JP2008530106A - ９−置換テトラサイクリン - Google Patents
９−置換テトラサイクリン Download PDFInfo
- Publication number
- JP2008530106A JP2008530106A JP2007555215A JP2007555215A JP2008530106A JP 2008530106 A JP2008530106 A JP 2008530106A JP 2007555215 A JP2007555215 A JP 2007555215A JP 2007555215 A JP2007555215 A JP 2007555215A JP 2008530106 A JP2008530106 A JP 2008530106A
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- optionally substituted
- alkyl
- substituted
- amino
- 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.)
- Pending
Links
- 239000004098 Tetracycline Substances 0.000 title claims description 51
- 229960002180 tetracycline Drugs 0.000 title claims description 43
- 235000019364 tetracycline Nutrition 0.000 title claims description 42
- 229930101283 tetracycline Natural products 0.000 title claims description 38
- 150000003522 tetracyclines Chemical class 0.000 title claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 136
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 35
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 30
- 150000002367 halogens Chemical class 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
- 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 18
- 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 21
- -1 furanyl compound Chemical class 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 18
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 12
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
- 229920002554 vinyl polymer Polymers 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229940040944 tetracyclines Drugs 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 claims description 4
- YPWZRSAWHVBHKT-HJYUBDRYSA-N C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CN(O)C(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O Chemical compound C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CN(O)C(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O YPWZRSAWHVBHKT-HJYUBDRYSA-N 0.000 claims description 3
- LEKRFUONRYATJQ-HJYUBDRYSA-N C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CNOC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O Chemical compound C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CNOC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O LEKRFUONRYATJQ-HJYUBDRYSA-N 0.000 claims description 3
- BWFPJHYJGVQIAK-IRBJOYOSSA-N C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(C=1SC=CC=1)C=C2NC(=O)CN1CCCCO1 Chemical compound C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(C=1SC=CC=1)C=C2NC(=O)CN1CCCCO1 BWFPJHYJGVQIAK-IRBJOYOSSA-N 0.000 claims description 3
- RXXSNMINZIRUMC-ISIOAQNYSA-N C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(I)C=C2NC(=O)CN1CCCCO1 Chemical compound C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(I)C=C2NC(=O)CN1CCCCO1 RXXSNMINZIRUMC-ISIOAQNYSA-N 0.000 claims description 3
- GBIOERKSNVSFTF-IRBJOYOSSA-N C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN(O)C1CCCCC1 Chemical compound C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN(O)C1CCCCC1 GBIOERKSNVSFTF-IRBJOYOSSA-N 0.000 claims description 3
- AOKMMNCWNFRPTP-XAGJCVETSA-N C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN(O)CC1=CC=CC=C1 Chemical compound C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN(O)CC1=CC=CC=C1 AOKMMNCWNFRPTP-XAGJCVETSA-N 0.000 claims description 3
- UTMNATNBZYCWRV-WOTXACPJSA-N C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN1CCCCO1 Chemical compound C([C@H]1C[C@H]2[C@@H](C(=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C1C(=O)C1=C2O)O)N(C)C)C1=C(N(C)C)C=C2NC(=O)CN1CCCCO1 UTMNATNBZYCWRV-WOTXACPJSA-N 0.000 claims description 3
