TWI262181B - Florfenicol prodrug having improved water solubility - Google Patents
Florfenicol prodrug having improved water solubility Download PDFInfo
- Publication number
- TWI262181B TWI262181B TW093139689A TW93139689A TWI262181B TW I262181 B TWI262181 B TW I262181B TW 093139689 A TW093139689 A TW 093139689A TW 93139689 A TW93139689 A TW 93139689A TW I262181 B TWI262181 B TW I262181B
- Authority
- TW
- Taiwan
- Prior art keywords
- alkyl
- group
- phosphate
- chloramphenicol
- acid
- Prior art date
Links
- 239000000651 prodrug Substances 0.000 title claims abstract description 47
- 229940002612 prodrug Drugs 0.000 title claims abstract description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title abstract description 20
- AYIRNRDRBQJXIF-NXEZZACHSA-N (-)-Florfenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CF)NC(=O)C(Cl)Cl)C=C1 AYIRNRDRBQJXIF-NXEZZACHSA-N 0.000 title abstract description 6
- 229960003760 florfenicol Drugs 0.000 title abstract 3
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 68
- 229960005091 chloramphenicol Drugs 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 52
- 229910019142 PO4 Inorganic materials 0.000 claims description 50
- 235000021317 phosphate Nutrition 0.000 claims description 50
- 239000010452 phosphate Substances 0.000 claims description 48
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 44
- -1 fluoromethanesulfonyl Chemical group 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 150000001768 cations Chemical class 0.000 claims description 23
- 239000007864 aqueous solution Substances 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 241000238366 Cephalopoda Species 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- XHKUTQNVGAHLPK-UHFFFAOYSA-N 2-fluorocyclohexa-2,5-diene-1,4-dione Chemical compound FC1=CC(=O)C=CC1=O XHKUTQNVGAHLPK-UHFFFAOYSA-N 0.000 claims description 9
- 239000007789 gas Substances 0.000 claims description 9
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 claims description 8
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000010436 fluorite Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
- UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 7
- 208000035143 Bacterial infection Diseases 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229930188189 sulfomycin Natural products 0.000 claims description 5
- 108010051634 sulfomycin Proteins 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 229960005274 benzocaine Drugs 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 241000894007 species Species 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 150000004985 diamines Chemical class 0.000 claims description 3
- HGFAGBHAGYXJKZ-UHFFFAOYSA-N fluoromethanesulfonamide Chemical compound NS(=O)(=O)CF HGFAGBHAGYXJKZ-UHFFFAOYSA-N 0.000 claims description 3
- BTZNPZMHENLISZ-UHFFFAOYSA-M fluoromethanesulfonate Chemical compound [O-]S(=O)(=O)CF BTZNPZMHENLISZ-UHFFFAOYSA-M 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 3
- 229960004919 procaine Drugs 0.000 claims description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229960003194 meglumine Drugs 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000004575 stone Substances 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 1
- 239000005944 Chlorpyrifos Substances 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims 1
- 241000555745 Sciuridae Species 0.000 claims 1
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical compound CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 claims 1
- 210000004709 eyebrow Anatomy 0.000 claims 1
