KR20020007374A - 매크롤라이드 항감염제 - Google Patents
매크롤라이드 항감염제 Download PDFInfo
- Publication number
- KR20020007374A KR20020007374A KR1020017013225A KR20017013225A KR20020007374A KR 20020007374 A KR20020007374 A KR 20020007374A KR 1020017013225 A KR1020017013225 A KR 1020017013225A KR 20017013225 A KR20017013225 A KR 20017013225A KR 20020007374 A KR20020007374 A KR 20020007374A
- Authority
- KR
- South Korea
- Prior art keywords
- substituted
- unsubstituted
- compound
- methyl
- formula
- 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.)
- Withdrawn
Links
- 239000004599 antimicrobial Substances 0.000 title abstract description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 title description 13
- 229960005475 antiinfective agent Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 150
- -1 di-substituted amino carbonyl Chemical group 0.000 claims abstract description 80
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 150000002923 oximes Chemical class 0.000 claims abstract description 44
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 12
- 125000006239 protecting group Chemical group 0.000 claims abstract description 12
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
- 125000005018 aryl alkenyl group Chemical group 0.000 claims abstract description 8
- 125000005015 aryl alkynyl group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 37
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 11
- 229920002554 vinyl polymer Polymers 0.000 claims description 9
- 230000000813 microbial effect Effects 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 169
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 139
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 129
- 239000000243 solution Substances 0.000 description 99
- 238000006243 chemical reaction Methods 0.000 description 80
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- 239000000047 product Substances 0.000 description 55
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- 239000012267 brine Substances 0.000 description 54
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
- 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 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 229920006395 saturated elastomer Polymers 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 229960003276 erythromycin Drugs 0.000 description 34
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 238000004587 chromatography analysis Methods 0.000 description 26
- 239000000284 extract Substances 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 238000000855 fermentation Methods 0.000 description 23
- 230000004151 fermentation Effects 0.000 description 23
- 239000000463 material Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 230000008569 process Effects 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 18
- 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 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 108010030975 Polyketide Synthases Proteins 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 235000010633 broth Nutrition 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 238000004809 thin layer chromatography Methods 0.000 description 13
- 239000012298 atmosphere Substances 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 11
- 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 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 241000187747 Streptomyces Species 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 239000002002 slurry Substances 0.000 description 10
- 150000007970 thio esters Chemical class 0.000 description 10
- 229930006677 Erythromycin A Natural products 0.000 description 9
- HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- AXFZADXWLMXITO-UHFFFAOYSA-N N-acetylcysteamine Chemical compound CC(=O)NCCS AXFZADXWLMXITO-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 238000004949 mass spectrometry Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 229930001119 polyketide Natural products 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 239000012499 inoculation medium Substances 0.000 description 7
- 235000021317 phosphate Nutrition 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 6
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 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 5
- HQZOLNNEQAKEHT-IBBGRPSASA-N 6-deoxyerythronolide B Chemical compound CC[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 HQZOLNNEQAKEHT-IBBGRPSASA-N 0.000 description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 238000011081 inoculation Methods 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 150000003881 polyketide derivatives Chemical class 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- 239000003039 volatile agent Substances 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- 241000187432 Streptomyces coelicolor Species 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000287 crude extract Substances 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 229930193775 erythronolide Natural products 0.000 description 4
- 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 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000004088 foaming agent Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000013587 production medium Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 4
- 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 3
- AUSTXZTZGUNXOD-FPMFFAJLSA-N (4s)-4-benzyl-3-[(2s,3r)-3-hydroxy-2-methylpent-4-enoyl]-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)[C@H]([C@H](O)C=C)C)[C@H]1CC1=CC=CC=C1 AUSTXZTZGUNXOD-FPMFFAJLSA-N 0.000 description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 101150065749 Churc1 gene Proteins 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- YKFRUJSEPGHZFJ-UHFFFAOYSA-N N-trimethylsilylimidazole Chemical compound C[Si](C)(C)N1C=CN=C1 YKFRUJSEPGHZFJ-UHFFFAOYSA-N 0.000 description 3
- 102100038239 Protein Churchill Human genes 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 230000005484 gravity Effects 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 125000000468 ketone group Chemical group 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 229940102396 methyl bromide Drugs 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- NRTYMEPCRDJMPZ-UHFFFAOYSA-N pyridine;2,2,2-trifluoroacetic acid Chemical compound C1=CC=NC=C1.OC(=O)C(F)(F)F NRTYMEPCRDJMPZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000005215 recombination Methods 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 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 2
- LEMWLUVPJFUNEB-CRCLSJGQSA-N (2s,3r)-3-hydroxy-2-methylpent-4-enoic acid Chemical compound OC(=O)[C@@H](C)[C@H](O)C=C LEMWLUVPJFUNEB-CRCLSJGQSA-N 0.000 description 2
- WHOBYFHKONUTMW-NSHDSACASA-N (4s)-4-benzyl-3-propanoyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)CC)[C@H]1CC1=CC=CC=C1 WHOBYFHKONUTMW-NSHDSACASA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 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 2
- 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 2
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 101100168477 Saccharopolyspora erythraea (strain ATCC 11635 / DSM 40517 / JCM 4748 / NBRC 13426 / NCIMB 8594 / NRRL 2338) eryF gene Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- NSFFHOGKXHRQEW-UHFFFAOYSA-N Thiostrepton B Natural products N1C(=O)C(C)NC(=O)C(=C)NC(=O)C(C)NC(=O)C(C(C)CC)NC(C(C2=N3)O)C=CC2=C(C(C)O)C=C3C(=O)OC(C)C(C=2SC=C(N=2)C2N=3)NC(=O)C(N=4)=CSC=4C(C(C)(O)C(C)O)NC(=O)C(N=4)CSC=4C(=CC)NC(=O)C(C(C)O)NC(=O)C(N=4)=CSC=4C21CCC=3C1=NC(C(=O)NC(=C)C(=O)NC(=C)C(N)=O)=CS1 