FI64377C - Foerfarande foer framstaellning av farmakologiskt vaerdefulla hydroxiaminokolvaetefosfonsyraderivat - Google Patents
Foerfarande foer framstaellning av farmakologiskt vaerdefulla hydroxiaminokolvaetefosfonsyraderivat Download PDFInfo
- Publication number
- FI64377C FI64377C FI772280A FI772280A FI64377C FI 64377 C FI64377 C FI 64377C FI 772280 A FI772280 A FI 772280A FI 772280 A FI772280 A FI 772280A FI 64377 C FI64377 C FI 64377C
- Authority
- FI
- Finland
- Prior art keywords
- acid
- mixture
- reduced pressure
- under reduced
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 90
- 238000002360 preparation method Methods 0.000 title claims description 29
- 230000000144 pharmacologic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 168
- -1 lower alkenoyl Chemical group 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 230000003301 hydrolyzing effect Effects 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 125000001118 alkylidene group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 271
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 186
- 239000000203 mixture Substances 0.000 description 162
- 230000002829 reductive effect Effects 0.000 description 156
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 146
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 100
- 238000003756 stirring Methods 0.000 description 82
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 78
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 66
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 62
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 54
- 238000001816 cooling Methods 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 44
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 238000001914 filtration Methods 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- 239000013078 crystal Substances 0.000 description 38
- 239000007864 aqueous solution Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 29
- 239000007858 starting material Substances 0.000 description 29
- CRZNAZZXMBDMBS-UHFFFAOYSA-N 3-(hydroxyamino)propylphosphonic acid Chemical compound ONCCCP(O)(O)=O CRZNAZZXMBDMBS-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 27
- 235000019253 formic acid Nutrition 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 25
- 239000002244 precipitate Substances 0.000 description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 230000007062 hydrolysis Effects 0.000 description 24
- 238000006460 hydrolysis reaction Methods 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 18
- 239000007788 liquid Substances 0.000 description 16
- 239000000843 powder Substances 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000010908 decantation Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 150000007524 organic acids Chemical class 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 125000002252 acyl group Chemical group 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 150000007529 inorganic bases Chemical class 0.000 description 12
- 150000007530 organic bases Chemical class 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 10
- 239000007795 chemical reaction product Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 230000006181 N-acylation Effects 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 238000005917 acylation reaction Methods 0.000 description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 8
- GJXWDTUCERCKIX-UHFFFAOYSA-N fosmidomycin Chemical compound O=CN(O)CCCP(O)(O)=O GJXWDTUCERCKIX-UHFFFAOYSA-N 0.000 description 8