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 claims 1
- 229960003160 hyaluronic acid Drugs 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 229910052707 ruthenium Inorganic materials 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- USPTVMVRNZEXCP-UHFFFAOYSA-N sulfamoyl fluoride Chemical compound NS(F)(=O)=O USPTVMVRNZEXCP-UHFFFAOYSA-N 0.000 claims 1
- 125000004149 thio group Chemical group *S* 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 16
- 238000001727 in vivo Methods 0.000 abstract description 3
- 150000003014 phosphoric acid esters Chemical class 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 24
- 241000269817 Centrarchidae Species 0.000 description 12
- 150000002500 ions Chemical class 0.000 description 12
- 239000000052 vinegar Substances 0.000 description 9
- 235000021419 vinegar Nutrition 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 235000019688 fish Nutrition 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 206010036790 Productive cough Diseases 0.000 description 7
- 241000282887 Suidae Species 0.000 description 7
- 244000309466 calf Species 0.000 description 7
- 210000003802 sputum Anatomy 0.000 description 7
- 208000024794 sputum Diseases 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 241000251468 Actinopterygii Species 0.000 description 5
- 241000972773 Aulopiformes Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 241000239226 Scorpiones Species 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 235000019515 salmon Nutrition 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 229930002875 chlorophyll Natural products 0.000 description 4
- 235000019804 chlorophyll Nutrition 0.000 description 4
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 241000272517 Anseriformes Species 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 241000276616 Cichlidae Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000283073 Equus caballus Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000408747 Lepomis gibbosus Species 0.000 description 3
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 3
- 101800000989 Oxytocin Proteins 0.000 description 3
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- BTZNPZMHENLISZ-UHFFFAOYSA-N fluoromethanesulfonic acid Chemical compound OS(=O)(=O)CF BTZNPZMHENLISZ-UHFFFAOYSA-N 0.000 description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 229960001723 oxytocin Drugs 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- ROWKJAVDOGWPAT-UHFFFAOYSA-N Acetoin Chemical compound CC(O)C(C)=O ROWKJAVDOGWPAT-UHFFFAOYSA-N 0.000 description 2
- 241001559555 Ambloplites rupestris Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241001085763 Centropristis striata Species 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- 241000611752 Coregonus clupeaformis Species 0.000 description 2
- 241001155417 Enneacanthus gloriosus Species 0.000 description 2
- 241001656472 Epinephelus morio Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000947653 Fontinalis Species 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 241000442132 Lactarius lactarius Species 0.000 description 2
- 241000489982 Lagodon rhomboides Species 0.000 description 2
- 241001155442 Lepomis cyanellus Species 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000277326 Oncorhynchus gorbuscha Species 0.000 description 2
- 241000277275 Oncorhynchus mykiss Species 0.000 description 2
- 241000277277 Oncorhynchus nerka Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000277288 Salmo trutta Species 0.000 description 2
- 241000277297 Salvelinus leucomaenis Species 0.000 description 2