NSFFHOGKXHRQEW-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-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)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 238000005937 allylation reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 230000022811 deglycosylation Effects 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- FYGDTMLNYKFZSV-MRCIVHHJSA-N dextrin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](CO)OC(O[C@@H]2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-MRCIVHHJSA-N 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- FAVAVMFXAKZTMV-UHFFFAOYSA-N dibutylboranyl trifluoromethanesulfonate Chemical compound CCCCB(CCCC)OS(=O)(=O)C(F)(F)F FAVAVMFXAKZTMV-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 101150117988 eryK gene Proteins 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000003835 ketolide antibiotic agent Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- CZHYJTHTVKIGAJ-UHFFFAOYSA-N n,n-diethylethanamine;hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC.CCN(CC)CC CZHYJTHTVKIGAJ-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 125000000830 polyketide group Chemical group 0.000 description 2
- 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 2
- 101150020232 ptpA gene Proteins 0.000 description 2
- MGCGJBXTNWUHQE-UHFFFAOYSA-N quinoline-4-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CC=NC2=C1 MGCGJBXTNWUHQE-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- UZLRPNHVKXCOHS-UHFFFAOYSA-N s-(2-acetamidoethyl) ethanethioate Chemical compound CC(=O)NCCSC(C)=O UZLRPNHVKXCOHS-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229930188070 thiostrepton Natural products 0.000 description 2
- NSFFHOGKXHRQEW-AIHSUZKVSA-N thiostrepton Chemical compound C([C@]12C=3SC=C(N=3)C(=O)N[C@H](C(=O)NC(/C=3SC[C@@H](N=3)C(=O)N[C@H](C=3SC=C(N=3)C(=O)N[C@H](C=3SC=C(N=3)[C@H]1N=1)[C@@H](C)OC(=O)C3=CC(=C4C=C[C@H]([C@@H](C4=N3)O)N[C@H](C(N[C@@H](C)C(=O)NC(=C)C(=O)N[C@@H](C)C(=O)N2)=O)[C@@H](C)CC)[C@H](C)O)[C@](C)(O)[C@@H](C)O)=C\C)[C@@H](C)O)CC=1C1=NC(C(=O)NC(=C)C(=O)NC(=C)C(N)=O)=CS1 NSFFHOGKXHRQEW-AIHSUZKVSA-N 0.000 description 2
- 229940063214 thiostrepton Drugs 0.000 description 2
- NSFFHOGKXHRQEW-OFMUQYBVSA-N thiostrepton A Natural products CC[C@H](C)[C@@H]1N[C@@H]2C=Cc3c(cc(nc3[C@H]2O)C(=O)O[C@H](C)[C@@H]4NC(=O)c5csc(n5)[C@@H](NC(=O)[C@H]6CSC(=N6)C(=CC)NC(=O)[C@@H](NC(=O)c7csc(n7)[C@]8(CCC(=N[C@@H]8c9csc4n9)c%10nc(cs%10)C(=O)NC(=C)C(=O)NC(=C)C(=O)N)NC(=O)[C@H](C)NC(=O)C(=C)NC(=O)[C@H](C)NC1=O)[C@@H](C)O)[C@](C)(O)[C@@H](C)O)[C@H](C)O NSFFHOGKXHRQEW-OFMUQYBVSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 2
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FLDLUCBPEXPCOB-WCBMZHEXSA-N (2S,3R)-N-acetyl-3-hydroxy-2-methyl-N-(2-sulfanylethyl)hexanamide Chemical compound C[C@H](C(=O)N(CCS)C(C)=O)[C@@H](CCC)O FLDLUCBPEXPCOB-WCBMZHEXSA-N 0.000 description 1
- IMIVWAUMTAIVPJ-XUXIUFHCSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-azaniumyl-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-methylpentanoate Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC(C)C IMIVWAUMTAIVPJ-XUXIUFHCSA-N 0.000 description 1
- WOLQREOUPKZMEX-BZSNNMDCSA-N (2s)-2-[[(4s)-4-[[(4s)-4-[[4-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]benzoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C=C1 WOLQREOUPKZMEX-BZSNNMDCSA-N 0.000 description 1
- UBEKFGMRKUQZGX-NTSWFWBYSA-N (2s,3r)-3-hydroxy-2-methylhexanoic acid Chemical compound CCC[C@@H](O)[C@H](C)C(O)=O UBEKFGMRKUQZGX-NTSWFWBYSA-N 0.000 description 1
- RWXVJMKHFBGFMJ-RIHPBJNCSA-N (2s,3r)-3-hydroxy-2-methylhexanoic acid;n-(2-sulfanylethyl)acetamide Chemical compound CC(=O)NCCS.CCC[C@@H](O)[C@H](C)C(O)=O RWXVJMKHFBGFMJ-RIHPBJNCSA-N 0.000 description 1