- 150000007522 mineralic acids Chemical class 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 230000026030 halogenation Effects 0.000 description 7
- 238000005658 halogenation reaction Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- PKMNDDZSIHLLLI-UHFFFAOYSA-N FR900098 Natural products CC(=O)N(O)CCCP(O)(O)=O PKMNDDZSIHLLLI-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 229920001429 chelating resin Polymers 0.000 description 6
- 238000001103 continuous-wave nuclear magnetic resonance spectrum Methods 0.000 description 6
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000002140 halogenating effect Effects 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 6
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- PEIKTSJIUKYDPC-UHFFFAOYSA-N Diethyl 3-Bromopropylphosphonate Chemical compound CCOP(=O)(OCC)CCCBr PEIKTSJIUKYDPC-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 150000008065 acid anhydrides Chemical class 0.000 description 5
- 230000010933 acylation Effects 0.000 description 5
- 239000003513 alkali Substances 0.000 description 5
- 230000000845 anti-microbial effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006664 bond formation reaction Methods 0.000 description 5
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- NSETWVJZUWGCKE-UHFFFAOYSA-N propylphosphonic acid Chemical compound CCCP(O)(O)=O NSETWVJZUWGCKE-UHFFFAOYSA-N 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- ZZPUYRHMTGOTEU-UHFFFAOYSA-M sodium;3-[formyl(hydroxy)amino]propyl-hydroxyphosphinate Chemical compound [Na+].O=CN(O)CCCP(O)([O-])=O ZZPUYRHMTGOTEU-UHFFFAOYSA-M 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 241000588770 Proteus mirabilis Species 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- HSFPUYYGGRYBCD-HNQUOIGGSA-N [(e)-3-(hydroxyamino)prop-1-enyl]phosphonic acid Chemical compound ONC\C=C\P(O)(O)=O HSFPUYYGGRYBCD-HNQUOIGGSA-N 0.000 description 4
- GRGAPWQSBFOAEB-UHFFFAOYSA-N [2-hydroxy-3-(hydroxyamino)propyl]phosphonic acid Chemical compound ONCC(O)CP(O)(O)=O GRGAPWQSBFOAEB-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000003957 anion exchange resin Substances 0.000 description 4
- 244000052616 bacterial pathogen Species 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000002198 insoluble material Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- LCFXFDGYDKNWMD-UHFFFAOYSA-M sodium;3-[acetyl(hydroxy)amino]propyl-hydroxyphosphinate Chemical compound [Na+].CC(=O)N(O)CCCP(O)([O-])=O LCFXFDGYDKNWMD-UHFFFAOYSA-M 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 4
- YTQMZWCJYREOLX-FNORWQNLSA-N (e)-3-bromo-1-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(OCC)\C=C\CBr YTQMZWCJYREOLX-FNORWQNLSA-N 0.000 description 3
- NFDYKBILOZTPSH-UHFFFAOYSA-N 1,2-dibromo-3-diethoxyphosphorylpropane Chemical compound CCOP(=O)(OCC)CC(Br)CBr NFDYKBILOZTPSH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- FUKXIMRHLZJUCG-UHFFFAOYSA-N 2-(diethoxyphosphorylmethyl)oxirane Chemical compound CCOP(=O)(OCC)CC1CO1 FUKXIMRHLZJUCG-UHFFFAOYSA-N 0.000 description 3
- SGLNGTWMRAHPGP-UHFFFAOYSA-N 2-(hydroxyamino)ethylphosphonic acid Chemical compound ONCCP(O)(O)=O SGLNGTWMRAHPGP-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 241000588919 Citrobacter freundii Species 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 241000588697 Enterobacter cloacae Species 0.000 description 3
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 3
- 241000588747 Klebsiella pneumoniae Species 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000588772 Morganella morganii Species 0.000 description 3