- 241000207929 Scutellaria Species 0.000 description 2
- 241001417495 Serranidae Species 0.000 description 2
- 241000675916 Serranus phoebe Species 0.000 description 2
- 241000276707 Tilapia Species 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 229960002464 fluoxetine Drugs 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- YWILDZMVBIMXID-KGHBUBBXSA-N (4s,4as,5as,6s,12ar)-n-[[4-[n-(diaminomethylidene)carbamimidoyl]piperazin-1-yl]methyl]-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;dihydrochloride Chemical class Cl.Cl.OC([C@@]1(O)C(=O)C=2[C@@H]([C@](C3=CC=CC(O)=C3C=2O)(C)O)C[C@H]1[C@@H](C1=O)N(C)C)=C1C(=O)NCN1CCN(C(=N)N=C(N)N)CC1 YWILDZMVBIMXID-KGHBUBBXSA-N 0.000 description 1
- 150000004345 1,2-dihydroxyanthraquinones Chemical class 0.000 description 1
- VIESAWGOYVNHLV-UHFFFAOYSA-N 1,3-dihydropyrrol-2-one Chemical compound O=C1CC=CN1 VIESAWGOYVNHLV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- FTMJFHVKAXPFIY-RKDXNWHRSA-N 2,2-dichloro-n-[(1r,2r)-1,3-dihydroxy-1-(3-nitrophenyl)propan-2-yl]acetamide Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=CC([N+]([O-])=O)=C1 FTMJFHVKAXPFIY-RKDXNWHRSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-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
- 241001519451 Abramis brama Species 0.000 description 1
- 241001609368 Acamptopappus Species 0.000 description 1
- OYMZTORLGBISLR-UHFFFAOYSA-N Acetomycin Natural products CC1C(OC(C)=O)OC(=O)C1(C)C(C)=O OYMZTORLGBISLR-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000606748 Actinobacillus pleuropneumoniae Species 0.000 description 1
- 241000607525 Aeromonas salmonicida Species 0.000 description 1
- 241001580935 Aglossa pinguinalis Species 0.000 description 1
- 241000219498 Alnus glutinosa Species 0.000 description 1
- 241000705529 Andinoacara pulcher Species 0.000 description 1
- 241000264349 Archosargus probatocephalus Species 0.000 description 1
- 241000473391 Archosargus rhomboidalis Species 0.000 description 1
- 240000005528 Arctium lappa Species 0.000 description 1
- 235000003130 Arctium lappa Nutrition 0.000 description 1
- 235000008078 Arctium minus Nutrition 0.000 description 1
- 235000000832 Ayote Nutrition 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 241000889236 Calamus penna Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920002160 Celluloid Polymers 0.000 description 1
- 241001155433 Centrarchus macropterus Species 0.000 description 1
- 241000758604 Centropristis ocyurus Species 0.000 description 1
- 241000758603 Centropristis philadelphica Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241001155440 Chaenobryttus gulosus Species 0.000 description 1
- 241000272470 Circus Species 0.000 description 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 description 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 description 1
- 235000009685 Crataegus X maligna Nutrition 0.000 description 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 description 1
- 235000009486 Crataegus bullatus Nutrition 0.000 description 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 description 1
- 235000009682 Crataegus limnophila Nutrition 0.000 description 1
- 235000004423 Crataegus monogyna Nutrition 0.000 description 1
- 240000000171 Crataegus monogyna Species 0.000 description 1
- 235000002313 Crataegus paludosa Nutrition 0.000 description 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 description 1
- 241000320737 Crenicichla lacustris Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 240000004244 Cucurbita moschata Species 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 241001020588 Diplectrum bivittatum Species 0.000 description 1