- ZUGIGWIPEYNYJV-FZWPAWTOSA-N (3r,4s,5r,6s,7s,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione Chemical class 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@H](C)[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 ZUGIGWIPEYNYJV-FZWPAWTOSA-N 0.000 description 1
- OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 1
- YCQANBSROMMIQP-UHFFFAOYSA-N 1-chloropyrrolidine-2,5-dione;methylsulfanylmethane Chemical compound CSC.ClN1C(=O)CCC1=O YCQANBSROMMIQP-UHFFFAOYSA-N 0.000 description 1
- VZAWCLCJGSBATP-UHFFFAOYSA-N 1-cycloundecyl-1,2-diazacycloundecane Chemical compound C1CCCCCCCCCC1N1NCCCCCCCCC1 VZAWCLCJGSBATP-UHFFFAOYSA-N 0.000 description 1
- UJVVTNYYIPMEAP-UHFFFAOYSA-N 2-(quinolin-4-ylamino)acetic acid Chemical compound C1=CC=C2C(NCC(=O)O)=CC=NC2=C1 UJVVTNYYIPMEAP-UHFFFAOYSA-N 0.000 description 1
- PVRJWJORYKSQAN-UHFFFAOYSA-N 2-(quinolin-6-ylamino)acetic acid Chemical compound N1=CC=CC2=CC(NCC(=O)O)=CC=C21 PVRJWJORYKSQAN-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- OMDOTYQVWXDXKI-UHFFFAOYSA-N 2-isoquinolin-4-ylacetyl chloride Chemical compound C1=CC=C2C(CC(=O)Cl)=CN=CC2=C1 OMDOTYQVWXDXKI-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- HTTSLVFOIBKDFR-UHFFFAOYSA-N 253607-91-9 Chemical compound C1C2C3C4C5OC6(C(F)(F)C(=O)O)C4C3C1C6C52 HTTSLVFOIBKDFR-UHFFFAOYSA-N 0.000 description 1
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- DBVTYDLZMXNRIN-UHFFFAOYSA-N 3-benzyl-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1CC1=CC=CC=C1 DBVTYDLZMXNRIN-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ICQFJLICCIUWEV-UHFFFAOYSA-N 3-hydroxy-2-methyl-n-propanoyl-n-(2-sulfanylethyl)hexanamide Chemical compound CCCC(O)C(C)C(=O)N(CCS)C(=O)CC ICQFJLICCIUWEV-UHFFFAOYSA-N 0.000 description 1
- LJGPENGDCAMAAG-UHFFFAOYSA-N 3-isoquinolin-4-ylpropanoyl chloride Chemical compound C1=CC=C2C(CCC(=O)Cl)=CN=CC2=C1 LJGPENGDCAMAAG-UHFFFAOYSA-N 0.000 description 1
- XXUOGAYBSXZFTD-UHFFFAOYSA-N 3-propanoyl-1,3-oxazolidin-2-one Chemical compound CCC(=O)N1CCOC1=O XXUOGAYBSXZFTD-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- YXGJGRFUOOCAIO-UHFFFAOYSA-N 3-quinolin-4-ylpropanoyl chloride Chemical compound C1=CC=C2C(CCC(=O)Cl)=CC=NC2=C1 YXGJGRFUOOCAIO-UHFFFAOYSA-N 0.000 description 1
- OJOFMLDBXPDXLQ-UHFFFAOYSA-N 4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)NC1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-UHFFFAOYSA-N 0.000 description 1
- GHJOZLKJWAGCCB-XSDATEAUSA-N 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)C1CC1=CC=CC=C1 GHJOZLKJWAGCCB-XSDATEAUSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- MWFRKHPRXPSWNT-UHFFFAOYSA-N Erythromycin-C Natural products CC1C(OC2C(C(CC(C)O2)N(C)C)O)C(C)(O)CC(C)C(=O)C(C)C(O)C(O)(C)C(CC)OC(=O)C(C)C1OC1CC(C)(O)C(O)C(C)O1 MWFRKHPRXPSWNT-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 241000187559 Saccharopolyspora erythraea Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 229920004482 WACKER® Polymers 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000005128 aryl amino alkyl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 101150042354 eryF gene Proteins 0.000 description 1
- YVTFLQUPRIIRFE-QUMKBVJLSA-N erythronolide A Chemical compound CC[C@H]1OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O YVTFLQUPRIIRFE-QUMKBVJLSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002338 glycosides Chemical group 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000000640 hydroxylating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical group [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- SWVMLNPDTIFDDY-FVGYRXGTSA-N methyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-FVGYRXGTSA-N 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000006385 ozonation reaction Methods 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008020 pharmaceutical preservative Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- KBZVFSSKGBFEBT-UHFFFAOYSA-N propan-2-yloxycyclohexane Chemical compound CC(C)OC1CCCCC1 KBZVFSSKGBFEBT-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 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
