ES2292716T3 - Quinolinas y derivados nitrogenados de las mismas sustituidos en posicion 4 con un resto que contiene piperidina y su uso como agentes antibacterianos. - Google Patents
Quinolinas y derivados nitrogenados de las mismas sustituidos en posicion 4 con un resto que contiene piperidina y su uso como agentes antibacterianos. Download PDFInfo
- Publication number
- ES2292716T3 ES2292716T3 ES02702296T ES02702296T ES2292716T3 ES 2292716 T3 ES2292716 T3 ES 2292716T3 ES 02702296 T ES02702296 T ES 02702296T ES 02702296 T ES02702296 T ES 02702296T ES 2292716 T3 ES2292716 T3 ES 2292716T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- carbonyl
- hydroxy
- alkenyl
- piperidin
- 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
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 14
- 239000003242 anti bacterial agent Substances 0.000 title description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical class [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 138
- 241000124008 Mammalia Species 0.000 claims abstract description 6
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 3
- -1 amino, piperidyl Chemical group 0.000 claims description 227
- 150000001875 compounds Chemical class 0.000 claims description 209
- 125000000217 alkyl group Chemical group 0.000 claims description 168
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 148
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 124
- 239000002253 acid Substances 0.000 claims description 75
- 125000003342 alkenyl group Chemical group 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- 230000008569 process Effects 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 34
- RNIHVSRNVNYVEP-AWEZNQCLSA-N (1r)-2-(4-aminopiperidin-1-yl)-1-(6-methoxy-1,5-naphthyridin-4-yl)ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(N=C21)OC)N1CCC(N)CC1 RNIHVSRNVNYVEP-AWEZNQCLSA-N 0.000 claims description 31
- UBGKBWLYWATHGF-KRWDZBQOSA-N (1r)-2-(4-aminopiperidin-1-yl)-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N1CCC(N)CC1 UBGKBWLYWATHGF-KRWDZBQOSA-N 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 150000002367 halogens Chemical group 0.000 claims description 24
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 23
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 20
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 19
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 229910052727 yttrium Inorganic materials 0.000 claims description 12
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 11
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 229910052721 tungsten Inorganic materials 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 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
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 8
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
- MHKLNUUEKJHPHP-UHFFFAOYSA-N 2h-1,4-thiazine-6-carboxylic acid Chemical compound OC(=O)C1=CN=CCS1 MHKLNUUEKJHPHP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 6
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- YXGCEBKQJZAGQL-QHCPKHFHSA-N (1r)-2-[4-(1,3-benzodioxol-5-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C1=C2OCOC2=CC(CNC2CCN(CC2)C[C@H](O)C2=CC=NC3=CC=C(C=C32)OC)=C1 YXGCEBKQJZAGQL-QHCPKHFHSA-N 0.000 claims description 3
- WZCJTDWSEDVQNY-DEOSSOPVSA-N (1r)-2-[4-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound O1CCOC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 WZCJTDWSEDVQNY-DEOSSOPVSA-N 0.000 claims description 3
- ZSFFWCNXJDGECL-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 ZSFFWCNXJDGECL-DEOSSOPVSA-N 0.000 claims description 3
- SHVJDPNOVPQBCL-IBGZPJMESA-N 7-bromo-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound N1C(=O)CSC(C=C2Br)=C1N=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 SHVJDPNOVPQBCL-IBGZPJMESA-N 0.000 claims description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- AKVZCTPKTKXUFZ-QHCPKHFHSA-N (1r)-1-(6-methoxyquinolin-4-yl)-2-[4-[(6-nitro-1,3-benzodioxol-5-yl)methylamino]piperidin-1-yl]ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)[N+]([O-])=O)=CC2=C1OCO2 AKVZCTPKTKXUFZ-QHCPKHFHSA-N 0.000 claims description 2