- 241000275449 Diplectrum formosum Species 0.000 description 1
- 241000949274 Edwardsiella ictaluri Species 0.000 description 1
- 241001236173 Elassoma okefenokee Species 0.000 description 1
- 241001236171 Elassoma zonatum Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241001236158 Enneacanthus Species 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010016761 Flat chest Diseases 0.000 description 1
- 241000605952 Fusobacterium necrophorum Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000545744 Hirudinea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000321408 Hyporthodus flavolimbatus Species 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000721656 Lepomis Species 0.000 description 1
- 241001155465 Lepomis auritus Species 0.000 description 1
- 241000721654 Lepomis macrochirus Species 0.000 description 1
- 241000408783 Lepomis megalotis Species 0.000 description 1
- 241000772413 Lutrogale perspicillata Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000290125 Micropterus coosae Species 0.000 description 1
- 241001328758 Micropterus dolomieu Species 0.000 description 1
- 241000290127 Micropterus punctulatus Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241001417899 Oncorhynchus clarkii Species 0.000 description 1
- 241000277329 Oncorhynchus keta Species 0.000 description 1
- 241000277338 Oncorhynchus kisutch Species 0.000 description 1
- 241000277269 Oncorhynchus masou Species 0.000 description 1
- 241001280377 Oncorhynchus tshawytscha Species 0.000 description 1
- 241000276719 Oreochromis Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 244000170916 Paeonia officinalis Species 0.000 description 1
- 235000006484 Paeonia officinalis Nutrition 0.000 description 1
- 241001282110 Pagrus major Species 0.000 description 1
- 241001396961 Parapristipoma trilineatum Species 0.000 description 1
- 241000606856 Pasteurella multocida Species 0.000 description 1
- 241001247287 Pentalinon luteum Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001155420 Pomoxis annularis Species 0.000 description 1
- 241000269816 Pomoxis nigromaculatus Species 0.000 description 1
- 241001135223 Prevotella melaninogenica Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000767458 Prosopium cylindraceum Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 240000004350 Prunus spinosa Species 0.000 description 1
- 235000010829 Prunus spinosa Nutrition 0.000 description 1
- 241001260334 Pterophyllum scalare Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 240000005578 Rivina humilis Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000277263 Salmo Species 0.000 description 1
- 241000277289 Salmo salar Species 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 241000276677 Sarotherodon Species 0.000 description 1
- 241001417494 Sciaenidae Species 0.000 description 1
- 241001290266 Sciaenops ocellatus Species 0.000 description 1
- 241001282153 Scopelogadus mizolepis Species 0.000 description 1
- 241001521797 Scorpaena notata Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000287219 Serinus canaria Species 0.000 description 1
- 241000347374 Serranus Species 0.000 description 1
- 241000675264 Serranus tortugarum Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 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
- 241000269788 Sparidae Species 0.000 description 1
- 241000269808 Sparus Species 0.000 description 1
- 241000063156 Squatina squatina Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241001494108 Stenotomus Species 0.000 description 1