- 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
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 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
- 238000000926 separation method Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 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
- 239000012265 solid product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical compound C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000012138 yeast extract Substances 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)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Food Science & Technology (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 |
|---|---|---|---|
| US12972999P | 1999-04-16 | 1999-04-16 | |
| US60/129,729 | 1999-04-16 | ||
| US14017599P | 1999-06-18 | 1999-06-18 | |
| US60/140,175 | 1999-06-18 | ||
| US17215999P | 1999-12-17 | 1999-12-17 | |
| US17215499P | 1999-12-17 | 1999-12-17 | |
| US60/172,154 | 1999-12-17 | ||
| US60/172,159 | 1999-12-17 | ||
| US17380599P | 1999-12-30 | 1999-12-30 | |
| US17380499P | 1999-12-30 | 1999-12-30 | |
| US60/173,805 | 1999-12-30 | ||
| US60/173,804 | 1999-12-30 | ||
| PCT/US2000/009915 WO2000063225A2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| US09/550,045 US6395710B1 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| US??? | 2003-02-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20020007374A true KR20020007374A (ko) | 2002-01-26 |
Family
ID=27568857
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020017013150A Expired - Fee Related KR100710605B1 (ko) | 1999-04-16 | 2000-04-14 | 매크롤라이드 항감염제 |
| KR1020017013225A Withdrawn KR20020007374A (ko) | 1999-04-16 | 2000-04-14 | 매크롤라이드 항감염제 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020017013150A Expired - Fee Related KR100710605B1 (ko) | 1999-04-16 | 2000-04-14 | 매크롤라이드 항감염제 |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US6395710B1 (enExample) |
| EP (1) | EP1171446B1 (enExample) |
| JP (1) | JP2003523938A (enExample) |
| KR (2) | KR100710605B1 (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) | WO2000063224A2 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP1060A (en) * | 1998-01-02 | 2002-04-23 | Pfizer Prod Inc | Novel erythromycin derivatives. |
| OA11753A (en) | 1999-01-27 | 2005-07-19 | 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 |
| DK1373290T3 (da) * | 2001-03-21 | 2014-12-01 | Dow Agrosciences Llc | Pesticidale spinosynderivater |
| 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 |
| RU2004117082A (ru) | 2001-12-05 | 2005-04-10 | Орто-Макнейл Фармасьютикал, Инк. (Us) | Кетолидные 6-0-ацил-производные эритромицина в качестве антибактериальных средств |
| US8063021B2 (en) * | 2002-01-17 | 2011-11-22 | Kosan Biosciences Incorporated | Ketolide anti-infective compounds |
| DK1483251T3 (da) | 2002-03-12 | 2010-04-12 | Bristol Myers Squibb Co | C3-cyano-epothilon-derivater |
| 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 |
| US6825172B2 (en) | 2002-05-31 | 2004-11-30 | Janssen Pharmaceutica, Nv | 3-descladinosyl-6-O-carbamoyl and 6-O-carbonoyl macrolide antibacterial agents |
| US7427493B2 (en) | 2002-06-28 | 2008-09-23 | Kosan Biosciences Incorporated | Recombinant genes for polyketide modifying enzymes |
| SI1532131T1 (sl) * | 2002-08-29 | 2009-04-30 | Pfizer | Motilidne spojine |
| 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 |
| WO2005067919A1 (en) * | 2003-12-24 | 2005-07-28 | Enanta Pharmaceuticals, Inc. | 11-csubsituted 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 |
| AU2008316830B2 (en) * | 2007-10-25 | 2016-03-17 | Cempra Pharmaceuticals, Inc. | Process for the preparation of macrolide antibacterial agents |
| PL2247294T3 (pl) * | 2008-02-08 | 2014-09-30 | Basilea Pharmaceutica Ag | Makrolidy do leczenia chorób przez hamowanie PDE |
| WO2010048600A1 (en) * | 2008-10-24 | 2010-04-29 | Cempra Pharmaceuticals, Inc. | Methods for treating resistant diseases using triazole containing macrolides |
| US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
| US9480679B2 (en) | 2009-09-10 | 2016-11-01 | Cempra Pharmaceuticals, Inc. | Methods for treating malaria, tuberculosis and MAC diseases |
| HRP20160168T1 (hr) | 2010-03-22 | 2016-03-25 | Cempra Pharmaceuticals Inc | Kristalne forme makrolida i njihova uporaba |
| 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 |
| KR20130120458A (ko) | 2010-09-10 | 2013-11-04 | 셈프라 파마슈티컬스, 인크. | 질환을 치료하기 위한 수소결합 형성 플루오로 케토라이드 |
| WO2012117357A2 (en) * | 2011-03-01 | 2012-09-07 | Wockhardt Limited | Process for preparation of ketolide intermediates |
| WO2013148891A1 (en) | 2012-03-27 | 2013-10-03 | Cempra Pharmaceuticals, Inc. | Parenteral formulations for administering macrolide antibiotics |
| 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 |
| EP2968801B1 (en) | 2013-03-14 | 2018-09-26 | Cempra Pharmaceuticals, Inc. | Methods for treating respiratory diseases and formulations therefor |
| MX356772B (es) | 2013-03-15 | 2018-06-13 | Cempra Pharmaceuticals Inc | Procesos convergentes para la preparacion de agentes antibacterianos macrolidos. |
| EP4153189A1 (en) * | 2020-05-22 | 2023-03-29 | Merck Sharp & Dohme LLC | Synthesis of fluorinated nucleotides |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5141926A (en) * | 1990-04-18 | 1992-08-25 | Abbott Laboratories | Erythromycin derivatives |
| IL114589A (en) | 1990-11-21 | 1999-12-22 | Roussel Uclaf | Intermediates for the preparation of erythromycin derivatives |
| 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. |
| EP1493814A1 (en) | 1995-07-06 | 2005-01-05 | The Leland Stanford Junior University | 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 |
| US5750510A (en) | 1997-04-04 | 1998-05-12 | Abbott Laboratories | 3-descladinose-2,3-anhydroerythromycin derivatives |
| CA2253330C (en) * | 1996-05-07 | 2006-07-25 | Abbott Laboratories | 6-o-substituted erythromycin compounds and method for making same |
| 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 |
| US6271255B1 (en) | 1996-07-05 | 2001-08-07 | Biotica Technology Limited | Erythromycins and process for their preparation |
| EP0910633B1 (en) | 1996-07-05 | 2009-12-09 | Biotica Technology Limited | Hybrid polyketide synthase I gene |
| 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 |
| EP1291351B1 (en) * | 1996-09-04 | 2005-07-13 | Abbott Laboratories | 6-0 substituted ketolides having antibacterial activity |
| 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 |
| JP2001511780A (ja) * | 1997-02-04 | 2001-08-14 | アボツト・ラボラトリーズ | 鎮痛性非経口リポソーム配合物 |
| 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 |
| PL337606A1 (en) * | 1997-06-11 | 2000-08-28 | Pfizer Prod Inc | Derivatives of erythromycin 9-oxime |
| JP2001518476A (ja) * | 1997-09-30 | 2001-10-16 | アボット・ラボラトリーズ | 抗菌活性を有する３’−ｎ−修飾６−ｏ−置換エリスロマイシンケトライド誘導体 |
| CO4990960A1 (es) * | 1997-10-29 | 2000-12-26 | Abbott Lab | Derivados de cetolidos 2-halo-6-o sustituidos |
| WO1999021870A1 (en) * | 1997-10-29 | 1999-05-06 | Taisho Pharmaceutical Co., Ltd. | Erythromycin a 11, 12-carbamate derivatives |
| US6124269A (en) | 1997-10-29 | 2000-09-26 | Abbott Laboratories | 2-Halo-6-O-substituted ketolide derivatives |
| AP1060A (en) | 1998-01-02 | 2002-04-23 | Pfizer Prod Inc | Novel erythromycin derivatives. |
| ES2226282T3 (es) | 1998-03-03 | 2005-03-16 | Pfizer Products Inc. | Antibioticos macrilidos de 3,6-cetal. |
| 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 |
| DE69908855T2 (de) * | 1998-04-24 | 2004-05-19 | Pfizer Products Inc., Groton | 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 |