- IQTIWIZDWUXWDH-QHCPKHFHSA-N (1r)-2-[4-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound O1CCOC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 IQTIWIZDWUXWDH-QHCPKHFHSA-N 0.000 claims description 2
- SIUXHCYRZKHSTR-QHCPKHFHSA-N (1r)-2-[4-(3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound S1CCNC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 SIUXHCYRZKHSTR-QHCPKHFHSA-N 0.000 claims description 2
- UQKCHSYMXQWFMW-QHCPKHFHSA-N (1r)-2-[4-[(6-chloro-1,3-benzodioxol-5-yl)methylamino]piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)Cl)=CC2=C1OCO2 UQKCHSYMXQWFMW-QHCPKHFHSA-N 0.000 claims description 2
- JWZQJTGQFHIRFQ-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carboxylic acid Chemical compound O1CCOC2=CC(C(=O)O)=CC=C21 JWZQJTGQFHIRFQ-UHFFFAOYSA-N 0.000 claims description 2
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical group CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 claims description 2
- OPAAZANXDHQVPI-NRFANRHFSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 OPAAZANXDHQVPI-NRFANRHFSA-N 0.000 claims description 2
- OHDMXSQSXYADHZ-NRFANRHFSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 OHDMXSQSXYADHZ-NRFANRHFSA-N 0.000 claims description 2
- UBMVVMILAXGUEA-IBGZPJMESA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 UBMVVMILAXGUEA-IBGZPJMESA-N 0.000 claims description 2
- JBXWVEMLTDXSCR-DEOSSOPVSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-1,4-benzothiazin-3-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 JBXWVEMLTDXSCR-DEOSSOPVSA-N 0.000 claims description 2
- QFSXNHZMFQOXHL-FQEVSTJZSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-1h-pyrido[3,4-b][1,4]thiazin-2-one Chemical compound N1C(=O)CSC(C=N2)=C1C=C2CNC(CC1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 QFSXNHZMFQOXHL-FQEVSTJZSA-N 0.000 claims description 2
- LRSMUZQJQTVFKR-QHCPKHFHSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-1h-pyrido[2,3-b][1,4]thiazin-2-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CN=C21 LRSMUZQJQTVFKR-QHCPKHFHSA-N 0.000 claims description 2
- ORRVDYWUNUCTCY-VWLOTQADSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound S1CCC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 ORRVDYWUNUCTCY-VWLOTQADSA-N 0.000 claims description 2
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
- 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
- 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
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- CIYIYWQDQTXPMR-DEOSSOPVSA-N (1r)-2-[4-(2,3-dihydro-1h-pyrido[2,3-b][1,4]thiazin-7-ylmethylamino)piperidin-1-yl]-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound S1CCNC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CN=C21 CIYIYWQDQTXPMR-DEOSSOPVSA-N 0.000 claims 1
- VPIHWYGVGDBQSG-FQEVSTJZSA-N (1r)-2-[4-(3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazin-6-ylmethylamino)piperidin-1-yl]-1-(6-methoxy-1,5-naphthyridin-4-yl)ethanol Chemical compound O1CCNC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 VPIHWYGVGDBQSG-FQEVSTJZSA-N 0.000 claims 1
- WFPGYFRYIRNCNS-DEOSSOPVSA-N 5-fluoro-6-[[[1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3-methyl-1,3-benzoxazol-2-one Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N(CC1)CCC1NCC(C(=C1)F)=CC2=C1N(C)C(=O)O2 WFPGYFRYIRNCNS-DEOSSOPVSA-N 0.000 claims 1
- CXZFTPXYXXIAKC-NRFANRHFSA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-3,4-dihydro-1h-1,8-naphthyridin-2-one Chemical compound N1C(=O)CCC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CN=C21 CXZFTPXYXXIAKC-NRFANRHFSA-N 0.000 claims 1
- JLAMMHGOVQRIBT-IBGZPJMESA-N 6-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CC=C21 JLAMMHGOVQRIBT-IBGZPJMESA-N 0.000 claims 1