- 241001494106 Stenotomus chrysops Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000271567 Struthioniformes Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 241000270666 Testudines Species 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- HRVQDBZKORPEPG-UHFFFAOYSA-N [F].COS(O)(=O)=O Chemical compound [F].COS(O)(=O)=O HRVQDBZKORPEPG-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- OYMZTORLGBISLR-RHFNHBFPSA-N acetomycin Chemical compound C[C@@H]1[C@H](OC(C)=O)OC(=O)[C@]1(C)C(C)=O OYMZTORLGBISLR-RHFNHBFPSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- CJFCGSLFEZPBNJ-UHFFFAOYSA-N carbamimidoylazanium;phosphate Chemical compound NC([NH3+])=N.NC([NH3+])=N.NC([NH3+])=N.[O-]P([O-])([O-])=O CJFCGSLFEZPBNJ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 description 1
- 229910001919 chlorite Inorganic materials 0.000 description 1
- 229910052619 chlorite group Inorganic materials 0.000 description 1
- HCXRJZPKQRLSCW-UHFFFAOYSA-N chloroform;sulfuric acid Chemical compound ClC(Cl)Cl.OS(O)(=O)=O HCXRJZPKQRLSCW-UHFFFAOYSA-N 0.000 description 1
- QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 208000028104 epidemic louse-borne typhus Diseases 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- GINFBXXYGUODAT-UHFFFAOYSA-N flucarbazone Chemical compound O=C1N(C)C(OC)=NN1C(=O)NS(=O)(=O)C1=CC=CC=C1OC(F)(F)F GINFBXXYGUODAT-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- NBVXSUQYWXRMNV-OUBTZVSYSA-N fluoromethane Chemical class F[13CH3] NBVXSUQYWXRMNV-OUBTZVSYSA-N 0.000 description 1
- VSAVIUSEFTYPSF-UHFFFAOYSA-N fluoromethanesulfinic acid Chemical compound OS(=O)CF VSAVIUSEFTYPSF-UHFFFAOYSA-N 0.000 description 1
- NNINWAWDVUHMGM-UHFFFAOYSA-N fluoromethanesulfonyl chloride Chemical compound FCS(Cl)(=O)=O NNINWAWDVUHMGM-UHFFFAOYSA-N 0.000 description 1
- AIUYAMGZOLZABQ-PMYHJQRFSA-N fluoromycin Chemical compound O([C@H]1[C@@H]([C@H](O)[C@H](N)[C@H](C)O1)O)C(C(O)C=1SC=C(N=1)C=1SC(=CN=1)C(=O)NCCCCNC(=S)NC=1C=C2C(C3(C4=CC=C(O)C=C4OC4=CC(O)=CC=C43)OC2=O)=CC=1)NC(=O)C(C(O)C)NC(=O)CC(O)C(C)NC(=O)C(C(O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C AIUYAMGZOLZABQ-PMYHJQRFSA-N 0.000 description 1
- 108700007815 fluoromycin Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- GFAZHVHNLUBROE-UHFFFAOYSA-N hydroxymethyl propionaldehyde Natural products CCC(=O)CO GFAZHVHNLUBROE-UHFFFAOYSA-N 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical class CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 150000002773 monoterpene derivatives Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229940060568 nuflor Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000000467 phytic acid Substances 0.000 description 1
- 229940068041 phytic acid Drugs 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- 235000020236 pumpkin seed Nutrition 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000003535 tetraterpenes Chemical class 0.000 description 1
- 235000009657 tetraterpenes Nutrition 0.000 description 1
- JOPDZQBPOWAEHC-UHFFFAOYSA-H tristrontium;diphosphate Chemical compound [Sr+2].[Sr+2].[Sr+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O JOPDZQBPOWAEHC-UHFFFAOYSA-H 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 206010061393 typhus Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/094—Esters of phosphoric acids with arylalkanols
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53222703P | 2003-12-23 | 2003-12-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200533640A TW200533640A (en) | 2005-10-16 |
| TWI262181B true TWI262181B (en) | 2006-09-21 |
Family
