JP4445753B2 - アミノピペリジン誘導体 - Google Patents
アミノピペリジン誘導体 Download PDFInfo
- Publication number
- JP4445753B2 JP4445753B2 JP2003564044A JP2003564044A JP4445753B2 JP 4445753 B2 JP4445753 B2 JP 4445753B2 JP 2003564044 A JP2003564044 A JP 2003564044A JP 2003564044 A JP2003564044 A JP 2003564044A JP 4445753 B2 JP4445753 B2 JP 4445753B2
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- pyrido
- ethyl
- piperidin
- methyl
- 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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- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical class NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 206
- -1 4H-benzo [1,4] thiazin-3-one-6-yl Chemical group 0.000 claims description 205
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- XYBYNVQWRLVUCY-UHFFFAOYSA-N 2-methoxy-1,5-naphthyridine Chemical compound N1=CC=CC2=NC(OC)=CC=C21 XYBYNVQWRLVUCY-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- UIRSLBDCOYTZPH-UHFFFAOYSA-N 4h-1,4-thiazin-3-one Chemical compound O=C1CSC=CN1 UIRSLBDCOYTZPH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000006414 CCl Chemical group ClC* 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- PMGCOACZJUNQHT-HJNYFJLDSA-N 6-[[[(3r,4s)-3-fluoro-1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CN[C@H]3CCN(C[C@H]3F)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 PMGCOACZJUNQHT-HJNYFJLDSA-N 0.000 claims description 4
- YAAHHYJAMOXGRR-HJNYFJLDSA-N 6-[[[(3r,4s)-3-fluoro-1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CCN(C[C@H]3F)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CC=C21 YAAHHYJAMOXGRR-HJNYFJLDSA-N 0.000 claims description 4
- WJAKHOJSUXKJOB-CBQOVEMMSA-N 7-chloro-6-[[[(3r,4s)-3-fluoro-1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound N1C(=O)CSC(C=C2Cl)=C1N=C2CN[C@H]([C@H](F)C1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 WJAKHOJSUXKJOB-CBQOVEMMSA-N 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- IYCPHKXDNHTLDA-ZXBWEVJXSA-N 2-[[[(3R,4S)-3-fluoro-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 S1C2=CC=CC=C2NC(=O)C1CN[C@H]([C@H](F)C1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)N=C21 IYCPHKXDNHTLDA-ZXBWEVJXSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- OYYHTHWUDCUBQV-UHFFFAOYSA-N 1,4-thiazin-2-one Chemical compound O=C1C=NC=CS1 OYYHTHWUDCUBQV-UHFFFAOYSA-N 0.000 claims description 2
- BJIFLZHRWYQMPW-MOPGFXCFSA-N 6-[[[(3r,4s)-1-[2-(2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-10-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CCN(CCC=4C5=C6OCCOC6=CC=C5N=CC=4)C[C@H]3F)=CC=C21 BJIFLZHRWYQMPW-MOPGFXCFSA-N 0.000 claims description 2
- QTLGOLHPVBIPDT-IRLDBZIGSA-N 6-[[[(3r,4s)-1-[2-(3-chloro-6-methoxyquinolin-4-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CCN(C[C@H]3F)CCC3=C(Cl)C=NC4=CC=C(C=C43)OC)=CC=C21 QTLGOLHPVBIPDT-IRLDBZIGSA-N 0.000 claims description 2
- OSGFFHMWNXQDSU-UXHICEINSA-N 6-[[[(3r,4s)-1-[2-(6,8-difluoroquinolin-4-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CCN(CCC=4C5=CC(F)=CC(F)=C5N=CC=4)C[C@H]3F)=CC=C21 OSGFFHMWNXQDSU-UXHICEINSA-N 0.000 claims description 2
- YZZJHGZBYQEOCV-HKBOAZHASA-N 6-[[[(3r,4s)-3-fluoro-1-[(2r)-2-(8-fluoro-6-methoxyquinolin-4-yl)-2-hydroxyethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical compound O1CC(=O)NC2=NC(CN[C@H]3CCN(C[C@H]3F)C[C@H](O)C3=CC=NC4=C(F)C=C(C=C43)OC)=CC=C21 YZZJHGZBYQEOCV-HKBOAZHASA-N 0.000 claims description 2