- TZOYOTIAAROPSL-ISIOAQNYSA-N CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CN(C)OC)C(O)=C2C1=O Chemical compound CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CN(C)OC)C(O)=C2C1=O TZOYOTIAAROPSL-ISIOAQNYSA-N 0.000 claims description 3
- YSPKKPBDIDKKCZ-QFBSOPCBSA-N CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CN(O)C(C)C)C(O)=C2C1=O Chemical compound CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CN(O)C(C)C)C(O)=C2C1=O YSPKKPBDIDKKCZ-QFBSOPCBSA-N 0.000 claims description 3
- XJXCOWXBDNRXCB-NXHKEXIGSA-N CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CNOC)C(O)=C2C1=O Chemical compound CN(C)[C@@H]([C@@H]1C2)C(O)=C(C(N)=O)C(=O)[C@@]1(O)C(O)=C1[C@H]2CC2=C(N(C)C)C=C(NC(=O)CNOC)C(O)=C2C1=O XJXCOWXBDNRXCB-NXHKEXIGSA-N 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 4
- 125000001246 bromo group Chemical group Br* 0.000 claims 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims 3
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000003242 anti bacterial agent Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 229960004023 minocycline Drugs 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000191940 Staphylococcus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 0 CC(C)(C)ONCC(Nc1cc(N(C)C)c(C[C@@](C[C@@]([C@@](C(O)=C(C(*)=O)C2=O)N(C)C)[C@@]22O)(C(C3=O)=C2O)N)c3c1O)=O Chemical compound CC(C)(C)ONCC(Nc1cc(N(C)C)c(C[C@@](C[C@@]([C@@](C(O)=C(C(*)=O)C2=O)N(C)C)[C@@]22O)(C(C3=O)=C2O)N)c3c1O)=O 0.000 description 2
- 241000606790 Haemophilus Species 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 239000003814 drug Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- OZQGLZFAWYKKLQ-UHFFFAOYSA-N oxazinane Chemical compound C1CCONC1 OZQGLZFAWYKKLQ-UHFFFAOYSA-N 0.000 description 2
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 101150015970 tetM gene Proteins 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-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
- XHCNINMOALIGKM-UHFFFAOYSA-N 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetrazacyclotetradecane Chemical compound CC1CC(C)(C)NCCNC(C)CC(C)(C)NCCN1 XHCNINMOALIGKM-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- OYVRDNZTLBARSP-UHFFFAOYSA-N C1C2CC3=C(N(C)C)C=C(NC(=O)CBr)C(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O Chemical compound C1C2CC3=C(N(C)C)C=C(NC(=O)CBr)C(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O OYVRDNZTLBARSP-UHFFFAOYSA-N 0.000 description 1
- AXCOEPYIHDKZCQ-UHFFFAOYSA-N C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)(N(C)C)C(O)=C(C(N)=O)C2=O Chemical compound C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)(N(C)C)C(O)=C(C(N)=O)C2=O AXCOEPYIHDKZCQ-UHFFFAOYSA-N 0.000 description 1
- AUXSCKOXDVJNTQ-UHFFFAOYSA-N C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N)C(O)=C(C(N)=O)C2=O Chemical compound C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N)C(O)=C(C(N)=O)C2=O AUXSCKOXDVJNTQ-UHFFFAOYSA-N 0.000 description 1
- PRDSEJPYBPFVRD-UHFFFAOYSA-N CC(C)N1OCCC(C)C1 Chemical compound CC(C)N1OCCC(C)C1 PRDSEJPYBPFVRD-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000207202 Gardnerella Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- SSVAHXZUFFSFER-UHFFFAOYSA-N cyclohexyl(hydroxy)azanium;chloride Chemical compound Cl.ONC1CCCCC1 SSVAHXZUFFSFER-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([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
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- YSNXOQGDHGUKCZ-UHFFFAOYSA-N n-benzylhydroxylamine;hydron;chloride Chemical compound Cl.ONCC1=CC=CC=C1 YSNXOQGDHGUKCZ-UHFFFAOYSA-N 0.000 description 1
- ODHYIQOBTIWVRZ-UHFFFAOYSA-N n-propan-2-ylhydroxylamine Chemical compound CC(C)NO ODHYIQOBTIWVRZ-UHFFFAOYSA-N 0.000 description 1