ID=34738768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW093139689A TWI262181B (en) | 2003-12-23 | 2004-12-20 | Florfenicol prodrug having improved water solubility |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US7153842B2 (https=) |
| EP (1) | EP1696934B1 (https=) |
| JP (2) | JP4719160B2 (https=) |
| KR (1) | KR20060111605A (https=) |
| CN (1) | CN100579532C (https=) |
| AR (1) | AR046970A1 (https=) |
| BR (1) | BRPI0418133A2 (https=) |
| CA (1) | CA2550660C (https=) |
| EC (1) | ECSP066670A (https=) |
| IL (2) | IL176342A (https=) |
| MX (1) | MXPA06007215A (https=) |
| NO (1) | NO20063244L (https=) |
| NZ (1) | NZ547592A (https=) |
| PE (1) | PE20050822A1 (https=) |
| RU (1) | RU2006126519A (https=) |
| TW (1) | TWI262181B (https=) |
| WO (1) | WO2005063257A1 (https=) |
| ZA (1) | ZA200605165B (https=) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200505425A (en) | 2003-05-29 | 2005-02-16 | Schering Plough Ltd | Compositions and method for treating infection in cattle and swine |
| US7439268B2 (en) | 2003-07-18 | 2008-10-21 | Idexx Laboratories | Compositions containing prodrugs of florfenicol and methods of use |
| CA2550660C (en) * | 2003-12-23 | 2011-03-15 | Schering-Plough Ltd. | Florfenicol prodrug having improved water solubility |
| US7361689B2 (en) * | 2003-12-31 | 2008-04-22 | Schering-Plough Animal Health Corporation | Antibacterial 1-(4-mono- and di-halomethylsulphonylphenyl)-2-acylamino-3-fluoroproponals and preparation thereof |
| BRPI0515917A (pt) | 2004-09-23 | 2008-08-12 | Schering Plough Ltd | controle de parasitas em animais pelo uso de novos derivados de éter de oxima de trifluorometanossulfonanilida |
| EP1811841B1 (en) | 2004-11-19 | 2009-10-28 | Schering-Plough Ltd. | Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1h-pyrrol-2-yl) acrylonitrile derivatives |
| WO2006135648A2 (en) * | 2005-06-09 | 2006-12-21 | Schering-Plough Ltd. | Control of parasites in animals by n-[(phenyloxy)phenyl]-1,1,1-trifluoromethanesulfonamide and n-[(phenylsulfanyl)phenyl]-1,1,1-trifluoromethanesulfonamide derivatives |
| US8119667B2 (en) * | 2005-12-29 | 2012-02-21 | Schering-Plough Animal Health Corporation | Carbonates of fenicol antibiotics |
| WO2008076259A1 (en) | 2006-12-13 | 2008-06-26 | Schering-Plough Ltd. | Water-soluble prodrugs of florfenicol and its analogs |
| CN101600422A (zh) * | 2006-12-13 | 2009-12-09 | 先灵-普劳有限公司 | 在亲脂性溶媒系统中的水溶性苯丙醇前药 |
| CA2672795A1 (en) * | 2006-12-13 | 2008-06-26 | Schering-Plough Ltd. | Water-soluble prodrugs of chloramphenicol, thiamphenicol, and analogs thereof |
| TWI430995B (zh) | 2007-06-26 | 2014-03-21 | Du Pont | 萘異唑啉無脊椎有害動物控制劑 |
| KR101769728B1 (ko) | 2007-06-27 | 2017-08-18 | 이 아이 듀폰 디 네모아 앤드 캄파니 | 동물 해충 방제 방법 |
| PE20091171A1 (es) * | 2007-12-14 | 2009-08-03 | Schering Plough Ltd | Proceso para recuperar florfenicol y analogos de florfenicol |
| WO2010014566A2 (en) * | 2008-07-30 | 2010-02-04 | Intervet International B.V. | Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol |
| UA110924C2 (uk) | 2009-08-05 | 2016-03-10 | Е. І. Дю Пон Де Немур Енд Компані | Мезоіонні пестициди |
| US20120122680A1 (en) | 2009-08-05 | 2012-05-17 | E.I. Du Pont De Nemours And Company | Mesoionic pesticides |
| KR20120050467A (ko) | 2009-08-05 | 2012-05-18 | 이 아이 듀폰 디 네모아 앤드 캄파니 | 메소이온성 살충제 |
| WO2012087630A1 (en) | 2010-12-20 | 2012-06-28 | E.I. Du Pont De Nemours And Company | Pyridine and pyrimidine compounds for controlling invertebrate |
| WO2012150520A1 (en) | 2011-05-02 | 2012-11-08 | Pfizer Inc. | Novel cephalosporins useful as antibacterial agents |
| JP2014520151A (ja) | 2011-06-20 | 2014-08-21 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー | 蠕虫感染を処置するためのヘテロ環式化合物 |