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
- 241000588767 Proteus vulgaris Species 0.000 description 3
- 241000588777 Providencia rettgeri Species 0.000 description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 3
- 241000607715 Serratia marcescens Species 0.000 description 3
- 241000607762 Shigella flexneri Species 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- ZPNKMADWQYTQCA-FNORWQNLSA-N [(e)-3-[ethoxycarbonyl(ethoxycarbonyloxy)amino]prop-1-enyl]phosphonic acid Chemical compound CCOC(=O)ON(C(=O)OCC)C\C=C\P(O)(O)=O ZPNKMADWQYTQCA-FNORWQNLSA-N 0.000 description 3
- LYOMUCXUUKSHPX-UHFFFAOYSA-N [3-[formyl(hydroxy)amino]-2-hydroxypropyl]phosphonic acid Chemical compound OP(=O)(O)CC(O)CN(O)C=O LYOMUCXUUKSHPX-UHFFFAOYSA-N 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000012435 aralkylating agent Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- HBMJDPGVDSHYBA-UHFFFAOYSA-N n-(3-diethoxyphosphorylpropyl)hydroxylamine Chemical compound CCOP(=O)(OCC)CCCNO HBMJDPGVDSHYBA-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000006916 nutrient agar Substances 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- PACVILMBTORBQC-KSMVGCCESA-M potassium;[(e)-3-[formyl(hydroxy)amino]prop-1-enyl]-hydroxyphosphinate Chemical compound [K+].O=CN(O)C\C=C\P(O)([O-])=O PACVILMBTORBQC-KSMVGCCESA-M 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 229940007042 proteus vulgaris Drugs 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- HZGAJRVMHROSBR-UHFFFAOYSA-N (2-chloro-2-oxoethyl) benzoate Chemical compound ClC(=O)COC(=O)C1=CC=CC=C1 HZGAJRVMHROSBR-UHFFFAOYSA-N 0.000 description 2
- YTQMZWCJYREOLX-ALCCZGGFSA-N (z)-3-bromo-1-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(OCC)\C=C/CBr YTQMZWCJYREOLX-ALCCZGGFSA-N 0.000 description 2
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 2
- GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 2
- OVABDAYPBKLTNH-UHFFFAOYSA-N 1-bromo-3-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(OCC)CC=CBr OVABDAYPBKLTNH-UHFFFAOYSA-N 0.000 description 2
- SUTSIXJDJYWVRZ-UHFFFAOYSA-N 1-bromo-3-diethoxyphosphorylpropan-2-ol Chemical compound CCOP(=O)(OCC)CC(O)CBr SUTSIXJDJYWVRZ-UHFFFAOYSA-N 0.000 description 2
- ZFQHYXHUKIYLBF-UHFFFAOYSA-N 2-(hydroxyamino)propylphosphonic acid Chemical compound ONC(CP(O)(O)=O)C ZFQHYXHUKIYLBF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JGVWOXDBNKSJCM-CMDGGOBGSA-N 2-methyl-2-[(2-methylpropan-2-yl)oxy-[(e)-prop-1-enyl]phosphoryl]oxypropane Chemical compound C\C=C\P(=O)(OC(C)(C)C)OC(C)(C)C JGVWOXDBNKSJCM-CMDGGOBGSA-N 0.000 description 2
- XILULUXICXANSK-UHFFFAOYSA-N 3-(methoxyamino)propylphosphonic acid Chemical compound CONCCCP(O)(O)=O XILULUXICXANSK-UHFFFAOYSA-N 0.000 description 2
- CXOIECRVHUDBSA-UHFFFAOYSA-N 3-bromopropylphosphonic acid Chemical compound OP(O)(=O)CCCBr CXOIECRVHUDBSA-UHFFFAOYSA-N 0.000 description 2
- TYLVYIHBCLRAHH-UHFFFAOYSA-N 5-(hydroxyamino)pentylphosphonic acid Chemical compound ONCCCCCP(O)(O)=O TYLVYIHBCLRAHH-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 241000588915 Klebsiella aerogenes Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 230000006179 O-acylation Effects 0.000 description 2
- 229920000388 Polyphosphate Polymers 0.000 description 2
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 2
- 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 241000607760 Shigella sonnei Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- QXJUAKPPHRXDCV-UHFFFAOYSA-N [3-(hydroxyamino)-2-methylpropyl]phosphonic acid Chemical compound ONCC(C)CP(O)(O)=O QXJUAKPPHRXDCV-UHFFFAOYSA-N 0.000 description 2