| AU758421B2 (en) | 1998-10-29 | 2003-03-20 | Kosan Biosciences, Inc. | Recombinant oleandolide polyketide synthase |
| SK5812001A3 (en) | 1998-11-03 | 2001-12-03 | Pfizer Prod Inc | Novel macrolide antibiotics |
| AU6484199A (en) | 1998-12-10 | 2000-06-26 | Pfizer Products Inc. | Carbamate and carbazate ketolide antibiotics |
| OA11753A (en) | 1999-01-27 | 2005-07-19 | Pfizer Prod Inc | Ketolide antibiotics. |
| JP2002539217A (ja) * | 1999-03-15 | 2002-11-19 | アボット・ラボラトリーズ | 抗菌活性を有する６−ｏ−置換マクロライド |
| CN1373767A (zh) * | 1999-04-16 | 2002-10-09 | 奥索-麦克尼尔药品公司 | 酮式大环内酯抗菌剂 |
| KR20020016799A (ko) | 1999-05-24 | 2002-03-06 | 데이비드 존 우드 | 13-메틸-에리트로마이신 유도체 |
-
2000
- 2000-04-14 US US09/550,045 patent/US6395710B1/en not_active Expired - Lifetime
- 2000-04-14 WO PCT/US2000/009914 patent/WO2000063224A2/en not_active Ceased
- 2000-04-14 JP JP2000612314A patent/JP2003523938A/ja active Pending
- 2000-04-14 BR BR0010680-1A patent/BR0010680A/pt not_active IP Right Cessation
- 2000-04-14 ES ES00922149T patent/ES2272273T3/es not_active Expired - Lifetime
- 2000-04-14 EP EP00922149A patent/EP1171446B1/en not_active Expired - Lifetime
- 2000-04-14 CN CNB008090718A patent/CN1241931C/zh not_active Expired - Fee Related
- 2000-04-14 AT AT00922149T patent/ATE340183T1/de not_active IP Right Cessation
- 2000-04-14 AU AU42379/00A patent/AU773678B2/en not_active Ceased
- 2000-04-14 IL IL14577700A patent/IL145777A0/xx active IP Right Grant
- 2000-04-14 NZ NZ515027A patent/NZ515027A/xx unknown
- 2000-04-14 KR KR1020017013150A patent/KR100710605B1/ko not_active Expired - Fee Related
- 2000-04-14 WO PCT/US2000/009915 patent/WO2000063225A2/en not_active Ceased
- 2000-04-14 AU AU44578/00A patent/AU775637B2/en not_active Ceased
- 2000-04-14 MX MXPA01010524A patent/MXPA01010524A/es active IP Right Grant
- 2000-04-14 ID IDW00200102465A patent/ID30547A/id unknown
- 2000-04-14 DE DE60030847T patent/DE60030847T2/de not_active Expired - Fee Related
- 2000-04-14 KR KR1020017013225A patent/KR20020007374A/ko not_active Withdrawn
- 2000-04-14 CA CA002369816A patent/CA2369816A1/en not_active Abandoned
-
2001
- 2001-10-04 IL IL145777A patent/IL145777A/en unknown
-
2002
- 2002-02-13 US US10/075,466 patent/US6593302B2/en not_active Ceased
-
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 |
| IL145777A (en) | 2007-02-11 |
| CA2369816A1 (en) | 2000-10-26 |
| WO2000063225A2 (en) | 2000-10-26 |
| AU775637B2 (en) | 2004-08-12 |
| IL145777A0 (en) | 2002-07-25 |
| NZ515027A (en) | 2004-01-30 |
| ATE340183T1 (de) | 2006-10-15 |
| AU4457800A (en) | 2000-11-02 |
| AU4237900A (en) | 2000-11-02 |
| EP1171446B1 (en) | 2006-09-20 |
| AU773678B2 (en) | 2004-06-03 |
| CN1384838A (zh) | 2002-12-11 |
| ID30547A (id) | 2001-12-20 |
| MXPA01010524A (es) | 2002-03-14 |
| DE60030847D1 (de) | 2006-11-02 |
| EP1171446A2 (en) | 2002-01-16 |
| DE60030847T2 (de) | 2007-04-19 |
| WO2000063225A3 (en) | 2001-01-18 |
| CN1241931C (zh) | 2006-02-15 |
| BR0010680A (pt) | 2002-02-19 |
| USRE39836E1 (en) | 2007-09-11 |
| JP2003523938A (ja) | 2003-08-12 |
| US20020119938A1 (en) | 2002-08-29 |
| KR20020007372A (ko) | 2002-01-26 |
| ES2272273T3 (es) | 2007-05-01 |
| WO2000063224A2 (en) | 2000-10-26 |
| US6593302B2 (en) | 2003-07-15 |
| US6395710B1 (en) | 2002-05-28 |
| WO2000063224A3 (en) | 2001-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20020007374A (ko) | 매크롤라이드 항감염제 | |
| US6399582B1 (en) | Ketolide antibacterials | |
| US6590083B1 (en) | Ketolide antibacterials | |
| US6762168B2 (en) | Macrolide antiinfective agents | |
| US6794366B2 (en) | Macrolide antiinfective agents | |
| US20030199458A1 (en) | Amido macrolides | |
| EP1171448A2 (en) | Macrolide antiinfective agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20011016 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |