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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- 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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| GB9822440D0 (en) | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| JP2002535323A (ja) * | 1999-01-20 | 2002-10-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | プロテインキナーゼ阻害剤としてのピペリジニルキノリン |
| GB9914486D0 (en) * | 1999-06-21 | 1999-08-18 | Smithkline Beecham Plc | Medicaments |
| GB9917408D0 (en) * | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| GB9917406D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| FR2798656B1 (fr) | 1999-09-17 | 2004-12-17 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6403610B1 (en) * | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| US6803369B1 (en) * | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| DE60125373T2 (de) * | 2000-07-26 | 2007-10-18 | Smithkline Beecham P.L.C., Brentford | Aminopiperidin chinoline und ihre azaisosteren analoga mit antibakterieller wirkung |
| EP1719770A3 (en) * | 2000-09-21 | 2008-03-05 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
| FR2816618B1 (fr) | 2000-11-15 | 2002-12-27 | Aventis Pharma Sa | Derives heterocyclylalcoyl piperidine, leur preparation et les compositions qui les contiennent |
| US6603005B2 (en) * | 2000-11-15 | 2003-08-05 | Aventis Pharma S.A. | Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them |
| GB0031086D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031088D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| US6602884B2 (en) * | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| 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 |
| GB0112834D0 (en) * | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US20030203917A1 (en) * | 2001-07-25 | 2003-10-30 | Smithkline Beecham Corporation And Smithkline Beecham P.L.C. | Compounds and methods for the treatment of neoplastic disease |
| GB0118238D0 (en) * | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
-
2001
- 2001-01-22 GB GBGB0101577.5A patent/GB0101577D0/en not_active Ceased
-
2002
- 2002-01-22 JP JP2002557390A patent/JP4472928B2/ja not_active Expired - Lifetime
- 2002-01-22 AT AT02702296T patent/ATE370731T1/de not_active IP Right Cessation
- 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 ES ES02702296T patent/ES2292716T3/es not_active Expired - Lifetime
- 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 |
|---|---|
| ATE370731T1 (de) | 2007-09-15 |
| DE60221969D1 (de) | 2007-10-04 |
| JP4472928B2 (ja) | 2010-06-02 |
| US20040138219A1 (en) | 2004-07-15 |
| WO2002056882A1 (en) | 2002-07-25 |
| EP1359908A1 (en) | 2003-11-12 |
| EP1359908B1 (en) | 2007-08-22 |
| JP2010024246A (ja) | 2010-02-04 |
| GB0101577D0 (en) | 2001-03-07 |
| DE60221969T2 (de) | 2008-04-30 |
| JP2004520360A (ja) | 2004-07-08 |
| US7205408B2 (en) | 2007-04-17 |
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