- HIXTTZIJAWUHCI-FQEVSTJZSA-N 7-[[[1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-1h-pyrido[2,3-b][1,4]thiazin-2-one Chemical compound S1CC(=O)NC2=CC(CNC3CCN(CC3)C[C@H](O)C3=CC=NC4=CC=C(N=C43)OC)=CN=C21 HIXTTZIJAWUHCI-FQEVSTJZSA-N 0.000 claims 1
- 125000002071 phenylalkoxy group Chemical group 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 150000003053 piperidines Chemical class 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 235
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 201
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 167
- 239000000243 solution Substances 0.000 description 164
- 239000000203 mixture Substances 0.000 description 118
- 239000007787 solid Substances 0.000 description 116
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
- 238000006243 chemical reaction Methods 0.000 description 102
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 78
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 150000001299 aldehydes Chemical class 0.000 description 53
- 150000002500 ions Chemical class 0.000 description 53
- 235000019441 ethanol Nutrition 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
- 150000001412 amines Chemical class 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 150000002148 esters Chemical class 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
- 239000012458 free base Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- 239000007832 Na2SO4 Substances 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 239000000460 chlorine Substances 0.000 description 23
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- SUJCFHJHXFHMGB-UHFFFAOYSA-N tert-butyl 4-[(7-fluoro-3-oxo-4h-1,4-benzothiazin-6-yl)methylamino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NCC(C(=C1)F)=CC2=C1SCC(=O)N2 SUJCFHJHXFHMGB-UHFFFAOYSA-N 0.000 description 1
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- NZBUCABTIWJWAN-UHFFFAOYSA-N tetrabromomethane;triphenylphosphane Chemical compound BrC(Br)(Br)Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NZBUCABTIWJWAN-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-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
- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 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
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- 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
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- 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
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- 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
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Families Citing this family (96)
| 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 |
| CZ2003243A3 (cs) | 2000-07-26 | 2003-09-17 | Smithkline Beecham P. L. C. | Aminopiperidinové chinoliny a jejich azaisosterické analogy s antibakteriální aktivitou |
| EP1719770A3 (en) * | 2000-09-21 | 2008-03-05 | 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 |
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| EP1470125A1 (en) * | 2002-01-29 | 2004-10-27 | Glaxo Group Limited | Aminopiperidine derivatives |
| WO2003064431A2 (en) * | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| GB0209244D0 (en) * | 2002-04-23 | 2002-06-05 | Glaxo Group Ltd | Compounds |
| TW200406413A (en) | 2002-06-26 | 2004-05-01 | Glaxo Group Ltd | Compounds |
| AR040336A1 (es) * | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de piperidina, uso del mismo para la fabricacion de un medicamento, composicion farmaceutica que lo comprende y procedimiento para preparar dicho compuesto |
| GB0217294D0 (en) * | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| DE10256405A1 (de) * | 2002-12-02 | 2004-06-17 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen, die Topoisomerase IV inhibieren |
| WO2004035569A2 (de) * | 2002-10-10 | 2004-04-29 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Neue verbindungen mit antibakterieller aktivität |
| ATE479683T1 (de) | 2002-11-05 | 2010-09-15 | Glaxo Group Ltd | Antibakterielle mittel |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| AU2003294565A1 (en) | 2002-12-04 | 2004-06-23 | 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 |
| CA2517256C (en) | 2003-02-26 | 2013-04-30 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| TW200507841A (en) * | 2003-03-27 | 2005-03-01 | Glaxo Group Ltd | Antibacterial agents |
| US7160888B2 (en) | 2003-08-22 | 2007-01-09 | Warner Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia |
| WO2005028467A1 (en) * | 2003-09-15 | 2005-03-31 | Anadys Pharmaceuticals, Inc. | Antibacterial 3,5-diaminopiperidine-substitute aromatic and heteroaromatic compounds |
| ES2305844T3 (es) | 2003-09-16 | 2008-11-01 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de tirosina cinasa. |
| GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| EA011277B1 (ru) * | 2004-01-23 | 2009-02-27 | Янссен Фармацевтика Н.В. | Производные хинолина и их применение в качестве ингибиторов микобактерий |
| JP5032851B2 (ja) | 2004-02-03 | 2012-09-26 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
| US7691850B2 (en) | 2004-06-15 | 2010-04-06 | Glaxo Group Limited | Antibacterial agents |
| US20070254872A1 (en) * | 2004-07-08 | 2007-11-01 | Glaxo Group Limited | Antibacterial Agents |
| US7655648B2 (en) | 2004-08-02 | 2010-02-02 | Glaxo Group Limited | Antibacterial agents |
| US20070161627A1 (en) * | 2004-08-09 | 2007-07-12 | Miller William H | Antibacterial agents |
| TW200630337A (en) * | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
| DE102004057595A1 (de) | 2004-11-29 | 2006-06-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substituierte Pteridine zur Behandlung von entzündlichen Erkrankungen |
| DE102004057645A1 (de) * | 2004-11-29 | 2006-06-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substituierte Pteridine zur Behandlung von entzündlichen Erkrankungen |
| DE102004057618A1 (de) * | 2004-11-29 | 2006-06-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substituierte Pteridine zur Behandlung von entzündlichen Erkrankungen |
| DE102004057594A1 (de) * | 2004-11-29 | 2006-06-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substitueirte Pteridine zur Behandlung von entzündlichen Erkrankungen |
| EP1846418A4 (en) * | 2005-01-25 | 2009-12-23 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| JP2008528598A (ja) | 2005-01-25 | 2008-07-31 | グラクソ グループ リミテッド | 抗菌剤 |
| US7648980B2 (en) | 2005-01-25 | 2010-01-19 | Glaxo Group Limited | Antibacterial agents |
| US7709472B2 (en) * | 2005-01-25 | 2010-05-04 | Glaxo Group Limited | Antibacterial agents |
| JP2008528604A (ja) * | 2005-01-25 | 2008-07-31 | グラクソ グループ リミテッド | 抗菌剤 |
| NZ562034A (en) | 2005-03-31 | 2009-10-30 | Janssen Pharmaceutica Nv | Bicyclic pyrazole compounds as antibacterial agents |
| MY150958A (en) | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
| WO2006137485A1 (ja) | 2005-06-24 | 2006-12-28 | Toyama Chemical Co., Ltd. | 新規な含窒素複素環化合物およびその塩 |
| JO2837B1 (en) * | 2005-08-03 | 2014-09-15 | جانسن فارمسيتكا ان في | Quinoline derivatives acting as antibacterial agents |
| JO2952B1 (en) * | 2005-08-03 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Quinoline derivatives acting as antibacterial agents |
| KR20080064173A (ko) * | 2005-10-21 | 2008-07-08 | 글락소 그룹 리미티드 | 항균제로서 유용한 페리 축합 트리시클릭 화합물 |
| DE602006018354D1 (de) * | 2005-12-05 | 2010-12-30 | Pfizer Prod Inc | Verfahren zur behandlung von abnormalem zellwachstum |
| KR101146852B1 (ko) * | 2005-12-05 | 2012-05-16 | 화이자 프로덕츠 인크. | Ｃ?ｍｅｔ／ｈｇｆｒ 억제제의 다형체 |
| ATE465163T1 (de) | 2005-12-22 | 2010-05-15 | Glaxo Group Ltd | Heterocyclische verbindungen, ihre herstellung und ihre verwendung als antibakterielle mittel |
| CA2635126A1 (en) | 2006-01-26 | 2007-08-02 | Actelion Pharmaceuticals Ltd | Tetrahydropyrane antibiotics |
| MX2008010671A (es) * | 2006-02-21 | 2008-10-01 | Amgen Inc | Derivados de cinolina como inhibidores de fosfodiesterasa 10. |