| TW201326128A (zh) | 2011-11-28 | 2013-07-01 | Du Pont | 磺醯胺驅蟲劑 |
| WO2013158422A1 (en) | 2012-04-17 | 2013-10-24 | E. I. Du Pont De Nemours And Company | Heterocyclic compounds for controlling invertebrate pests |
| WO2014099837A1 (en) | 2012-12-18 | 2014-06-26 | E. I. Du Pont De Nemours And Company | Sulfonamide anthelmintics |
| CN103242363B (zh) * | 2013-04-18 | 2015-10-28 | 湖北龙翔药业有限公司 | 氟苯尼考磷酸二酯及盐及其制备方法 |
| CN103923118A (zh) * | 2014-04-08 | 2014-07-16 | 张家港威胜生物医药有限公司 | 一种水溶性氟苯尼考衍生物的合成方法 |
| CN105111234B (zh) * | 2015-09-23 | 2017-05-17 | 河北远征禾木药业有限公司 | 一种氟苯尼考磷酸酯的合成方法 |
| CN110078729A (zh) * | 2019-06-11 | 2019-08-02 | 石家庄学院 | 一种水溶性氟苯尼考前药及其制备方法 |
| CN115286544A (zh) * | 2022-10-08 | 2022-11-04 | 世华合创生物技术开发(山东)有限公司 | 一种氟苯尼考衍生物、制备方法及其在抗细菌感染的应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2776992A (en) * | 1956-03-14 | 1957-01-08 | Du Pont | Trifluoromethylsulfonylphenyldichloracetamidopropandiol |
| US4235892A (en) * | 1979-02-05 | 1980-11-25 | Schering Corporation, Patent Dept. | 1-Aryl-2-acylamido-3-fluoro-1-propanols, methods for their use as antibacterial agents and compositions useful therefor |
| FR2562543B1 (fr) * | 1984-04-10 | 1987-09-25 | Elf Aquitaine | Nouveaux phosphonites cycliques, leur preparation et applications |
| US5352832A (en) * | 1992-12-18 | 1994-10-04 | Schering Corporation | Asymmetric process for preparing florfenicol, thiamphenicol chloramphenicol and oxazoline intermediates |
| US6864240B1 (en) * | 1999-06-15 | 2005-03-08 | Elan Pharmaceuticals, Inc. | Dipeptide inhibitors of β-secretase |
| US6670344B2 (en) | 2000-09-14 | 2003-12-30 | Bristol-Myers Squibb Company | Combretastatin A-4 phosphate prodrug mono- and di-organic amine salts, mono- and di- amino acid salts, and mono- and di-amino acid ester salts |
| US7547686B2 (en) | 2001-06-15 | 2009-06-16 | Arizona Board of Regents, a body corporate of the State of Arizona, Acting for and on Behalf of the Arizona State University | Combretastatin A-3 prodrug |
| CN1649829A (zh) * | 2002-03-08 | 2005-08-03 | 先灵-普劳有限公司 | 新型氟苯尼考类抗生素 |
| US7439268B2 (en) * | 2003-07-18 | 2008-10-21 | Idexx Laboratories | Compositions containing prodrugs of florfenicol and methods of use |
| CA2550660C (en) | 2003-12-23 | 2011-03-15 | Schering-Plough Ltd. | Florfenicol prodrug having improved water solubility |
| US7361689B2 (en) | 2003-12-31 | 2008-04-22 | Schering-Plough Animal Health Corporation | Antibacterial 1-(4-mono- and di-halomethylsulphonylphenyl)-2-acylamino-3-fluoroproponals and preparation thereof |
-
2004
- 2004-12-20 CA CA2550660A patent/CA2550660C/en not_active Expired - Fee Related
- 2004-12-20 CN CN200480038867A patent/CN100579532C/zh not_active Expired - Lifetime
- 2004-12-20 KR KR1020067012460A patent/KR20060111605A/ko not_active Withdrawn
- 2004-12-20 MX MXPA06007215A patent/MXPA06007215A/es active IP Right Grant
- 2004-12-20 TW TW093139689A patent/TWI262181B/zh not_active IP Right Cessation
- 2004-12-20 WO PCT/US2004/042591 patent/WO2005063257A1/en not_active Ceased
- 2004-12-20 BR BRPI0418133-6A patent/BRPI0418133A2/pt not_active IP Right Cessation
- 2004-12-20 US US11/016,794 patent/US7153842B2/en not_active Expired - Lifetime
- 2004-12-20 JP JP2006547183A patent/JP4719160B2/ja not_active Expired - Fee Related
- 2004-12-20 EP EP04814736.7A patent/EP1696934B1/en not_active Expired - Lifetime
- 2004-12-20 NZ NZ547592A patent/NZ547592A/xx not_active IP Right Cessation
- 2004-12-20 RU RU2006126519/04A patent/RU2006126519A/ru not_active Application Discontinuation
