DE60030847T2 - Antiinfektiöse makrolidderivate - Google Patents
Antiinfektiöse makrolidderivate Download PDFInfo
- Publication number
- DE60030847T2 DE60030847T2 DE60030847T DE60030847T DE60030847T2 DE 60030847 T2 DE60030847 T2 DE 60030847T2 DE 60030847 T DE60030847 T DE 60030847T DE 60030847 T DE60030847 T DE 60030847T DE 60030847 T2 DE60030847 T2 DE 60030847T2
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- 230000002924 anti-infective effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 298
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 13
- 125000006239 protecting group Chemical group 0.000 claims abstract description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 125000005018 aryl alkenyl group Chemical group 0.000 claims abstract description 10
- 125000005015 aryl alkynyl group Chemical group 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- -1 azidoethyl Chemical group 0.000 claims description 152
- 238000000034 method Methods 0.000 claims description 96
- 239000000463 material Substances 0.000 claims description 36
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 9
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 claims description 6
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 6
- 230000000813 microbial effect Effects 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 229910052731 fluorine Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 239000011737 fluorine Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 102
- 150000002923 oximes Chemical class 0.000 abstract description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 3
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 231
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 204
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 159
- 238000006243 chemical reaction Methods 0.000 description 130
- 239000000243 solution Substances 0.000 description 116
- 238000002360 preparation method Methods 0.000 description 111
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 97
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- 235000019439 ethyl acetate Nutrition 0.000 description 82
- 239000012267 brine Substances 0.000 description 73
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
- 239000000741 silica gel Substances 0.000 description 58
- 229910002027 silica gel Inorganic materials 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 53
- 239000000047 product Substances 0.000 description 48
- 229920006395 saturated elastomer Polymers 0.000 description 48
- 238000004587 chromatography analysis Methods 0.000 description 45
- 238000007792 addition Methods 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 35
- 230000015572 biosynthetic process Effects 0.000 description 34
- 239000000543 intermediate Substances 0.000 description 34
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- 230000002829 reductive effect Effects 0.000 description 32
- 125000001424 substituent group Chemical group 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 238000003756 stirring Methods 0.000 description 29
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- 229910052757 nitrogen Inorganic materials 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- 239000012043 crude product Substances 0.000 description 26
- 239000000284 extract Substances 0.000 description 25
- ZGIKWINFUGEQEO-UHFFFAOYSA-N 3-bromoquinoline Chemical compound C1=CC=CC2=CC(Br)=CN=C21 ZGIKWINFUGEQEO-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 16
- 238000003818 flash chromatography Methods 0.000 description 15
- HQZOLNNEQAKEHT-UHFFFAOYSA-N (3R,4S,5R,6S,7S,9R,11R,12S,13R,14R)-14-ethyl-4,6,12-trihydroxy-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione Natural products CCC1OC(=O)C(C)C(O)C(C)C(O)C(C)CC(C)C(=O)C(C)C(O)C1C HQZOLNNEQAKEHT-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- 108010030975 Polyketide Synthases Proteins 0.000 description 14
- 238000000855 fermentation Methods 0.000 description 14
- 230000004151 fermentation Effects 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 0 **C(C(*)C1)*(*)OC1=C Chemical compound **C(C(*)C1)*(*)OC1=C 0.000 description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 235000010633 broth Nutrition 0.000 description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 241000187559 Saccharopolyspora erythraea Species 0.000 description 12
- 239000000908 ammonium hydroxide Substances 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 229960003276 erythromycin Drugs 0.000 description 12
- 239000003120 macrolide antibiotic agent Substances 0.000 description 12
- 239000002002 slurry Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 11
- 239000003835 ketolide antibiotic agent Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- 150000007970 thio esters Chemical class 0.000 description 11
- 241000187432 Streptomyces coelicolor Species 0.000 description 10
- HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 10
- 238000010511 deprotection reaction Methods 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 229910004298 SiO 2 Inorganic materials 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 239000002054 inoculum Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 229930001119 polyketide Natural products 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 238000011068 loading method Methods 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 150000003881 polyketide derivatives Chemical class 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
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- AXFZADXWLMXITO-UHFFFAOYSA-N N-acetylcysteamine Chemical compound CC(=O)NCCS AXFZADXWLMXITO-UHFFFAOYSA-N 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- HRNGDAQBEIFYGL-UHFFFAOYSA-N 3,4-dihydroxy-4-tetradeca-3,6-dienoyloxybutanoic acid Chemical compound CCCCCCCC=CCC=CCC(=O)OC(O)C(O)CC(O)=O HRNGDAQBEIFYGL-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 239000002168 alkylating agent Substances 0.000 description 6
- 229940100198 alkylating agent Drugs 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000001212 derivatisation Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000013587 production medium Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- CAFPEYWNLASVHQ-JKNGSDSYSA-N (3r,4s,5r,6s,7s,9r,11r,12s,13r,14r)-4,6,12-trihydroxy-3,5,7,9,11,13-hexamethyl-14-propyl-oxacyclotetradecane-2,10-dione Chemical compound CCC[C@H]1OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@@H](C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H]1C CAFPEYWNLASVHQ-JKNGSDSYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 229930006677 Erythromycin A Natural products 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 235000011089 carbon dioxide Nutrition 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- AJSDVNKVGFVAQU-BIIVOSGPSA-N cladinose Chemical group O=CC[C@@](C)(OC)[C@@H](O)[C@H](C)O AJSDVNKVGFVAQU-BIIVOSGPSA-N 0.000 description 5
- 229930193775 erythronolide Natural products 0.000 description 5
- ZFBRGCCVTUPRFQ-UHFFFAOYSA-N erythronolide-B Natural products CCC1OC(=O)C(C)C(O)C(C)C(O)C(C)(O)CC(C)C(=O)C(C)C(O)C1C ZFBRGCCVTUPRFQ-UHFFFAOYSA-N 0.000 description 5
- 125000000468 ketone group Chemical group 0.000 description 5
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 239000003039 volatile agent Substances 0.000 description 5
- GHJOZLKJWAGCCB-AEGPPILISA-N (4s)-4-benzyl-3-[(2s,3r)-3-hydroxy-2-methylhexanoyl]-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)[C@@H](C)[C@H](O)CCC)[C@H]1CC1=CC=CC=C1 GHJOZLKJWAGCCB-AEGPPILISA-N 0.000 description 4
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- YHVUVJYEERGYNU-UHFFFAOYSA-N 4',8-Di-Me ether-5,7,8-Trihydroxy-3-(4-hydroxybenzyl)-4-chromanone Natural products COC1(C)CC(O)OC(C)C1O YHVUVJYEERGYNU-UHFFFAOYSA-N 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 4
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
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- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 101150020232 ptpA gene Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- ALQUTEKNDPODSS-UHFFFAOYSA-N quinoline-4-carbaldehyde-oxime Natural products C1=CC=C2C(C=NO)=CC=NC2=C1 ALQUTEKNDPODSS-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- 239000002594 sorbent Substances 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
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- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical compound C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23B—PRESERVATION OF FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES; CHEMICAL RIPENING OF FRUIT OR VEGETABLES
- A23B2/00—Preservation of foods or foodstuffs, in general
- A23B2/70—Preservation of foods or foodstuffs, in general by treatment with chemicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Food Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US550045 | 1995-10-30 | ||
| US12972999P | 1999-04-16 | 1999-04-16 | |
| US129729P | 1999-04-16 | ||
| US14017599P | 1999-06-18 | 1999-06-18 | |
| US140175P | 1999-06-18 | ||
| US17215499P | 1999-12-17 | 1999-12-17 | |
| US17215999P | 1999-12-17 | 1999-12-17 | |
| US172159P | 1999-12-17 | ||
| US172154P | 1999-12-17 | ||
| US17380499P | 1999-12-30 | 1999-12-30 | |
| US17380599P | 1999-12-30 | 1999-12-30 | |
| US173804P | 1999-12-30 | ||
| US173805P | 1999-12-30 | ||
| PCT/US2000/009914 WO2000063224A2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| US09/550,045 US6395710B1 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60030847D1 DE60030847D1 (de) | 2006-11-02 |
| DE60030847T2 true DE60030847T2 (de) | 2007-04-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60030847T Expired - Fee Related DE60030847T2 (de) | 1999-04-16 | 2000-04-14 | Antiinfektiöse makrolidderivate |
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| US (3) | US6395710B1 (enExample) |
| EP (1) | EP1171446B1 (enExample) |
| JP (1) | JP2003523938A (enExample) |
| KR (2) | KR20020007374A (enExample) |
| CN (1) | CN1241931C (enExample) |
| AT (1) | ATE340183T1 (enExample) |
| AU (2) | AU773678B2 (enExample) |
| BR (1) | BR0010680A (enExample) |
| CA (1) | CA2369816A1 (enExample) |
| DE (1) | DE60030847T2 (enExample) |
| ES (1) | ES2272273T3 (enExample) |
| ID (1) | ID30547A (enExample) |
| IL (2) | IL145777A0 (enExample) |
| MX (1) | MXPA01010524A (enExample) |
| NZ (1) | NZ515027A (enExample) |
| WO (2) | WO2000063225A2 (enExample) |
Families Citing this family (37)
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| AP1060A (en) * | 1998-01-02 | 2002-04-23 | Pfizer Prod Inc | Novel erythromycin derivatives. |
| HRP20010559A2 (en) | 1999-01-27 | 2002-08-31 | Pfizer Prod Inc | Ketolide antibiotics |
| US6451768B1 (en) | 1999-04-16 | 2002-09-17 | Kosan Biosciences, Inc. | Macrolide antiinfective agents |
| US6590083B1 (en) * | 1999-04-16 | 2003-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | Ketolide antibacterials |
| EP1167376B1 (en) | 2000-06-30 | 2004-07-14 | Pfizer Products Inc. | Macrolide antibiotics |
| US6472372B1 (en) | 2000-12-06 | 2002-10-29 | Ortho-Mcneil Pharmaceuticals, Inc. | 6-O-Carbamoyl ketolide antibacterials |
| JP4554158B2 (ja) * | 2001-03-21 | 2010-09-29 | ダウ・アグロサイエンス・エル・エル・シー | 有害生物防除性スピノシン誘導体 |
| JP2005503416A (ja) | 2001-09-17 | 2005-02-03 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | ６−ｏ−カルバメート−１１，１２−ラクト−ケトライド抗菌剤 |
| HUP0500018A3 (en) | 2001-12-05 | 2009-09-28 | Ortho Mcneil Pharm Inc | 6-o-acyl ketolide derivatives of erythromycine processes for preparing them and using them as antibacterials |
| US8063021B2 (en) * | 2002-01-17 | 2011-11-22 | Kosan Biosciences Incorporated | Ketolide anti-infective compounds |
| AU2003218110A1 (en) | 2002-03-12 | 2003-09-29 | Bristol-Myers Squibb Company | C3-cyano epothilone derivatives |
| US20040014691A1 (en) * | 2002-04-25 | 2004-01-22 | Searle Xenia Beebe | 9-Oxime macrolide antibacterials |
| US20040009932A1 (en) * | 2002-04-26 | 2004-01-15 | Kathleen Phelan | Antibacterial compounds with activity against penicillin-resistant streptococcus pneumoniae |
| AU2003234650A1 (en) | 2002-05-31 | 2003-12-19 | Janssen Pharmaceutica N.V. | 3-descladinosyl-6-o-carbamoyl and 6-o-carbonoyl macrolide antibacterial agents |
| WO2004003169A2 (en) | 2002-06-28 | 2004-01-08 | Kosan Biosciences, Inc. | Recombinant genes for polyketide modifying enzymes |
| ATE417856T1 (de) * | 2002-08-29 | 2009-01-15 | Pfizer | Motilidverbindungen |
| CA2529817C (en) * | 2003-03-10 | 2013-02-12 | Optimer Pharmaceuticals, Inc. | Novel antibacterial agents |
| US7407941B2 (en) * | 2003-08-26 | 2008-08-05 | Pfizer, Inc. | N-desmethyl-N-substituted-11-deoxyerythromycin compounds |
| US20050113319A1 (en) * | 2003-08-26 | 2005-05-26 | Christopher Carreras | 11-Deoxy-6,9-ether erythromycin compounds |
| US6953782B2 (en) * | 2003-12-24 | 2005-10-11 | Enanta Pharmaceuticals, Inc. | 11-C-substituted erythromycin derivatives |
| CA2591746A1 (en) * | 2004-12-21 | 2006-06-29 | Pfizer Products Inc. | Macrolides |
| US7595300B2 (en) | 2005-12-13 | 2009-09-29 | Kosan Biosciences Incorporated | 7-quinolyl ketolide antibacterial agents |
| EP2214484A4 (en) * | 2007-10-25 | 2013-01-02 | Cempra Pharmaceuticals Inc | PROCESS FOR PREPARING ANTIBACTERIAL MAKROLIDE AGENTS |
| KR101589960B1 (ko) * | 2008-02-08 | 2016-01-29 | 바실리어 파마슈티카 아게 | Ｐｄｅ 억제를 통해 중재되는 질환의 치료를 위한 마크로라이드 |
| WO2010048601A1 (en) | 2008-10-24 | 2010-04-29 | Cempra Pharmaceuticals, Inc. | Biodefenses using triazole-containing macrolides |
| US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
| CN102724874B (zh) | 2009-09-10 | 2018-06-01 | 森普拉制药公司 | 治疗疟疾、结核病和mac疾病的方法 |
| US8975386B2 (en) | 2010-03-22 | 2015-03-10 | Cempra Pharmaceuticals, Inc. | Crystalline forms of a macrolide, and uses therefor |
| EP2571506B1 (en) | 2010-05-20 | 2017-05-10 | Cempra Pharmaceuticals, Inc. | Processes for preparing macrolides and ketolides and intermediates therefor |
| US8796474B1 (en) | 2010-08-23 | 2014-08-05 | Rutgers, The State University Of New Jersey | Macrolide compounds and methods and intermediates useful for their preparation |
| KR20180110181A (ko) | 2010-09-10 | 2018-10-08 | 셈프라 파마슈티컬스, 인크. | 질환을 치료하기 위한 수소결합 형성 플루오로 케토라이드 |
| EP2681222B1 (en) * | 2011-03-01 | 2018-02-28 | Wockhardt Limited | Process for preparation of ketolide intermediates |
| CN104470527B (zh) | 2012-03-27 | 2019-05-28 | 森普拉制药公司 | 用于施用大环内酯抗生素的肠胃外制剂 |
| CN102718816B (zh) * | 2012-07-11 | 2014-11-05 | 山东大学 | 4''-O-(反式-β-芳基烯丙酰胺)氨基甲酰基阿奇霉素衍生物 |
| CN105163785A (zh) | 2013-03-14 | 2015-12-16 | 森普拉制药公司 | 用于治疗呼吸道疾病的方法及其制剂 |
| WO2014145210A1 (en) | 2013-03-15 | 2014-09-18 | Cempra Pharmaceuticals, Inc. | Convergent processes for preparing macrolide antibacterial agents |
| US20230174567A1 (en) * | 2020-05-22 | 2023-06-08 | Merck Sharp & Dohme Llc | Synthesis of fluorinated nucleotides |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US5141926A (en) | 1990-04-18 | 1992-08-25 | Abbott Laboratories | Erythromycin derivatives |
| IL99995A (en) * | 1990-11-21 | 1997-11-20 | Roussel Uclaf | Erythromycin derivatives, their preparation and pharmaceutical compositions containing them |
| US5523399A (en) * | 1991-12-27 | 1996-06-04 | Taisho Pharmaceutical Co., Ltd. | 5-O-desosaminylerythronolide derivatives |
| JP3259429B2 (ja) * | 1992-04-22 | 2002-02-25 | 大正製薬株式会社 | ５−ｏ−デソサミニルエリスロノライドａ誘導体 |
| US5527780A (en) | 1992-11-05 | 1996-06-18 | Roussel Uclaf | Erythromycin derivatives |