- XWESXZZECGOXDQ-UHFFFAOYSA-N n-tert-butylhydroxylamine Chemical compound CC(C)(C)NO XWESXZZECGOXDQ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- KKVUFSINQFSJNK-UHFFFAOYSA-N o-tert-butylhydroxylamine Chemical compound CC(C)(C)ON KKVUFSINQFSJNK-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 101150045159 tetB gene Proteins 0.000 description 1
- 229940072172 tetracycline antibiotic Drugs 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- UKTDFYOZPFNQOQ-UHFFFAOYSA-N tributyl(thiophen-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CS1 UKTDFYOZPFNQOQ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/02—1,2-Oxazines; Hydrogenated 1,2-oxazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65326905P | 2005-02-15 | 2005-02-15 | |
| PCT/US2006/004562 WO2006088720A2 (en) | 2005-02-15 | 2006-02-09 | 9-substituted tetracyclines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008530106A true JP2008530106A (ja) | 2008-08-07 |
| JP2008530106A5 JP2008530106A5 (enExample) | 2009-02-05 |
Family
ID=36676182
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007555215A Pending JP2008530106A (ja) | 2005-02-15 | 2006-02-09 | ９−置換テトラサイクリン |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7812008B2 (enExample) |
| EP (1) | EP1848686A2 (enExample) |
| JP (1) | JP2008530106A (enExample) |
| CN (1) | CN101119964A (enExample) |
| AR (1) | AR053131A1 (enExample) |
| AU (1) | AU2006214543A1 (enExample) |
| BR (1) | BRPI0607353A2 (enExample) |
| CA (1) | CA2597870A1 (enExample) |
| GT (1) | GT200600063A (enExample) |
| MX (1) | MX2007009863A (enExample) |
| TW (1) | TW200640469A (enExample) |
| WO (1) | WO2006088720A2 (enExample) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013503196A (ja) * | 2009-08-28 | 2013-01-31 | テトラフェース ファーマシューティカルズ，インコーポレイテッド | テトラサイクリン化合物 |
| JP2015120723A (ja) * | 2008-08-08 | 2015-07-02 | テトラフェース ファーマシューティカルズ，インコーポレイテッド | Ｃ７−フルオロ置換テトラサイクリン化合物 |
| US9573895B2 (en) | 2012-08-31 | 2017-02-21 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| US10072007B2 (en) | 2009-05-08 | 2018-09-11 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| US10961190B2 (en) | 2016-10-19 | 2021-03-30 | Tetraphase Pharmaceuticals, Inc. | Crystalline forms of eravacycline |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2649221A1 (en) * | 2006-04-17 | 2007-10-25 | Evgeny Tsiperman | Isolation of tetracycline derivatives |
| US8198470B2 (en) * | 2006-04-24 | 2012-06-12 | Teva Pharmaceutical Industries Ltd. | Crystalline form II of tigecycline and processes for preparation thereof |
| DE202007019460U1 (de) * | 2006-04-24 | 2012-10-24 | Teva Pharmaceutical Industries Ltd. | Kristalline Tigecyclin-Formen |
| WO2008066935A2 (en) * | 2006-11-29 | 2008-06-05 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of tigecycline and processes for preparation thereof |
| WO2008066908A1 (en) * | 2006-11-30 | 2008-06-05 | Teva Pharmaceutical Industries Ltd. | Processes for preparation of 9-haloacetamidominocyclines |
| EP2114865A1 (en) * | 2007-03-01 | 2009-11-11 | Teva Pharmaceutical Industries Ltd. | Processes for purification of tigecycline |
| US7939513B2 (en) | 2007-09-07 | 2011-05-10 | Dr. Reddy's Laboratories Limited | Tetracycline derivatives as antibacterial agents |
| CN101955443B (zh) * | 2010-09-30 | 2012-05-23 | 浙江大学 | 一种替加环素中间体及其盐的制备方法 |
| WO2013013504A1 (zh) * | 2011-07-26 | 2013-01-31 | 山东亨利医药科技有限责任公司 | 替加环素衍生物 |
| CN107759503A (zh) * | 2016-08-16 | 2018-03-06 | 四川科伦博泰生物医药股份有限公司 | 一种四环素衍生物及其用途 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06199758A (ja) * | 1992-08-13 | 1994-07-19 | American Cyanamid Co | ９−［（置換グリシル）アミド］−６−デメチル−６−デオキシテトラサイクリン |
| JPH06206855A (ja) * | 1992-08-13 | 1994-07-26 | American Cyanamid Co | ７−（置換された）−９−［（置換されたグリシル）アミド］−６−デメチル−６−デオキシテトラサイクリン類 |
| JPH07309823A (ja) * | 1992-08-13 | 1995-11-28 | American Cyanamid Co | 新規な７−（置換された）−８−（置換された）−９−［（置換されたグリシル）アミド−６−デメチル−６−デオキシテトラサイクリン類 |
| JPH09501952A (ja) * | 1994-02-17 | 1997-02-25 | ファイザー インク． | ９−（置換アミノ）−アルファ−６−デオキシ−５−オキシテトラサイクリン誘導体、それらの製造及び、抗生物質としてのそれらの使用 |
| WO2002072532A1 (en) * | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7, 9-substituted tetracycline compounds |
| JP2004502750A (ja) * | 2000-07-07 | 2004-01-29 | トラスティーズ・オブ・タフツ・カレッジ | ７、８および９−置換テトラサイクリン化合物 |
| WO2004064728A2 (en) * | 2003-01-16 | 2004-08-05 | Paratek Pharmaceuticals, Inc. | Use of specific tetracycline compounds in therapy |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2482055A (en) | 1948-02-11 | 1949-09-13 | American Cyanamid Co | Aureomycin and preparation of same |
| US3007965A (en) | 1959-02-13 | 1961-11-07 | American Cyanamid Co | New tetracyclines produced by streptomyces aureofaciens |
| US3043875A (en) | 1959-10-22 | 1962-07-10 | Pfizer & Co C | Halogenated tetracycline derivatives and processes for their preparation |
| FR1430859A (enExample) | 1960-05-23 | 1966-05-25 | ||
| US3338963A (en) | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
| US3148212A (en) | 1961-12-22 | 1964-09-08 | American Cyanamid Co | Reductive alkylation process |
| US3360557A (en) | 1963-05-10 | 1967-12-26 | American Cyanamid Co | 9-hydroxytetracyclines and a process of preparing same |
| USRE26253E (en) | 1963-05-17 | 1967-08-15 | And z-alkylamino-g-deoxytetracycline | |
| US3341585A (en) | 1966-05-06 | 1967-09-12 | American Cyanamid Co | Substituted 7-and/or 9-amino-6-deoxytetracyclines |
| US3360561A (en) | 1967-06-19 | 1967-12-26 | American Cyanamid Co | Nitration of tetracyclines |
| US3518306A (en) | 1968-02-19 | 1970-06-30 | American Cyanamid Co | 7- and/or 9-(n-nitrosoalkylamino)-6-demethyl-6-deoxytetracyclines |
| US4806529A (en) | 1982-11-18 | 1989-02-21 | Trustees Of Tufts College, Tufts University | Tetracycline activity enhancement |
| US5494903A (en) | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
-
2006
- 2006-02-09 MX MX2007009863A patent/MX2007009863A/es active IP Right Grant
- 2006-02-09 JP JP2007555215A patent/JP2008530106A/ja active Pending
- 2006-02-09 CA CA002597870A patent/CA2597870A1/en not_active Abandoned
- 2006-02-09 CN CNA2006800049045A patent/CN101119964A/zh active Pending
- 2006-02-09 AU AU2006214543A patent/AU2006214543A1/en not_active Abandoned
- 2006-02-09 BR BRPI0607353-0A patent/BRPI0607353A2/pt not_active IP Right Cessation
- 2006-02-09 EP EP06720553A patent/EP1848686A2/en not_active Withdrawn
- 2006-02-09 WO PCT/US2006/004562 patent/WO2006088720A2/en not_active Ceased
- 2006-02-14 GT GT200600063A patent/GT200600063A/es unknown
- 2006-02-14 TW TW095104895A patent/TW200640469A/zh unknown
- 2006-02-14 AR ARP060100514A patent/AR053131A1/es not_active Application Discontinuation
- 2006-02-14 US US11/354,306 patent/US7812008B2/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06199758A (ja) * | 1992-08-13 | 1994-07-19 | American Cyanamid Co | ９−［（置換グリシル）アミド］−６−デメチル−６−デオキシテトラサイクリン |
| JPH06206855A (ja) * | 1992-08-13 | 1994-07-26 | American Cyanamid Co | ７−（置換された）−９−［（置換されたグリシル）アミド］−６−デメチル−６−デオキシテトラサイクリン類 |
| JPH07309823A (ja) * | 1992-08-13 | 1995-11-28 | American Cyanamid Co | 新規な７−（置換された）−８−（置換された）−９−［（置換されたグリシル）アミド−６−デメチル−６−デオキシテトラサイクリン類 |
| JPH09501952A (ja) * | 1994-02-17 | 1997-02-25 | ファイザー インク． | ９−（置換アミノ）−アルファ−６−デオキシ−５−オキシテトラサイクリン誘導体、それらの製造及び、抗生物質としてのそれらの使用 |
| JP2004502750A (ja) * | 2000-07-07 | 2004-01-29 | トラスティーズ・オブ・タフツ・カレッジ | ７、８および９−置換テトラサイクリン化合物 |
| WO2002072532A1 (en) * | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7, 9-substituted tetracycline compounds |
| WO2004064728A2 (en) * | 2003-01-16 | 2004-08-05 | Paratek Pharmaceuticals, Inc. | Use of specific tetracycline compounds in therapy |
Non-Patent Citations (1)
| Title |
|---|
| JPN5007026344; ＳＵＭ，Ｐ-Ｅ． ａｎｄ ＰＥＴＥＲＳＥＮ，Ｐ．: 'Ｓｙｎｔｈｅｓｉｓ ａｎｄ ｓｔｒｕｃｔｕｒｅ-ａｃｔｉｖｉｔｙ ｒｅｌａｔｉｏｎｓｈｉｐ ｏｆ ｎｏｖｅｌ ｇｌｙｃｙｌｃｙｃｌｉｎｅ ｄｅｒｉｖａｔｉｖｅｓ ｌｅａｄｉｎｇ ｔｏ ｔｈｅ ｄｉｓｃ' ＢＩＯＯＲＧＡＮＩＣ ＆ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ ＬＥＴＴＥＲＳ Ｖ９ Ｎ１０, 19990517, Ｐ１４５９-１４６２ * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015120723A (ja) * | 2008-08-08 | 2015-07-02 | テトラフェース ファーマシューティカルズ，インコーポレイテッド | Ｃ７−フルオロ置換テトラサイクリン化合物 |
| US10072007B2 (en) | 2009-05-08 | 2018-09-11 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| JP2013503196A (ja) * | 2009-08-28 | 2013-01-31 | テトラフェース ファーマシューティカルズ，インコーポレイテッド | テトラサイクリン化合物 |
| JP2016130243A (ja) * | 2009-08-28 | 2016-07-21 | テトラフェース ファーマシューティカルズ，インコーポレイテッド | テトラサイクリン化合物 |
| US9624166B2 (en) | 2009-08-28 | 2017-04-18 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| US9573895B2 (en) | 2012-08-31 | 2017-02-21 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| US10315992B2 (en) | 2012-08-31 | 2019-06-11 | Tetraphase Pharmaceuticals, Inc. | Tetracyline compounds |
| US10913712B2 (en) | 2012-08-31 | 2021-02-09 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| US10961190B2 (en) | 2016-10-19 | 2021-03-30 | Tetraphase Pharmaceuticals, Inc. | Crystalline forms of eravacycline |
| US11578044B2 (en) | 2016-10-19 | 2023-02-14 | Tetraphase Pharmaceuticals, Inc. | Crystalline forms of eravacycline |
| US12269807B2 (en) | 2016-10-19 | 2025-04-08 | Tetraphase Pharmaceuticals, Inc. | Crystalline forms of eravacycline |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0607353A2 (pt) | 2009-09-01 |
| WO2006088720A2 (en) | 2006-08-24 |
| MX2007009863A (es) | 2007-09-04 |
| GT200600063A (es) | 2006-11-09 |
| AR053131A1 (es) | 2007-04-25 |
| US20060183720A1 (en) | 2006-08-17 |
| WO2006088720A3 (en) | 2007-01-11 |
| TW200640469A (en) | 2006-12-01 |
| EP1848686A2 (en) | 2007-10-31 |
| CA2597870A1 (en) | 2006-08-24 |
| CN101119964A (zh) | 2008-02-06 |
| US7812008B2 (en) | 2010-10-12 |
| AU2006214543A1 (en) | 2006-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0535346B1 (en) | 9-amino-7-substituted-6-demethyl-6-deoxytetracyclines | |
| JP3186863B2 (ja) | ７−置換−９−置換アミノ−６−デメチル−６−デオキシテトラサイクリン | |
| US20130029943A1 (en) | Methods of Preparing Substituted Tetracyclines with Transition Metal-Based Chemistries | |
| JP2008530106A (ja) | ９−置換テトラサイクリン | |
| US20080177080A1 (en) | Oxazole derivatives of tetracyclines | |
| JP2004502752A (ja) | ９−置換ミノサイクリン化合物 | |
| BRPI0720569B1 (pt) | compostos de tetraciclina substituída e uso dos ditos compostos para o tratamento de uma infecção bacteriana, viral ou parasitária | |
| CZ159993A3 (en) | 7-(substituted)-9-£(substituted glycyl)amido|-6-demethyl-6-deoxytetracyclines, and process of their preparation | |
| CA3071155A1 (en) | Cystobactamide derivatives | |
| KR20080041722A (ko) | 글리실사이클린의 9-아미노카르보닐 치환된 유도체 | |
| TW548257B (en) | Methods of preparing substituted tetracyclines with transition metal-based chemistries | |
| HK1000319B (en) | 9-amino-7-substituted-6-demethyl-6-deoxytetracyclines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081210 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081210 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20100713 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20100715 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20110914 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110926 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111219 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20111219 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120827 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130422 |