- QADVLLAVDNVSTJ-HKBOAZHASA-N 6-[[[(3r,4s)-3-fluoro-1-[(2r)-2-(8-fluoro-6-methoxyquinolin-4-yl)-2-hydroxyethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@H]3CCN(C[C@H]3F)C[C@H](O)C3=CC=NC4=C(F)C=C(C=C43)OC)=CC=C21 QADVLLAVDNVSTJ-HKBOAZHASA-N 0.000 claims description 2
- DAUHOSXWTKANFE-MSOLQXFVSA-N 6-[[[(3r,4s)-3-fluoro-1-[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(CN[C@H]3CCN(C[C@H]3F)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 DAUHOSXWTKANFE-MSOLQXFVSA-N 0.000 claims description 2
- VAJYNKKDUHJUSD-DWLFOUALSA-N 7-fluoro-6-[[[(3s,4r)-3-fluoro-1-[(2r)-2-hydroxy-2-(6-methoxyquinolin-4-yl)ethyl]piperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound N1C(=O)CSC(C=C2F)=C1N=C2CN[C@@H]([C@@H](F)C1)CCN1C[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 VAJYNKKDUHJUSD-DWLFOUALSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- BJIFLZHRWYQMPW-RBUKOAKNSA-N 6-[[[(3s,4r)-1-[2-(2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-10-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@@H]3CCN(CCC=4C5=C6OCCOC6=CC=C5N=CC=4)C[C@@H]3F)=CC=C21 BJIFLZHRWYQMPW-RBUKOAKNSA-N 0.000 claims 1
- QTLGOLHPVBIPDT-RBBKRZOGSA-N 6-[[[(3s,4r)-1-[2-(3-chloro-6-methoxyquinolin-4-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@@H]3CCN(C[C@@H]3F)CCC3=C(Cl)C=NC4=CC=C(C=C43)OC)=CC=C21 QTLGOLHPVBIPDT-RBBKRZOGSA-N 0.000 claims 1
- OSGFFHMWNXQDSU-VQTJNVASSA-N 6-[[[(3s,4r)-1-[2-(6,8-difluoroquinolin-4-yl)ethyl]-3-fluoropiperidin-4-yl]amino]methyl]-4h-pyrido[3,2-b][1,4]thiazin-3-one Chemical compound S1CC(=O)NC2=NC(CN[C@@H]3CCN(CCC=4C5=CC(F)=CC(F)=C5N=CC=4)C[C@@H]3F)=CC=C21 OSGFFHMWNXQDSU-VQTJNVASSA-N 0.000 claims 1
- DAUHOSXWTKANFE-ZWKOTPCHSA-N 6-[[[(3s,4r)-3-fluoro-1-[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(CN[C@@H]3CCN(C[C@@H]3F)CCC3=CC=NC4=CC=C(N=C43)OC)=CC=C21 DAUHOSXWTKANFE-ZWKOTPCHSA-N 0.000 claims 1
- APOCZZJMKPPBAE-NWSQWKLXSA-N 7-[[[(3r,4s)-3-fluoro-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(CN[C@H]3CCN(C[C@H]3F)C[C@H](O)C3=CC=NC4=CC=C(C=C43)OC)=CN=C21 APOCZZJMKPPBAE-NWSQWKLXSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 191
- 239000000243 solution Substances 0.000 description 149
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 139
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 120
- 238000000034 method Methods 0.000 description 117
- 238000006243 chemical reaction Methods 0.000 description 116
- 230000002829 reductive effect Effects 0.000 description 107
- 239000000203 mixture Substances 0.000 description 105
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000007787 solid Substances 0.000 description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 87
- 125000000217 alkyl group Chemical group 0.000 description 83
- 150000001412 amines Chemical class 0.000 description 82
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- 239000000741 silica gel Substances 0.000 description 56
- 229910002027 silica gel Inorganic materials 0.000 description 56
- 150000001299 aldehydes Chemical class 0.000 description 55
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 53
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- 235000019441 ethanol Nutrition 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 33
- 239000000463 material Substances 0.000 description 32
- 239000011734 sodium Substances 0.000 description 32
- 239000012458 free base Substances 0.000 description 28
- 150000002500 ions Chemical class 0.000 description 27
- 239000002253 acid Substances 0.000 description 26
- 229910052763 palladium Inorganic materials 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 24
- 150000002148 esters Chemical class 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 17
- 125000003277 amino group Chemical group 0.000 description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 125000000623 heterocyclic group Chemical group 0.000 description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- 230000009467 reduction Effects 0.000 description 16
- 238000006722 reduction reaction Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 15
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 14
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 238000007796 conventional method Methods 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 229910052736 halogen Inorganic materials 0.000 description 11
- 150000002367 halogens Chemical class 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 229910052760 oxygen Inorganic materials 0.000 description 11
- 239000012279 sodium borohydride Substances 0.000 description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 10
- 125000005137 alkenylsulfonyl group Chemical group 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- DWPWWTIOOLQURY-NWDGAFQWSA-N benzyl n-[(3s,4r)-3-fluoropiperidin-4-yl]carbamate Chemical compound F[C@H]1CNCC[C@H]1NC(=O)OCC1=CC=CC=C1 DWPWWTIOOLQURY-NWDGAFQWSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 150000002118 epoxides Chemical class 0.000 description 10
- 150000002431 hydrogen Chemical group 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 8
- 241000283690 Bos taurus Species 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 239000012948 isocyanate Substances 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 125000004043 oxo group Chemical group O=* 0.000 description 8
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- NCROKCAMKHFNJK-DQPZFDDXSA-N (1r)-2-(4-amino-3-fluoropiperidin-1-yl)-1-(6-methoxyquinolin-4-yl)ethanol Chemical compound C([C@H](O)C1=CC=NC2=CC=C(C=C21)OC)N1CCC(N)C(F)C1 NCROKCAMKHFNJK-DQPZFDDXSA-N 0.000 description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 7
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 7
- XXLFLUJXWKXUGS-UHFFFAOYSA-N 6-methoxyquinoline-4-carboxylic acid Chemical compound N1=CC=C(C(O)=O)C2=CC(OC)=CC=C21 XXLFLUJXWKXUGS-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 150000002513 isocyanates Chemical class 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
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- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- JXBLMDWEOQDVAC-HUUCEWRRSA-N tert-butyl (3r,4r)-4-(benzylamino)-3-fluoropiperidine-1-carboxylate Chemical compound F[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1NCC1=CC=CC=C1 JXBLMDWEOQDVAC-HUUCEWRRSA-N 0.000 description 1
- MPEHODVZNZDDNF-BMFZPTHFSA-N tert-butyl (3r,4s)-4-[[(1r)-1-phenylethyl]amino]-3-(trifluoromethyl)piperidine-1-carboxylate Chemical compound N([C@H](C)C=1C=CC=CC=1)[C@H]1CCN(C(=O)OC(C)(C)C)C[C@H]1C(F)(F)F MPEHODVZNZDDNF-BMFZPTHFSA-N 0.000 description 1
- ZQRYPCAUVKVMLZ-JGVFFNPUSA-N tert-butyl (3s,4r)-4-amino-3-fluoropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)[C@@H](F)C1 ZQRYPCAUVKVMLZ-JGVFFNPUSA-N 0.000 description 1
- CQWAEPLMMYOMSW-UHFFFAOYSA-N tert-butyl 2-[(4-aminophenyl)methyl]-3-fluoropiperidine-1-carboxylate Chemical class CC(C)(C)OC(=O)N1CCCC(F)C1CC1=CC=C(N)C=C1 CQWAEPLMMYOMSW-UHFFFAOYSA-N 0.000 description 1
- ZMBOAZOGDOOGDB-UHFFFAOYSA-N tert-butyl 2-amino-3-fluoropiperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1C(C(CCC1)F)N ZMBOAZOGDOOGDB-UHFFFAOYSA-N 0.000 description 1