| US6066721A (en) | 1995-07-06 | 2000-05-23 | Stanford University | Method to produce novel polyketides |
| US5672491A (en) | 1993-09-20 | 1997-09-30 | The Leland Stanford Junior University | Recombinant production of novel polyketides |
| FR2718450B1 (fr) * | 1994-04-08 | 1997-01-10 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
| FR2719587B1 (fr) | 1994-05-03 | 1996-07-12 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
| AU706445B2 (en) | 1995-07-06 | 1999-06-17 | Brown University Research Foundation | Cell-free synthesis of polyketides |
| FR2739620B1 (fr) * | 1995-10-09 | 1997-12-19 | Roussel Uclaf | Nouveaux derives de la 5-0-desosaminyl 6-o-methyl erythronolide a, leur procede de preparation et leur application a la preparation de produits biologiquement actifs |
| US6274715B1 (en) | 1995-11-08 | 2001-08-14 | Abbott Laboratories | Tricyclic erythromycin derivatives |
| FR2742757B1 (fr) | 1995-12-22 | 1998-01-30 | Roussel Uclaf | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
| AU726075B2 (en) * | 1996-05-07 | 2000-10-26 | Abbott Laboratories | 6-o-substituted erythromycin compounds and method for making same |
| US5750510A (en) * | 1997-04-04 | 1998-05-12 | Abbott Laboratories | 3-descladinose-2,3-anhydroerythromycin derivatives |
| FR2748746B1 (fr) | 1996-05-14 | 1998-08-14 | Hoechst Marion Roussel Inc | Nouveau procede d'isomerisation du radical methyle en 10 de derives de l'erythromycine |
| EP0909327B1 (en) | 1996-07-05 | 2005-06-01 | Biotica Technology Limited | Erythromycins and process for their preparation |
| US6271255B1 (en) | 1996-07-05 | 2001-08-07 | Biotica Technology Limited | Erythromycins and process for their preparation |
| FR2751656B1 (fr) * | 1996-07-24 | 1998-10-16 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
| UA51730C2 (uk) | 1996-09-04 | 2002-12-16 | Ебботт Лабораторіз | 6-o-заміщені кетоліди з антибактеріальною активністю, спосіб їх одержання (варіанти), фармацевтична композиція та спосіб регулювання бактеріальної інфекції у ссавців |
| DE69733422T2 (de) * | 1996-09-04 | 2006-05-04 | Abbott Laboratories, Abbott Park | 6-0-substituierte ketoliden mit antibakteriellen wirkung |
| FR2754821B1 (fr) * | 1996-10-23 | 2003-04-04 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
| AU4472797A (en) * | 1996-10-31 | 1998-05-22 | Taisho Pharmaceutical Co., Ltd. | Erythromycin a derivatives |
| FR2757168B1 (fr) * | 1996-12-12 | 1999-06-11 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
| CA2279259A1 (en) * | 1997-02-04 | 1998-08-06 | Abbott Laboratories | Pain reducing parenteral liposome formulation |
| FR2760017B1 (fr) * | 1997-02-27 | 1999-04-30 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erytromycine, leur procede de preparation et leur application comme medicaments |
| TR199902995T2 (xx) * | 1997-06-11 | 2000-02-21 | Pfizer Products Inc. | 9-Oksim eritromisin t�revleri |
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| US6124269A (en) | 1997-10-29 | 2000-09-26 | Abbott Laboratories | 2-Halo-6-O-substituted ketolide derivatives |
| JP2004514643A (ja) * | 1997-10-29 | 2004-05-20 | 大正製薬株式会社 | エリスロマイシンａ誘導体 |
| CO4990960A1 (es) * | 1997-10-29 | 2000-12-26 | Abbott Lab | Derivados de cetolidos 2-halo-6-o sustituidos |
| AP1060A (en) * | 1998-01-02 | 2002-04-23 | Pfizer Prod Inc | Novel erythromycin derivatives. |
| DK0941998T3 (da) | 1998-03-03 | 2004-09-20 | Pfizer Prod Inc | 3,6-ketalmakrolidantibiotika |
| FR2777282B1 (fr) | 1998-04-08 | 2001-04-20 | Hoechst Marion Roussel Inc | Nouveaux derives de la 2-fluoro 3-de((2,6-dideoxy 3-c-methyl 3-0-methyl-alpha-l-ribohexopyranosyl) oxyl) 6-o-methyl 3-oxo erythromycine, leur procede de preparation et leur application a la synthese de principes actifs de medicaments |
| ATE243219T1 (de) * | 1998-04-24 | 2003-07-15 | Pfizer Prod Inc | 9a, 11b-dehydro derivative von 9-oxime-3-keto-6-0-methylerythromycin |
| FR2781484B1 (fr) * | 1998-07-21 | 2001-08-10 | Hoechst Marion Roussel Inc | Nouveaux derives de la 6-deoxy erythromycine, leur procede de preparation et leur application comme medicaments |
| CA2347412A1 (en) | 1998-10-29 | 2000-05-11 | Kosan Biosciences, Inc. | Recombinant oleandolide polyketide synthase |
| AU5995299A (en) | 1998-11-03 | 2000-05-22 | Pfizer Products Inc. | Novel macrolide antibiotics |
| TR200102129T2 (tr) | 1998-12-10 | 2002-01-21 | Pfizer Products Inc. | Karbamat ve karbazat ketolid antibiyotikleri. |
| HRP20010559A2 (en) | 1999-01-27 | 2002-08-31 | Pfizer Prod Inc | Ketolide antibiotics |
| WO2000055168A1 (en) * | 1999-03-15 | 2000-09-21 | Abbott Laboratories | 6-o-substituted macrolides having antibacterial activity |
| US6399582B1 (en) * | 1999-04-16 | 2002-06-04 | Ortho-Mcneil Pharmaceutical, Inc. | Ketolide antibacterials |
| BR0010938A (pt) | 1999-05-24 | 2002-03-19 | Pfizer Prod Inc | Derivados da 13-metil eritromicina |
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2000
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- 2000-04-14 ES ES00922149T patent/ES2272273T3/es not_active Expired - Lifetime
- 2000-04-14 ID IDW00200102465A patent/ID30547A/id unknown
- 2000-04-14 AT AT00922149T patent/ATE340183T1/de not_active IP Right Cessation
- 2000-04-14 JP JP2000612314A patent/JP2003523938A/ja active Pending
- 2000-04-14 IL IL14577700A patent/IL145777A0/xx active IP Right Grant
- 2000-04-14 DE DE60030847T patent/DE60030847T2/de not_active Expired - Fee Related
- 2000-04-14 BR BR0010680-1A patent/BR0010680A/pt not_active IP Right Cessation
- 2000-04-14 KR KR1020017013225A patent/KR20020007374A/ko not_active Withdrawn
- 2000-04-14 WO PCT/US2000/009915 patent/WO2000063225A2/en not_active Ceased
- 2000-04-14 KR KR1020017013150A patent/KR100710605B1/ko not_active Expired - Fee Related
- 2000-04-14 MX MXPA01010524A patent/MXPA01010524A/es active IP Right Grant
- 2000-04-14 EP EP00922149A patent/EP1171446B1/en not_active Expired - Lifetime
- 2000-04-14 NZ NZ515027A patent/NZ515027A/xx unknown
- 2000-04-14 CA CA002369816A patent/CA2369816A1/en not_active Abandoned
- 2000-04-14 US US09/550,045 patent/US6395710B1/en not_active Expired - Lifetime
- 2000-04-14 AU AU42379/00A patent/AU773678B2/en not_active Ceased
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- 2000-04-14 AU AU44578/00A patent/AU775637B2/en not_active Ceased
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2001
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2002
- 2002-02-13 US US10/075,466 patent/US6593302B2/en not_active Ceased
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2005
- 2005-07-13 US US11/182,038 patent/USRE39836E1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR100710605B1 (ko) | 2007-04-24 |
| WO2000063224A3 (en) | 2001-01-18 |
| ES2272273T3 (es) | 2007-05-01 |
| US6395710B1 (en) | 2002-05-28 |
| EP1171446A2 (en) | 2002-01-16 |
| WO2000063225A3 (en) | 2001-01-18 |
| BR0010680A (pt) | 2002-02-19 |
| IL145777A0 (en) | 2002-07-25 |
| JP2003523938A (ja) | 2003-08-12 |
| AU4457800A (en) | 2000-11-02 |
| ID30547A (id) | 2001-12-20 |
| US20020119938A1 (en) | 2002-08-29 |
| MXPA01010524A (es) | 2002-03-14 |
| IL145777A (en) | 2007-02-11 |
| AU4237900A (en) | 2000-11-02 |
| ATE340183T1 (de) | 2006-10-15 |
| CN1384838A (zh) | 2002-12-11 |
| US6593302B2 (en) | 2003-07-15 |
| KR20020007374A (ko) | 2002-01-26 |
| NZ515027A (en) | 2004-01-30 |
| AU775637B2 (en) | 2004-08-12 |
| WO2000063225A2 (en) | 2000-10-26 |
| KR20020007372A (ko) | 2002-01-26 |
| WO2000063224A2 (en) | 2000-10-26 |
| CN1241931C (zh) | 2006-02-15 |
| DE60030847D1 (de) | 2006-11-02 |
| USRE39836E1 (en) | 2007-09-11 |
| AU773678B2 (en) | 2004-06-03 |
| EP1171446B1 (en) | 2006-09-20 |
| CA2369816A1 (en) | 2000-10-26 |
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