- HTEHHGMQNOQHOU-UHFFFAOYSA-N [3-[ethoxycarbonyl(hydroxy)amino]-2-hydroxypropyl]phosphonic acid Chemical compound CCOC(=O)N(O)CC(O)CP(O)(O)=O HTEHHGMQNOQHOU-UHFFFAOYSA-N 0.000 description 2
- HSJRUKBEAQYHAY-UHFFFAOYSA-N [3-diethoxyphosphorylpropyl(ethoxycarbonyl)amino] ethyl carbonate Chemical compound CCOC(=O)ON(C(=O)OCC)CCCP(=O)(OCC)OCC HSJRUKBEAQYHAY-UHFFFAOYSA-N 0.000 description 2
- HIIYKRJQHUUCLB-UHFFFAOYSA-N [NH4+].C(=O)N(O)CCCP([O-])(O)=O Chemical compound [NH4+].C(=O)N(O)CCCP([O-])(O)=O HIIYKRJQHUUCLB-UHFFFAOYSA-N 0.000 description 2
- HQWSEIPLBPNDQX-UHFFFAOYSA-N [[3-diethoxyphosphoryl-2-(oxan-2-yloxy)propyl]-ethoxycarbonylamino] ethyl carbonate Chemical compound CCOC(=O)ON(C(=O)OCC)CC(CP(=O)(OCC)OCC)OC1CCCCO1 HQWSEIPLBPNDQX-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 150000003855 acyl compounds Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940092559 enterobacter aerogenes Drugs 0.000 description 2
- 150000002169 ethanolamines Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000002196 fr. b Anatomy 0.000 description 2
- 210000003918 fraction a Anatomy 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 230000000055 hyoplipidemic effect Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000003431 oxalo group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000001205 polyphosphate Substances 0.000 description 2
- 235000011176 polyphosphates Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229940115939 shigella sonnei Drugs 0.000 description 2
- GIVARPDUQVHFMQ-UHFFFAOYSA-M sodium;[3-[acetyl(hydroxy)amino]-2-hydroxypropyl]-hydroxyphosphinate Chemical compound [Na+].CC(=O)N(O)CC(O)CP(O)([O-])=O GIVARPDUQVHFMQ-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- QWPMLRJYBBNYCY-UHFFFAOYSA-N (4-methoxyphenyl)methyl 4-bromobenzenesulfonate Chemical compound C1=CC(OC)=CC=C1COS(=O)(=O)C1=CC=C(Br)C=C1 QWPMLRJYBBNYCY-UHFFFAOYSA-N 0.000 description 1
- PZOIHJMCQFTWSK-UHFFFAOYSA-N (6-chlorobenzotriazol-1-yl) benzenesulfonate Chemical compound C12=CC(Cl)=CC=C2N=NN1OS(=O)(=O)C1=CC=CC=C1 PZOIHJMCQFTWSK-UHFFFAOYSA-N 0.000 description 1
- GRZHHTYDZVRPIC-UHFFFAOYSA-N (benzyloxy)acetic acid Chemical compound OC(=O)COCC1=CC=CC=C1 GRZHHTYDZVRPIC-UHFFFAOYSA-N 0.000 description 1
- VBHYLCOEVPIQKH-QPJJXVBHSA-N (e)-1-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(OCC)\C=C\C VBHYLCOEVPIQKH-QPJJXVBHSA-N 0.000 description 1
- GPEHAZBASHNZNU-HWKANZROSA-N (e)-3-bromo-1-dimethoxyphosphorylprop-1-ene Chemical compound COP(=O)(OC)\C=C\CBr GPEHAZBASHNZNU-HWKANZROSA-N 0.000 description 1
- YNRAFGRKFVERMD-UHFFFAOYSA-N (ethoxycarbonylamino) ethyl carbonate Chemical compound CCOC(=O)NOC(=O)OCC YNRAFGRKFVERMD-UHFFFAOYSA-N 0.000 description 1
- GGZXEEFQIXMFBF-CMDGGOBGSA-N (ne)-n-octylidenehydroxylamine Chemical compound CCCCCCC\C=N\O GGZXEEFQIXMFBF-CMDGGOBGSA-N 0.000 description 1
- SRFVZMAZFKFWJI-PLNGDYQASA-N (z)-1-dimethoxyphosphorylprop-1-ene Chemical compound COP(=O)(OC)\C=C/C SRFVZMAZFKFWJI-PLNGDYQASA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- PMTJKESEUJJKOF-UHFFFAOYSA-N 1-[butoxy(3-chloropropyl)phosphoryl]oxybutane Chemical compound CCCCOP(=O)(CCCCl)OCCCC PMTJKESEUJJKOF-UHFFFAOYSA-N 0.000 description 1
- ZHTDTJPDPPKLTG-UHFFFAOYSA-N 1-bromo-3-chlorobutane Chemical compound CC(Cl)CCBr ZHTDTJPDPPKLTG-UHFFFAOYSA-N 0.000 description 1
- GSSVPYDPBHEDBM-UHFFFAOYSA-N 1-bromo-5-diethoxyphosphorylpentane Chemical compound CCOP(=O)(OCC)CCCCCBr GSSVPYDPBHEDBM-UHFFFAOYSA-N 0.000 description 1