- XITWENTVYSRHII-UHFFFAOYSA-N tert-butyl 4-[(3-oxo-4h-1,4-benzothiazin-6-yl)methylamino]-4-(trifluoromethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C(F)(F)F)NCC1=CC=C(SCC(=O)N2)C2=C1 XITWENTVYSRHII-UHFFFAOYSA-N 0.000 description 1
- NYPUFDUCDMKIGM-UHFFFAOYSA-N tert-butyl 4-amino-4-(trifluoromethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)(C(F)(F)F)CC1 NYPUFDUCDMKIGM-UHFFFAOYSA-N 0.000 description 1
- OFXIZIWLUBEIKG-UHFFFAOYSA-N tert-butyl 4-benzyl-3-fluoropiperidine-1-carboxylate Chemical compound FC1CN(C(=O)OC(C)(C)C)CCC1CC1=CC=CC=C1 OFXIZIWLUBEIKG-UHFFFAOYSA-N 0.000 description 1
- OAKIKPITPDYEAD-UHFFFAOYSA-N tert-butyl 4-oxo-3-(trifluoromethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C(C(F)(F)F)C1 OAKIKPITPDYEAD-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PXONPRNGXXSDFW-FVQBIDKESA-N tert-butyl n-[(2r,4r)-1-[(1r)-1-phenylethyl]-2-(trifluoromethyl)piperidin-4-yl]carbamate Chemical compound N1([C@H](C)C=2C=CC=CC=2)CC[C@@H](NC(=O)OC(C)(C)C)C[C@@H]1C(F)(F)F PXONPRNGXXSDFW-FVQBIDKESA-N 0.000 description 1
- PXONPRNGXXSDFW-VNQPRFMTSA-N tert-butyl n-[(2r,4s)-1-[(1r)-1-phenylethyl]-2-(trifluoromethyl)piperidin-4-yl]carbamate Chemical compound N1([C@H](C)C=2C=CC=CC=2)CC[C@H](NC(=O)OC(C)(C)C)C[C@@H]1C(F)(F)F PXONPRNGXXSDFW-VNQPRFMTSA-N 0.000 description 1
- CLRHEWHZVXLJFX-COXVUDFISA-N tert-butyl n-[(2s,4r)-1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2-(trifluoromethyl)piperidin-4-yl]carbamate Chemical compound C([C@H](O)C1=CC=NC2=CC=C(N=C21)OC)N1CC[C@@H](NC(=O)OC(C)(C)C)C[C@H]1C(F)(F)F CLRHEWHZVXLJFX-COXVUDFISA-N 0.000 description 1
- CLRHEWHZVXLJFX-JQFCIGGWSA-N tert-butyl n-[(2s,4s)-1-[(2r)-2-hydroxy-2-(6-methoxy-1,5-naphthyridin-4-yl)ethyl]-2-(trifluoromethyl)piperidin-4-yl]carbamate Chemical compound C([C@H](O)C1=CC=NC2=CC=C(N=C21)OC)N1CC[C@H](NC(=O)OC(C)(C)C)C[C@H]1C(F)(F)F CLRHEWHZVXLJFX-JQFCIGGWSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 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
- 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
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000004897 thiazines Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 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
- 238000009901 transfer hydrogenation reaction Methods 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
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 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
- JPFRZOQKRGLTAC-UHFFFAOYSA-N trifluoromethanesulfonate;1-(trifluoromethyl)dibenzothiophen-5-ium Chemical compound [O-]S(=O)(=O)C(F)(F)F.[SH+]1C2=CC=CC=C2C2=C1C=CC=C2C(F)(F)F JPFRZOQKRGLTAC-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
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-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
- 238000009827 uniform distribution Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
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| GB0229824A GB0229824D0 (en) | 2002-12-20 | 2002-12-20 | Compounds |
| PCT/EP2003/000823 WO2003064421A1 (en) | 2002-01-29 | 2003-01-27 | Aminopiperidine derivatives |
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| JP2005525324A JP2005525324A (ja) | 2005-08-25 |
| JP2005525324A5 JP2005525324A5 (enExample) | 2006-01-12 |
| JP4445753B2 true JP4445753B2 (ja) | 2010-04-07 |
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| EP (2) | EP1470125A1 (enExample) |
| JP (1) | JP4445753B2 (enExample) |
| AR (1) | AR038240A1 (enExample) |
| TW (1) | TW200406410A (enExample) |
| WO (1) | WO2003064421A1 (enExample) |
Cited By (1)
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| JP2006511622A (ja) * | 2002-12-18 | 2006-04-06 | グラクソ グループ リミテッド | 抗菌剤 |
Families Citing this family (53)
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| US6803369B1 (en) | 2000-07-25 | 2004-10-12 | Smithkline Beecham Corporation | Compounds and methods for the treatment of neoplastic disease |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112834D0 (en) * | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0118238D0 (en) * | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
| WO2003064431A2 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| AR040335A1 (es) * | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
| TW200409637A (en) * | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| DE60331849D1 (de) * | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| AU2003291227A1 (en) | 2002-11-05 | 2004-06-07 | Smithkline Beecham Corporation | Antibacterial agents |
| WO2004050036A2 (en) * | 2002-12-04 | 2004-06-17 | Glaxo Group Limited | Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents |
| FR2858619B1 (fr) * | 2003-08-08 | 2006-12-22 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leurs procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| US7348434B2 (en) | 2003-08-08 | 2008-03-25 | Antony Bigot | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| ES2436888T3 (es) | 2003-09-26 | 2014-01-07 | Exelixis, Inc | Moduladores c-Met y métodos de uso |
| US7691850B2 (en) * | 2004-06-15 | 2010-04-06 | Glaxo Group Limited | Antibacterial agents |
| EP1773831A1 (en) * | 2004-07-08 | 2007-04-18 | Glaxo Group Limited | Antibacterial agents |
| DE602005024151D1 (de) * | 2004-08-02 | 2010-11-25 | Glaxo Group Ltd | Antibakterielle mittel |
| DE102004041163A1 (de) * | 2004-08-25 | 2006-03-02 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen mit antibakterieller Aktivität |
| JP4887297B2 (ja) * | 2004-09-24 | 2012-02-29 | アクテリオン ファーマシューティカルズ リミテッド | 新規二環式抗生物質 |
| WO2006081179A1 (en) * | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| WO2006081178A2 (en) * | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| WO2006081182A2 (en) | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| WO2006081289A2 (en) * | 2005-01-25 | 2006-08-03 | Glaxo Group Limited | Antibacterial agents |
| US7605169B2 (en) | 2005-01-25 | 2009-10-20 | Glaxo Group Limited | Antibacterial agents |
| EP1863483A4 (en) | 2005-03-31 | 2010-03-31 | Janssen Pharmaceutica Nv | Bicyclic pyrazole compounds as anti-bacteriostatic agents |
| MY150958A (en) | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
| EP1790342A1 (de) | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
| US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
| JP2009524643A (ja) * | 2006-01-26 | 2009-07-02 | アクテリオン ファーマシューティカルズ リミテッド | テトラヒドロピラン抗生物質 |
| DE602007010427D1 (de) * | 2006-02-15 | 2010-12-23 | Actelion Pharmaceuticals Ltd | Antibiotische ethanol- oder 1,2-ethandiol-cyclohexyl-derivate |
| EP1991531A1 (en) * | 2006-02-28 | 2008-11-19 | Amgen Inc. | Cinnoline and quinoxaline derivates as phosphodiesterase 10 inhibitors |
| MX2008011220A (es) * | 2006-03-07 | 2008-09-11 | Array Biopharma Inc | Compuestos de pirazol heterobiciclicos y metodos de uso. |
| EP2001887B1 (en) | 2006-04-06 | 2010-09-15 | Glaxo Group Limited | Pyrrolo-quinoxalinone derivatives as antibacterials |
| EP2007377A4 (en) | 2006-04-06 | 2011-08-17 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| US20100256124A1 (en) * | 2006-06-09 | 2010-10-07 | David Thomas Davies | Substituted 1-Methyl-1H-Quinolin-2-Ones And 1-Methyl-1H-1,5-Naphthyridin-2-Ones As Antibacterials |