| US20070299067A1 (en) * | 2006-03-08 | 2007-12-27 | Ruiping Liu | Quinoline and isoquinoline derivatives as phosphodiesterase 10 inhibitors |
| DE602007006927D1 (en) | 2006-03-23 | 2010-07-15 | Actelion Pharmaceuticals Ltd | Antibiotische cyclohexyl- oder piperidinylcarboxamid-derivate |
| WO2007110449A1 (en) * | 2006-03-29 | 2007-10-04 | Euro-Celtique S.A. | Benzenesulfonamide compounds and their use |
| WO2007115947A1 (en) | 2006-04-06 | 2007-10-18 | Glaxo Group Limited | Pyrrolo-quinoxalinone derivatives as antibacterials |
| EP2007377A4 (en) | 2006-04-06 | 2011-08-17 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| TW200815353A (en) * | 2006-04-13 | 2008-04-01 | Euro Celtique Sa | Benzenesulfonamide compounds and their use |
| US8937181B2 (en) * | 2006-04-13 | 2015-01-20 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| GB0608263D0 (en) | 2006-04-26 | 2006-06-07 | Glaxo Group Ltd | Compounds |
| CN101454319B (zh) | 2006-05-26 | 2012-06-27 | 富山化学工业株式会社 | 新杂环化合物或其盐及其中间体 |
| 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 |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| WO2008071964A1 (en) * | 2006-12-15 | 2008-06-19 | Astrazeneca Ab | Naphthyridine bactericides |
| EP2118075A1 (de) | 2007-02-06 | 2009-11-18 | Boehringer Ingelheim International GmbH | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US8399486B2 (en) * | 2007-04-09 | 2013-03-19 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use thereof |
| EA015821B1 (ru) * | 2007-04-20 | 2011-12-30 | Глэксо Груп Лимитед | Трициклические азотсодержащие соединения в качестве антибактериальных агентов |
| US8765736B2 (en) * | 2007-09-28 | 2014-07-01 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| CN101874032B (zh) | 2007-11-26 | 2013-02-06 | 富山化学工业株式会社 | 二氮杂萘衍生物一水合物及其制备方法 |
| GB0800367D0 (en) * | 2008-01-09 | 2008-02-20 | Glaxo Group Ltd | Compounds |
| EP2080761A1 (en) | 2008-01-18 | 2009-07-22 | Glaxo Group Limited | Compounds |
| CA2711582A1 (en) | 2008-02-07 | 2009-08-13 | Boehringer Ingelheim International Gmbh | Spirocyclic heterocycles, formulations containing said compounds, use thereof and processes for the preparation thereof |
| RU2501799C2 (ru) | 2008-02-22 | 2013-12-20 | Актелион Фармасьютикалз Лтд | Поизводные оксазолидинона |
| EP2276766A1 (en) | 2008-04-15 | 2011-01-26 | Actelion Pharmaceuticals Ltd. | Tricyclic antibiotics |
| EP2303276B1 (en) | 2008-05-13 | 2013-11-13 | AstraZeneca AB | Fumarate salt of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(n-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline |
| MX2010012855A (es) | 2008-06-03 | 2010-12-21 | Actelion Pharmaceuticals Ltd | Derivados de [4-(1-amino-etil)-ciclohexil]-metil-amina y [6-(1-amino-etil)-tetrahidro-piran-3-il]-metil-amina como antibacterianos. |
| CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| WO2010043714A1 (en) | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
| CN102232078B (zh) | 2008-12-12 | 2014-07-16 | 埃科特莱茵药品有限公司 | 5-氨基-2-(1-羟基-乙基)-四氢吡喃衍生物 |
| ES2561631T3 (es) | 2009-01-15 | 2016-02-29 | Glaxo Group Limited | Compuestos de naftiridin-2(1H)-ona útiles como agentes antibacterianos |
| EP2332939A1 (en) | 2009-11-26 | 2011-06-15 | Æterna Zentaris GmbH | Novel Naphthyridine derivatives and the use thereof as kinase inhibitors |
| CA2854266A1 (en) | 2011-11-30 | 2013-06-06 | Actelion Pharmaceuticals Ltd | 3,7-disubstituted octahydro-2h-pyrido[4,3-e][1,3]oxazin-2-one antibiotics |
| AR089929A1 (es) | 2012-02-10 | 2014-10-01 | Actelion Pharmaceuticals Ltd | Proceso para manufacturar un derivado de naftiridina |
| WO2014057415A2 (en) * | 2012-10-10 | 2014-04-17 | Vitas Pharma Research Pvt Ltd | Inhibitors of dna gyrase for the treatment of bacterial infections |
| TW201429972A (zh) | 2013-01-09 | 2014-08-01 | Actelion Pharmaceuticals Ltd | 抗菌噁唑酮衍生物 |
| AR096135A1 (es) | 2013-05-02 | 2015-12-09 | Actelion Pharmaceuticals Ltd | Derivados de la quinolona |
| JP6546654B2 (ja) | 2014-08-22 | 2019-07-17 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | 淋菌感染を治療するための三環式含窒素化合物 |
| UY36851A (es) | 2015-08-16 | 2017-03-31 | Glaxosmithkline Ip Dev Ltd | Compuestos para uso en aplicaciones antibacterianas |
| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
| US20220106308A1 (en) | 2019-02-19 | 2022-04-07 | Univerza V Ljubljani | Antibacterials based on monocyclic fragments coupled to aminopiperidine naphthyridine scaffold |
| EP4045908A1 (en) | 2019-10-18 | 2022-08-24 | The Regents Of The University Of California | Ex vivo tumor angiogenesis model |
| EP4045485A1 (en) | 2019-10-18 | 2022-08-24 | The Regents Of The University Of California | 3-phenylsulphonyl-quinoline derivatives as agents for treating pathogenic blood vessels disorders |
Family Cites Families (40)
| 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 |
| JP2539504B2 (ja) | 1987-03-11 | 1996-10-02 | 鐘淵化学工業株式会社 | ヒドロキシスチレン誘導体 |
| 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 |
| KR100330553B1 (ko) | 1993-10-01 | 2002-11-27 | 노파르티스 아게 | 약물학적활성피리딘유도체및그의제조방법 |
| 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 |
| HUT76853A (en) | 1994-11-14 | 1997-12-29 | Warner Lambert Co | 6-aryl pyrido[2,3-d]pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation and pharmaceutical compositions containing the same |
| KR19990008051A (ko) | 1995-04-26 | 1999-01-25 | 히라타다다시 | 라디시콜 유도체 |
| US5620997A (en) | 1995-05-31 | 1997-04-15 | Warner-Lambert Company | Isothiazolones |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| US6077857A (en) | 1995-11-13 | 2000-06-20 | 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 |
| AU2898297A (en) | 1996-05-24 | 1998-01-05 | Novartis Ag | Use of substance p antagonists for treating social phobia |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| DE69908555T2 (de) | 1998-01-26 | 2004-05-06 | Smithkline Beecham P.L.C., Brentford | Chinolinderivate als antibakterielles arzneimittel |
| GB9822440D0 (en) | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| GB9822450D0 (en) | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| EP1144404A1 (en) * | 1999-01-20 | 2001-10-17 | 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 |
| 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 |
| CZ2003243A3 (cs) | 2000-07-26 | 2003-09-17 | Smithkline Beecham P. L. C. | Aminopiperidinové chinoliny a jejich azaisosterické analogy s antibakteriální aktivitou |
| 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 |
| GB0031086D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031088D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| 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 |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112834D0 (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 |
-
2001
- 2001-01-22 GB GBGB0101577.5A patent/GB0101577D0/en not_active Ceased
-
2002
- 2002-01-22 AT AT02702296T patent/ATE370731T1/de not_active IP Right Cessation
- 2002-01-22 JP JP2002557390A patent/JP4472928B2/ja not_active Expired - Lifetime
- 2002-01-22 ES ES02702296T patent/ES2292716T3/es not_active Expired - Lifetime
- 2002-01-22 DE DE60221969T patent/DE60221969T2/de not_active Expired - Lifetime
- 2002-01-22 EP EP02702296A patent/EP1359908B1/en not_active Expired - Lifetime
- 2002-01-22 US US10/466,394 patent/US7205408B2/en not_active Expired - Fee Related
- 2002-01-22 WO PCT/EP2002/000587 patent/WO2002056882A1/en not_active Ceased
-
2009
- 2009-11-02 JP JP2009251653A patent/JP2010024246A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| GB0101577D0 (en) | 2001-03-07 |
| JP2004520360A (ja) | 2004-07-08 |
| WO2002056882A1 (en) | 2002-07-25 |
| JP4472928B2 (ja) | 2010-06-02 |
| DE60221969T2 (de) | 2008-04-30 |
| US20040138219A1 (en) | 2004-07-15 |
| US7205408B2 (en) | 2007-04-17 |
| DE60221969D1 (de) | 2007-10-04 |
| EP1359908B1 (en) | 2007-08-22 |
| EP1359908A1 (en) | 2003-11-12 |
| ATE370731T1 (de) | 2007-09-15 |
| JP2010024246A (ja) | 2010-02-04 |
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