- 2004-12-20 AR ARP040104805A patent/AR046970A1/es not_active Application Discontinuation
-
2005
- 2005-01-03 PE PE2005000020A patent/PE20050822A1/es not_active Application Discontinuation
-
2006
- 2006-06-15 IL IL176342A patent/IL176342A/en not_active IP Right Cessation
- 2006-06-22 EC EC2006006670A patent/ECSP066670A/es unknown
- 2006-06-22 ZA ZA200605165A patent/ZA200605165B/xx unknown
- 2006-07-12 NO NO20063244A patent/NO20063244L/no not_active Application Discontinuation
- 2006-08-29 US US11/511,810 patent/US7572777B2/en not_active Expired - Lifetime
-
2009
- 2009-07-23 IL IL200041A patent/IL200041A0/en unknown
-
2011
- 2011-02-23 JP JP2011037689A patent/JP2011148804A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007516286A (ja) | 2007-06-21 |
| MXPA06007215A (es) | 2006-08-18 |
| AU2004308913A1 (en) | 2005-07-14 |
| US7572777B2 (en) | 2009-08-11 |
| NO20063244L (no) | 2006-09-20 |
| CN100579532C (zh) | 2010-01-13 |
| AR046970A1 (es) | 2006-01-04 |
| IL176342A0 (en) | 2006-10-05 |
| ECSP066670A (es) | 2006-10-25 |
| EP1696934A1 (en) | 2006-09-06 |
| IL176342A (en) | 2011-08-31 |
| IL200041A0 (en) | 2010-04-15 |
| RU2006126519A (ru) | 2008-01-27 |
| PE20050822A1 (es) | 2005-10-01 |
| CA2550660A1 (en) | 2005-07-14 |
| TW200533640A (en) | 2005-10-16 |
| CA2550660C (en) | 2011-03-15 |
| JP4719160B2 (ja) | 2011-07-06 |
| NZ547592A (en) | 2009-07-31 |
| US20070021387A1 (en) | 2007-01-25 |
| CN1897954A (zh) | 2007-01-17 |
| US7153842B2 (en) | 2006-12-26 |
| ZA200605165B (en) | 2007-12-27 |
| KR20060111605A (ko) | 2006-10-27 |
| EP1696934B1 (en) | 2013-05-29 |
| JP2011148804A (ja) | 2011-08-04 |
| US20050182031A1 (en) | 2005-08-18 |
| BRPI0418133A2 (pt) | 2009-03-24 |
| WO2005063257A1 (en) | 2005-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI262181B (en) | Florfenicol prodrug having improved water solubility | |
| US7713950B2 (en) | Antibacterial 1-(4-mono-and di-halomethylsulphonylphenyl)-2-acylamino-3-fluoroproponals and preparation thereof | |
| US5045565A (en) | Novel compounds, pharmaceutical compositions, and methods for treating inflammation and pain | |
| CN104470893A (zh) | 氟化2-氨基-4-(苄基氨基)苯基氨基甲酸酯衍生物 | |
| KR20110013411A (ko) | (ｆ-19)-표지된 ｌ-글루탐산 및 ｌ-글루타민 유도체 (ⅲ), 그의 용도 및 그의 수득 방법 | |
| DE19633480A1 (de) | Oral applizierbare Formulierungen von Chinolon- und Naphthyridoncarbonsäuren | |
| JPS6248678B2 (https=) | ||
| JPWO2021093839A5 (https=) | ||
| US20140187527A1 (en) | Macrocyclic Compounds And Metal Complexes For Bioimaging And Biomedical Applications | |
| JPH03503162A (ja) | 化学療法における毒性特性の改良 | |
| PT88837B (pt) | Processo para a preparacao de acidos e esteres azetidinil-quinolono-carboxilicos | |
| JPH02289568A (ja) | （ｓ）‐７‐（３‐アミノ‐１‐ピロリジニル）‐１‐シクロプロピル‐６‐フルオロ‐１，４‐ジヒドロ‐４‐オキソ‐１，８‐ナフチリジン‐３‐カルボン酸 | |
| WO2019245590A1 (en) | Chemical compounds | |
| CH644613A5 (it) | Mono(2-ammonio-2-idrossimetil-1,3-propandiolo) (2r-cis)-(3-metilossiranil)fosfonato, sua preparazione e composizioni farmaceutiche che lo contengono. | |
| AU2004308913B2 (en) | Florfenicol prodrug having improved water solubility | |
| JP4249928B2 (ja) | 抗腫瘍剤としてのビス−（ｎ，ｎ’−ビス−（２−ハロエチル）アミノ）ホスホルアミデート | |
| WO2019232662A1 (zh) | 一类具有抗癌活性的吲嗪类化合物及其衍生物 | |
| JP2740755B2 (ja) | リシン誘導体、その製造方法及びこれを含有する化粧料組成物 | |
| EP0209000B1 (de) | Embonate von Chinoloncarbonsäuren und ihren Derivaten | |
| JPH09505813A (ja) | ビフェニル沃素化誘導体及びその診断用途 | |
| JPS6243987B2 (https=) | ||
| CA2968483A1 (fr) | Derives hydroxybisphosphoniques hydrosolubles de la doxorubicine | |
| JPS58154589A (ja) | セフアロスポリン誘導体 | |
| JPH0150235B2 (https=) | ||
| JPS61183292A (ja) | 新規化合物、その製法及びそれを含む製薬組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |