DE60215951T2 - Piperidinderivate als antibakterielle mittel - Google Patents
Piperidinderivate als antibakterielle mittel Download PDFInfo
- Publication number
- DE60215951T2 DE60215951T2 DE60215951T DE60215951T DE60215951T2 DE 60215951 T2 DE60215951 T2 DE 60215951T2 DE 60215951 T DE60215951 T DE 60215951T DE 60215951 T DE60215951 T DE 60215951T DE 60215951 T2 DE60215951 T2 DE 60215951T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- hydroxy
- methoxy
- dihydro
- naphthyridin
- 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 - Fee Related
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims description 131
- 230000000259 anti-tumor effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 158
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 5
- 241000124008 Mammalia Species 0.000 claims abstract description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 5
- -1 amino, piperidyl Chemical group 0.000 claims description 241
- 150000001875 compounds Chemical class 0.000 claims description 187
- 125000000217 alkyl group Chemical group 0.000 claims description 150
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 63
- 230000008569 process Effects 0.000 claims description 50
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 150000001408 amides Chemical class 0.000 claims description 40
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 38
- 125000003277 amino group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 35
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 33
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 22
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 21
- 150000003254 radicals Chemical class 0.000 claims description 21
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 238000005984 hydrogenation reaction Methods 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 9
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 229910052721 tungsten Inorganic materials 0.000 claims description 8
- 125000000852 azido group Chemical group *N=[N+]=[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 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 229940079593 drug Drugs 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
- 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
- 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 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
- 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
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 150000003950 cyclic amides Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 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
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims 3
- DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims 2
- OWKUCOSIMPSMJB-UHFFFAOYSA-N 6-amino-4H-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound NC1=NC=2NC(=O)CSC=2C=C1 OWKUCOSIMPSMJB-UHFFFAOYSA-N 0.000 claims 2
- 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
- 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 1
- INHNYISGOBHQRE-UHFFFAOYSA-N 1-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxyethyl]-4-hydroxypiperidine-4-carboxylic acid Chemical compound C=1C=C2OCCOC2=CC=1C(O)CN1CCC(O)(C(O)=O)CC1 INHNYISGOBHQRE-UHFFFAOYSA-N 0.000 claims 1
- SAHVHRAUICTINS-UHFFFAOYSA-N 1-[2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)ethyl]-4-hydroxypiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(O)CCN1CCC(N=C1)=CC2=C1OCCO2 SAHVHRAUICTINS-UHFFFAOYSA-N 0.000 claims 1
- QQYKHNDMZIEFOO-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 Chemical compound O1CCOC(C=N2)=C1C=C2CCN(CC1)CCC1(O)C(=O)NC1=CC=NC2=C(F)C=C(OC)C=C21 QQYKHNDMZIEFOO-UHFFFAOYSA-N 0.000 claims 1
- AESLRYMZADOVDA-UHFFFAOYSA-N 1-[2-(6-oxo-5h-pyridazino[3,4-b][1,4]thiazin-3-yl)ethyl]-4-(trifluoromethyl)piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(C(F)(F)F)CCN1CCC(N=N1)=CC2=C1SCC(=O)N2 AESLRYMZADOVDA-UHFFFAOYSA-N 0.000 claims 1
- KVFOPXJUIFFQCE-UHFFFAOYSA-N 4-(hydroxymethyl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylic acid Chemical compound C1CC(CO)(C(O)=O)CCN1CCC1=CC=C(SCC(=O)N2)C2=C1 KVFOPXJUIFFQCE-UHFFFAOYSA-N 0.000 claims 1
- AURXPTQXLKNFGN-LBPRGKRZSA-N 4-hydroxy-1-[(2R)-2-hydroxy-2-(3-oxo-4H-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylic acid Chemical compound C([C@H](O)C=1C=C2NC(=O)CSC2=CC=1)N1CCC(O)(C(O)=O)CC1 AURXPTQXLKNFGN-LBPRGKRZSA-N 0.000 claims 1
- MRCSWAQDADAHKJ-UHFFFAOYSA-N 4-hydroxy-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(O)CCN1CCC1=CC=C(SCC(=O)N2)C2=C1 MRCSWAQDADAHKJ-UHFFFAOYSA-N 0.000 claims 1
- KUOGISAKTSYBBS-UHFFFAOYSA-N 4-hydroxy-1-[2-(6-oxo-5h-pyridazino[3,4-b][1,4]thiazin-3-yl)ethyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(O)CCN1CCC(N=N1)=CC2=C1SCC(=O)N2 KUOGISAKTSYBBS-UHFFFAOYSA-N 0.000 claims 1
- LSDGNRVKQMOICF-UHFFFAOYSA-N 4-hydroxy-1-[2-oxo-2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(O)CCN1CC(=O)C1=CC=C(SCC(=O)N2)C2=C1 LSDGNRVKQMOICF-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 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 323
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 200
- 239000000243 solution Substances 0.000 description 130
- 238000006243 chemical reaction Methods 0.000 description 120
- 239000000203 mixture Substances 0.000 description 119
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 114
- 150000002500 ions Chemical class 0.000 description 114
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 74
- 239000007787 solid Substances 0.000 description 66
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- 150000002148 esters Chemical class 0.000 description 43
- 239000000377 silicon dioxide Substances 0.000 description 43
- 238000004587 chromatography analysis Methods 0.000 description 42
- 235000019441 ethanol Nutrition 0.000 description 42
- 150000001412 amines Chemical class 0.000 description 40
- 239000012458 free base Substances 0.000 description 39
- 239000002253 acid Substances 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- 239000000284 extract Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 22
- 150000001299 aldehydes Chemical class 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 229960001866 silicon dioxide Drugs 0.000 description 19
- 239000012279 sodium borohydride Substances 0.000 description 19
- 229910000033 sodium borohydride Inorganic materials 0.000 description 19
- 229960004756 ethanol Drugs 0.000 description 18
- 238000001704 evaporation Methods 0.000 description 18
- 230000008020 evaporation Effects 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 230000009467 reduction Effects 0.000 description 17
- 238000006722 reduction reaction Methods 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 230000007062 hydrolysis Effects 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 150000003839 salts Chemical class 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 150000001732 carboxylic acid derivatives Chemical class 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
- 230000002829 reductive effect Effects 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 11
- 229910021529 ammonia Inorganic materials 0.000 description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 241000283690 Bos taurus Species 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 235000006408 oxalic acid Nutrition 0.000 description 10
- 150000002924 oxiranes Chemical class 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 9
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
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- 238000006053 organic reaction Methods 0.000 description 1
- 125000001181 organosilyl group Chemical class [SiH3]* 0.000 description 1
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- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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- 235000011007 phosphoric acid Nutrition 0.000 description 1
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- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- FHLACKYUBOGPPD-UHFFFAOYSA-N piperidine-1,4,4-tricarboxylic acid Chemical compound OC(=O)N1CCC(C(O)=O)(C(O)=O)CC1 FHLACKYUBOGPPD-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
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- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
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- 150000004892 pyridazines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
- VSGPVHSTVTXREH-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C[C]2C(=O)C=CN=C21 VSGPVHSTVTXREH-UHFFFAOYSA-N 0.000 description 1
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 description 1
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- 239000001632 sodium acetate Substances 0.000 description 1
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
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- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
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- 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
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- 230000002194 synthesizing effect Effects 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
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- 235000002906 tartaric acid Nutrition 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
- TYVWNTKLAZUAMY-UHFFFAOYSA-N tert-butyl 2-(6-methoxy-1,5-naphthyridin-4-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C12=NC(OC)=CC=C2N=CC=C1N(C1=O)CCC21CCN(C(=O)OC(C)(C)C)CC2 TYVWNTKLAZUAMY-UHFFFAOYSA-N 0.000 description 1
- HZBBLCVWKNGCBS-UHFFFAOYSA-N tert-butyl 4-(1,5-naphthyridin-4-ylcarbamoyl)-1-[2-(3-oxo-4h-1,4-benzothiazin-6-yl)ethyl]piperidine-4-carboxylate Chemical compound C1=CN=C2C(NC(=O)C3(CCN(CCC=4C=C5NC(=O)CSC5=CC=4)CC3)C(=O)OC(C)(C)C)=CC=NC2=C1 HZBBLCVWKNGCBS-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
- 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
- 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
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000004897 thiazines Chemical class 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
- 238000012546 transfer Methods 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
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-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
- 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
- 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
- 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
- 238000010792 warming Methods 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
- 150000007934 α,β-unsaturated carboxylic acids Chemical class 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0118238 | 2001-07-26 | ||
| 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 |
|---|---|
| DE60215951D1 DE60215951D1 (de) | 2006-12-21 |
| DE60215951T2 true DE60215951T2 (de) | 2007-04-26 |
Family
ID=9919236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60215951T Expired - Fee Related DE60215951T2 (de) | 2001-07-26 | 2002-07-25 | Piperidinderivate als antibakterielle mittel |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20040198756A1 (https=) |
| EP (1) | EP1419155B1 (https=) |
| JP (1) | JP2005504747A (https=) |
| AT (1) | ATE344799T1 (https=) |
| AU (1) | AU2002328972A1 (https=) |
| DE (1) | DE60215951T2 (https=) |
| ES (1) | ES2274999T3 (https=) |
| GB (1) | GB0118238D0 (https=) |
| WO (1) | WO2003010138A2 (https=) |
Families Citing this family (54)
| 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 |
| WO2002024684A1 (en) * | 2000-09-21 | 2002-03-28 | Smithkline Beecham P.L.C. | 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 |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| EP1470131A2 (en) | 2002-01-29 | 2004-10-27 | 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 |
| 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 |
| EP1551829B1 (de) | 2002-10-10 | 2010-04-07 | Morphochem Aktiengesellschaft Für Kombinatorische Chemie | Neue verbindungen mit antibakterieller aktivität |
| EP1560488B1 (en) | 2002-11-05 | 2010-09-01 | Glaxo Group Limited | Antibacterial agents |
| US7232832B2 (en) | 2002-11-05 | 2007-06-19 | Smithkline Beecham Corporation | Antibacterial agents |
| AR042486A1 (es) * | 2002-12-18 | 2005-06-22 | Glaxo Group Ltd | Compuesto de quinolina y naftiridina halosustituido en la posicion 3, procedimiento para preparar el compuesto, composicion farmaceutica que lo comprende y su uso para preparar dicha composicion . |
| EP1720873B1 (en) | 2004-01-08 | 2011-02-23 | F. Hoffmann-La Roche AG | Diaza-spiropiperidine derivatives |
| 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 |
| CA2584502A1 (en) | 2004-06-24 | 2006-01-05 | Incyte Corporation | 2-methylpropanamides and their use as pharmaceuticals |
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-
2001
- 2001-07-26 GB GBGB0118238.5A patent/GB0118238D0/en not_active Ceased
-
2002
- 2002-07-25 EP EP02764786A patent/EP1419155B1/en not_active Expired - Lifetime
- 2002-07-25 WO PCT/EP2002/008319 patent/WO2003010138A2/en not_active Ceased
- 2002-07-25 ES ES02764786T patent/ES2274999T3/es not_active Expired - Lifetime
- 2002-07-25 US US10/484,563 patent/US20040198756A1/en not_active Abandoned
- 2002-07-25 AU AU2002328972A patent/AU2002328972A1/en not_active Abandoned
- 2002-07-25 AT AT02764786T patent/ATE344799T1/de not_active IP Right Cessation
- 2002-07-25 JP JP2003515497A patent/JP2005504747A/ja active Pending
- 2002-07-25 DE DE60215951T patent/DE60215951T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60215951D1 (de) | 2006-12-21 |
| WO2003010138A3 (en) | 2003-12-04 |
| EP1419155B1 (en) | 2006-11-08 |
| US20040198756A1 (en) | 2004-10-07 |
| ATE344799T1 (de) | 2006-11-15 |
| AU2002328972A1 (en) | 2003-02-17 |
| EP1419155A2 (en) | 2004-05-19 |
| GB0118238D0 (en) | 2001-09-19 |
| ES2274999T3 (es) | 2007-06-01 |
| JP2005504747A (ja) | 2005-02-17 |
| WO2003010138A2 (en) | 2003-02-06 |
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