)CCN(C(=O)OC(C)(C)C)CC1 RWSAEABPDVMLJS-UHFFFAOYSA-N 0.000 description 1
- JYJJTYIKMGJMTR-UHFFFAOYSA-N tert-butyl 4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]-4-methylpiperidine-1-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(C)CCN(C(=O)OC(C)(C)C)CC1 JYJJTYIKMGJMTR-UHFFFAOYSA-N 0.000 description 1
- DEDOWMPOPVYWFM-UHFFFAOYSA-N tert-butyl 4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]piperidine-4-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(C(=O)OC(C)(C)C)CCNCC1 DEDOWMPOPVYWFM-UHFFFAOYSA-N 0.000 description 1
- FXAXDNMQCYEZOZ-UHFFFAOYSA-N tert-butyl 4-[(8-fluoro-6-methoxyquinolin-4-yl)carbamoyl]-4-(methoxymethoxy)piperidine-1-carboxylate Chemical compound C=1C=NC2=C(F)C=C(OC)C=C2C=1NC(=O)C1(OCOC)CCN(C(=O)OC(C)(C)C)CC1 FXAXDNMQCYEZOZ-UHFFFAOYSA-N 0.000 description 1
- STULNXOXJZACHB-UHFFFAOYSA-N tert-butyl 4-carbamoyl-4-(trifluoromethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(F)(F)F)(C(N)=O)CC1 STULNXOXJZACHB-UHFFFAOYSA-N 0.000 description 1
- YZXCHVNFNSZTAN-UHFFFAOYSA-N tert-butyl 4-cyano-4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]piperidine-1-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(C#N)CCN(C(=O)OC(C)(C)C)CC1 YZXCHVNFNSZTAN-UHFFFAOYSA-N 0.000 description 1
- YVWDDHLYIXFZPL-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]piperidine-1-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(O)CCN(C(=O)OC(C)(C)C)CC1 YVWDDHLYIXFZPL-UHFFFAOYSA-N 0.000 description 1
- YOWRRGPVEHZWLE-UHFFFAOYSA-N tert-butyl 4-methoxy-4-[(6-methoxy-1,5-naphthyridin-4-yl)carbamoyl]piperidine-1-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1NC(=O)C1(OC)CCN(C(=O)OC(C)(C)C)CC1 YOWRRGPVEHZWLE-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- FQZLNQAUUMSUHT-UHFFFAOYSA-N tert-butyl n,n-bis(2-chloroethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCl)CCCl FQZLNQAUUMSUHT-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- XJPANWOKBWZVHC-UHFFFAOYSA-N tetrazol-2-amine Chemical compound NN1N=CN=N1 XJPANWOKBWZVHC-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 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
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 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
- 150000005691 triesters Chemical class 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
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-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
- XZZNDPSIHUTMOC-UHFFFAOYSA-N triphenyl phosphate Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)(=O)OC1=CC=CC=C1 XZZNDPSIHUTMOC-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- ADZJWYULTMTLQZ-UHFFFAOYSA-N tritylphosphane;hydrobromide Chemical compound [Br-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 ADZJWYULTMTLQZ-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- PGOLTJPQCISRTO-UHFFFAOYSA-N vinyllithium Chemical compound [Li]C=C PGOLTJPQCISRTO-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—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)
- 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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
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| GBGB0118238.5A GB0118238D0 (en) | 2001-07-26 | 2001-07-26 | Medicaments |
| PCT/EP2002/008319 WO2003010138A2 (en) | 2001-07-26 | 2002-07-25 | Piperidine derivatives as antibacterial agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005504747A true JP2005504747A (ja) | 2005-02-17 |
| JP2005504747A5 JP2005504747A5 (cg-RX-API-DMAC7.html) | 2006-01-05 |
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| JP2003515497A Pending JP2005504747A (ja) | 2001-07-26 | 2002-07-25 | 薬物 |
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| EP (1) | EP1419155B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2005504747A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE344799T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2002328972A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE60215951T2 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2274999T3 (cg-RX-API-DMAC7.html) |
| GB (1) | GB0118238D0 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2003010138A2 (cg-RX-API-DMAC7.html) |
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| JP2014508116A (ja) * | 2010-12-14 | 2014-04-03 | メルク・シャープ・アンド・ドーム・コーポレーション | 大環状ラクタムの調製のための方法および中間体 |
| JP2015514795A (ja) * | 2012-04-27 | 2015-05-21 | ヤンセン ファーマシューティカ エヌ．ベー． | 抗菌性キノリン誘導体 |
| JP2015518003A (ja) * | 2012-04-27 | 2015-06-25 | ヤンセン ファーマシューティカ エヌ．ベー． | 抗菌性キノリン誘導体 |
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| US6803369B1 (en) | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| EP1320529B1 (en) * | 2000-09-21 | 2006-05-24 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
| GB0031086D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031088D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) * | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
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| US7109213B2 (en) * | 2002-01-29 | 2006-09-19 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| US7312212B2 (en) | 2002-01-29 | 2007-12-25 | Glaxo Group Limited | Aminopiperidine derivatives |
| TW200406413A (en) | 2002-06-26 | 2004-05-01 | Glaxo Group Ltd | Compounds |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| ATE463494T1 (de) | 2002-10-10 | 2010-04-15 | Morphochem Ag Komb Chemie | Neue verbindungen mit antibakterieller aktivität |
| US7618959B2 (en) | 2002-11-05 | 2009-11-17 | Smithklinebeecham Corp | Antibacterial agents |
| AU2003303956A1 (en) | 2002-11-05 | 2004-11-23 | Smithkline Beecham Corporation | Antibacterial agents |
| TW200427688A (en) * | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| CN100413865C (zh) * | 2004-01-08 | 2008-08-27 | 弗·哈夫曼-拉罗切有限公司 | 二氮杂-螺哌啶衍生物 |
| FR2867472B1 (fr) * | 2004-03-12 | 2008-07-18 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leurs procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| EP1768954A4 (en) | 2004-06-24 | 2008-05-28 | Incyte Corp | 2-METHYLPROPANAMIDES AND THEIR USE AS PHARMACEUTICALS |
| WO2006017326A1 (en) | 2004-07-13 | 2006-02-16 | Glaxo Group Limited | Antibacterial agents |
| EP1650186B1 (en) * | 2004-10-22 | 2008-06-04 | Bioprojet | Novel dicarboxylic acid derivatives |
| WO2006081289A2 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
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| EP1846418A4 (en) | 2005-01-25 | 2009-12-23 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
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| AU2007223801A1 (en) * | 2006-03-08 | 2007-09-13 | Amgen Inc. | Quinoline and isoquinoline derivatives as phosphodiesterase 10 inhibitors |
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| EP1992628A1 (en) | 2007-05-18 | 2008-11-19 | Glaxo Group Limited | Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones |
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| NL7908031A (nl) * | 1979-11-01 | 1981-06-01 | Acf Chemiefarma Nv | Nieuwe chinolinederivaten en farmaceutische preparaten die een dergelijke verbinding bevatten, alsmede werk- wijze voor het bereiden van deze verbindingen. |
| EP0541486A1 (de) * | 1991-11-07 | 1993-05-12 | Ciba-Geigy Ag | Polycyclische Konjugate |
| US5977134A (en) * | 1996-12-05 | 1999-11-02 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| GB9822450D0 (en) * | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| GB9822440D0 (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 |
| 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 |
| US6403610B1 (en) * | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| US6803369B1 (en) * | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| CN1452619A (zh) * | 2000-07-26 | 2003-10-29 | 史密斯克莱·比奇曼公司 | 具有抗细菌活性的氨基哌啶喹啉和它们的氮杂等排的类似物 |
| EP1320529B1 (en) * | 2000-09-21 | 2006-05-24 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
| US6603005B2 (en) * | 2000-11-15 | 2003-08-05 | Aventis Pharma S.A. | Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them |
| FR2816618B1 (fr) * | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
| GB0031086D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031088D0 (en) * | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) * | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| US6602884B2 (en) * | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| 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 |
| US7109213B2 (en) * | 2002-01-29 | 2006-09-19 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| US7312212B2 (en) * | 2002-01-29 | 2007-12-25 | Glaxo Group Limited | Aminopiperidine derivatives |
| GB0217294D0 (en) * | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
-
2001
- 2001-07-26 GB GBGB0118238.5A patent/GB0118238D0/en not_active Ceased
-
2002
- 2002-07-25 US US10/484,563 patent/US20040198756A1/en not_active Abandoned
- 2002-07-25 WO PCT/EP2002/008319 patent/WO2003010138A2/en not_active Ceased
- 2002-07-25 DE DE60215951T patent/DE60215951T2/de not_active Expired - Fee Related
- 2002-07-25 AU AU2002328972A patent/AU2002328972A1/en not_active Abandoned
- 2002-07-25 ES ES02764786T patent/ES2274999T3/es not_active Expired - Lifetime
- 2002-07-25 JP JP2003515497A patent/JP2005504747A/ja active Pending
- 2002-07-25 EP EP02764786A patent/EP1419155B1/en not_active Expired - Lifetime
- 2002-07-25 AT AT02764786T patent/ATE344799T1/de not_active IP Right Cessation
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011148962A1 (ja) * | 2010-05-25 | 2011-12-01 | 大正製薬株式会社 | 新規な複素環化合物又はその塩 |
| JPWO2011148962A1 (ja) * | 2010-05-25 | 2013-07-25 | 大正製薬株式会社 | 新規な複素環化合物又はその塩 |
| JP2014508116A (ja) * | 2010-12-14 | 2014-04-03 | メルク・シャープ・アンド・ドーム・コーポレーション | 大環状ラクタムの調製のための方法および中間体 |
| JP2015514795A (ja) * | 2012-04-27 | 2015-05-21 | ヤンセン ファーマシューティカ エヌ．ベー． | 抗菌性キノリン誘導体 |
| JP2015518003A (ja) * | 2012-04-27 | 2015-06-25 | ヤンセン ファーマシューティカ エヌ．ベー． | 抗菌性キノリン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE344799T1 (de) | 2006-11-15 |
| AU2002328972A1 (en) | 2003-02-17 |
| EP1419155B1 (en) | 2006-11-08 |
| DE60215951D1 (de) | 2006-12-21 |
| WO2003010138A3 (en) | 2003-12-04 |
| WO2003010138A2 (en) | 2003-02-06 |
| DE60215951T2 (de) | 2007-04-26 |
| US20040198756A1 (en) | 2004-10-07 |
| ES2274999T3 (es) | 2007-06-01 |
| EP1419155A2 (en) | 2004-05-19 |
| GB0118238D0 (en) | 2001-09-19 |
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