| GB0613208D0 (en) | 2006-07-03 | 2006-08-09 | Glaxo Group Ltd | Compounds |
| EP1992628A1 (en) | 2007-05-18 | 2008-11-19 | Glaxo Group Limited | Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones |
| TW200819457A (en) * | 2006-08-30 | 2008-05-01 | Actelion Pharmaceuticals Ltd | Spiro antibiotic derivatives |
| CA2684659C (en) | 2007-04-20 | 2015-11-24 | Glaxo Group Limited | Tricyclic nitrogen containing compounds as antibacterial agents |
| EP2080761A1 (en) | 2008-01-18 | 2009-07-22 | Glaxo Group Limited | Compounds |
| WO2009128019A1 (en) | 2008-04-15 | 2009-10-22 | Actelion Pharmaceuticals Ltd | Tricyclic antibiotics |
| WO2010043714A1 (en) | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
| KR101297450B1 (ko) * | 2008-12-12 | 2013-08-20 | 액테리온 파마슈티칼 리미티드 | 5-아미노-2-(1-하이드록시-에틸)-테트라하이드로피란 유도체 |
| JP5653935B2 (ja) | 2009-01-15 | 2015-01-14 | グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ | 抗菌薬として有用なナフチリジン―２（１ｈ）−オン化合物 |
| CA2995880C (en) | 2009-01-16 | 2021-01-05 | Exelixis, Inc. | Processes for preparing n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| US9059778B2 (en) * | 2011-01-07 | 2015-06-16 | Integrated Device Technology Inc. | Frequency domain compression in a base transceiver system |
| JP5918624B2 (ja) * | 2012-05-18 | 2016-05-18 | 東ソ−・エフテック株式会社 | 光学活性含フッ素５，６−ジヒドロピリドン誘導体及びその製造方法 |
| CN102702080B (zh) * | 2012-06-21 | 2014-02-19 | 扬州氟药科技有限公司 | 一种3-三氟甲基哌啶衍生物的制备方法 |
| WO2016004297A1 (en) * | 2014-07-02 | 2016-01-07 | Board Of Regents, The University Of Texas System | Novel inhibitors of trypanosoma brucei methionyl t-rna synthetase (tb metrs) for the treatment of african trypanosomiasis |
| WO2016027249A1 (en) | 2014-08-22 | 2016-02-25 | Glaxosmithkline Intellectual Property Development Limited | Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection |
| TW201722965A (zh) | 2015-08-16 | 2017-07-01 | 葛蘭素史密斯克藍智慧財產發展有限公司 | 用於抗菌應用之化合物 |
| CN114957114A (zh) * | 2021-02-26 | 2022-08-30 | 冷志 | 一种4-溴-3-氯-7-甲氧基喹啉的合成方法 |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE330945C (de) | 1918-06-11 | 1920-12-21 | Ver Chininfabriken Zimmer & Co | Verfahren zur Darstellung von Chinolylketonen |
| GB1345872A (en) | 1970-09-03 | 1974-02-06 | Wyeth John & Brother Ltd | Amino-and acylamino-pyridine and hydropyridine derivatives |
| BE786529A (fr) | 1971-07-23 | 1973-01-22 | Ciba Geigy | Nouveaux derives de la diazepine et procedes pour leur preparation |
| US3989691A (en) | 1973-01-05 | 1976-11-02 | Princeton University | Preparation of cinchona alkaloid intermediates |
| GB1537867A (en) | 1977-07-04 | 1979-01-04 | Wyeth John & Brother Ltd | Process for preparing 4-acylamino-piperidine derivatives |
| FR2471981A1 (fr) | 1979-12-21 | 1981-06-26 | Pharmindustrie | Nouveaux derives de la (piperidyl-4)-2 (quinolyl-4)-1 ethanone, produits intermediaires et procedes pour leur preparation, et leur utilisation comme medicaments |
| FR2495470A1 (fr) | 1980-12-05 | 1982-06-11 | Pharmindustrie | Nouveaux medicaments a base de derives de (quinolyl-4)-1 (piperidyl-4)-2 ethanol ou (quinolyl-4)-1 (piperidyl-4)-3 propanol |
| US4925877A (en) | 1986-02-25 | 1990-05-15 | Zaidanhojin Biseibutsu Kagaku Kenkyukai | Physiologically active erbstatin analogue compounds and compositions |
| DE3874257T2 (de) | 1987-03-11 | 1993-02-11 | Kanegafuchi Chemical Ind | Hydroxystyren-derivate. |
| 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 |
| ATE208772T1 (de) | 1993-10-01 | 2001-11-15 | Novartis Erfind Verwalt Gmbh | Pharmacologisch wirksame pyridinderivate und verfahren zu deren herstellung |
| 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 |
| AU711426B2 (en) | 1994-11-14 | 1999-10-14 | Warner-Lambert Company | 6-aryl pyrido(2,3-d)pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| JP3938936B2 (ja) | 1995-04-26 | 2007-06-27 | 協和醗酵工業株式会社 | ラディシコール誘導体 |
| US5620997A (en) | 1995-05-31 | 1997-04-15 | Warner-Lambert Company | Isothiazolones |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| WO1997017957A1 (en) | 1995-11-13 | 1997-05-22 | 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 |
| CA2318842A1 (en) | 1998-01-26 | 1999-07-29 | Julie Dorothy Warrack | Quinoline derivatives as antibacterials |
| GB9822440D0 (en) | 1998-10-14 | 1998-12-09 | Smithkline Beecham Plc | Medicaments |
| GB9822450D0 (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 |
| GB9917406D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| GB9917408D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| US6403610B1 (en) | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| 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 |
| 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 |
| GB0031088D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0031086D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| US6602884B2 (en) | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| 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 |
| WO2003064431A2 (en) * | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
| AR040335A1 (es) | 2002-06-26 | 2005-03-30 | Glaxo Group Ltd | Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto |
| GB0217294D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| FR2844270B1 (fr) | 2002-09-11 | 2006-05-19 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur procede et intermediaires de preparation et les compositions qui les contiennent |
| FR2844268B1 (fr) | 2002-09-11 | 2004-10-22 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leurs procedes et intermediaires de preparation et les compositions qui les contiennent |
| AU2003301414B8 (en) | 2002-10-10 | 2010-06-17 | Morphochem Aktiengesellschaft Fur Kombinatorische Chemie | Novel compounds with antibacterial activity |
| AU2003291227A1 (en) | 2002-11-05 | 2004-06-07 | Smithkline Beecham Corporation | Antibacterial agents |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| WO2004050036A2 (en) | 2002-12-04 | 2004-06-17 | 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 |
-
2003
- 2003-01-27 WO PCT/EP2003/000823 patent/WO2003064421A1/en not_active Ceased
- 2003-01-27 EP EP03734701A patent/EP1470125A1/en not_active Ceased
- 2003-01-27 TW TW092101651A patent/TW200406410A/zh unknown
- 2003-01-27 US US10/502,233 patent/US7312212B2/en not_active Expired - Fee Related
- 2003-01-27 JP JP2003564044A patent/JP4445753B2/ja not_active Expired - Fee Related
- 2003-01-27 AR ARP030100233A patent/AR038240A1/es not_active Application Discontinuation
- 2003-01-27 EP EP09172606A patent/EP2181996A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006511622A (ja) * | 2002-12-18 | 2006-04-06 | グラクソ グループ リミテッド | 抗菌剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005525324A (ja) | 2005-08-25 |
| EP1470125A1 (en) | 2004-10-27 |
| EP2181996A1 (en) | 2010-05-05 |
| WO2003064421A1 (en) | 2003-08-07 |
| AR038240A1 (es) | 2005-01-05 |
| TW200406410A (en) | 2004-05-01 |
| US20050159411A1 (en) | 2005-07-21 |
| US7312212B2 (en) | 2007-12-25 |
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