- XYKQTKBJOYWFRP-UHFFFAOYSA-N 1-chloro-3-diethoxyphosphoryl-2-methylpropane Chemical compound CCOP(=O)(OCC)CC(C)CCl XYKQTKBJOYWFRP-UHFFFAOYSA-N 0.000 description 1
- XVLSVVVQJFTZNJ-UHFFFAOYSA-N 1-chloro-3-diethoxyphosphorylpropane Chemical compound CCOP(=O)(OCC)CCCCl XVLSVVVQJFTZNJ-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- DMJZWFZICOEEAJ-UHFFFAOYSA-N 2-(4-bromothiophen-3-yl)sulfanylpropanoic acid Chemical compound OC(=O)C(C)SC1=CSC=C1Br DMJZWFZICOEEAJ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- RTVWIHWIBDYISZ-VQHVLOKHSA-N 2-[[(e)-3-bromoprop-1-enyl]-[(2-methylpropan-2-yl)oxy]phosphoryl]oxy-2-methylpropane Chemical compound CC(C)(C)OP(=O)(OC(C)(C)C)\C=C\CBr RTVWIHWIBDYISZ-VQHVLOKHSA-N 0.000 description 1
- MARXMDRWROUXMD-UHFFFAOYSA-N 2-bromoisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Br)C(=O)C2=C1 MARXMDRWROUXMD-UHFFFAOYSA-N 0.000 description 1
- AVZBOAGCVKEESJ-UHFFFAOYSA-O 2-ethyl-1,2-benzoxazol-2-ium-7-ol Chemical class C1=CC(O)=C2O[N+](CC)=CC2=C1 AVZBOAGCVKEESJ-UHFFFAOYSA-O 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- KVTHPKXDLVYNCH-UHFFFAOYSA-N 2-iodoethylbenzene Chemical compound ICCC1=CC=CC=C1 KVTHPKXDLVYNCH-UHFFFAOYSA-N 0.000 description 1
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 1
- TXSJXQCGVVPAET-UHFFFAOYSA-N 2-methylpropyl n-(3-dibutoxyphosphorylpropyl)-n-[(4-methoxyphenyl)methoxy]carbamate Chemical compound CCCCOP(=O)(OCCCC)CCCN(C(=O)OCC(C)C)OCC1=CC=C(OC)C=C1 TXSJXQCGVVPAET-UHFFFAOYSA-N 0.000 description 1
- ITJIAVPHDOKGHM-UHFFFAOYSA-N 2-methylpropyl n-hydroxycarbamate Chemical compound CC(C)COC(=O)NO ITJIAVPHDOKGHM-UHFFFAOYSA-N 0.000 description 1
- BNGOFPJWZUXKNR-UHFFFAOYSA-N 2-oxo-2-phenylacetyl chloride Chemical compound ClC(=O)C(=O)C1=CC=CC=C1 BNGOFPJWZUXKNR-UHFFFAOYSA-N 0.000 description 1
- PUKDBFZXGXGCBD-UHFFFAOYSA-N 2-phenylethyl ethanesulfonate Chemical compound CCS(=O)(=O)OCCC1=CC=CC=C1 PUKDBFZXGXGCBD-UHFFFAOYSA-N 0.000 description 1
- VHORYVBOBIUIDS-UHFFFAOYSA-N 2-propan-2-ylbenzenesulfonyl chloride Chemical compound CC(C)C1=CC=CC=C1S(Cl)(=O)=O VHORYVBOBIUIDS-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- NSHAOELVDPKZIC-UHFFFAOYSA-N 3-(2-ethyl-1,2-oxazol-2-ium-5-yl)benzenesulfonic acid;hydroxide Chemical compound [OH-].O1[N+](CC)=CC=C1C1=CC=CC(S(O)(=O)=O)=C1 NSHAOELVDPKZIC-UHFFFAOYSA-N 0.000 description 1
- NEVHGUXEAHNOJO-UHFFFAOYSA-N 3-[(2-chloroacetyl)-hydroxyamino]propylphosphonic acid Chemical compound ClCC(=O)N(O)CCCP(O)(O)=O NEVHGUXEAHNOJO-UHFFFAOYSA-N 0.000 description 1
- IIWMVQGECOWGCK-UHFFFAOYSA-N 3-[benzoyl(hydroxy)amino]propylphosphonic acid Chemical compound OP(=O)(O)CCCN(O)C(=O)C1=CC=CC=C1 IIWMVQGECOWGCK-UHFFFAOYSA-N 0.000 description 1
- ARZLOMHAHSVNRF-UHFFFAOYSA-N 3-[benzoyloxy(formyl)amino]propylphosphonic acid Chemical compound OP(O)(=O)CCCN(C=O)OC(=O)C1=CC=CC=C1 ARZLOMHAHSVNRF-UHFFFAOYSA-N 0.000 description 1
- CSGUSUJEMIYUBU-UHFFFAOYSA-N 3-[butanoyl(hydroxy)amino]propylphosphonic acid Chemical compound CCCC(=O)N(O)CCCP(O)(O)=O CSGUSUJEMIYUBU-UHFFFAOYSA-N 0.000 description 1
- PNTQTXYBDKTYOI-UHFFFAOYSA-N 3-[formyl(methoxy)amino]propylphosphonic acid Chemical compound CON(C=O)CCCP(O)(O)=O PNTQTXYBDKTYOI-UHFFFAOYSA-N 0.000 description 1
- XSFPIPPKOYPIQE-UHFFFAOYSA-N 3-[hydroxy-(2,2,2-trifluoroacetyl)amino]propylphosphonic acid Chemical compound FC(F)(F)C(=O)N(O)CCCP(O)(O)=O XSFPIPPKOYPIQE-UHFFFAOYSA-N 0.000 description 1
- HQCJUKKNVQZQKQ-UHFFFAOYSA-N 3-[hydroxy-(2-thiophen-2-ylacetyl)amino]propylphosphonic acid Chemical compound OP(=O)(O)CCCN(O)C(=O)CC1=CC=CS1 HQCJUKKNVQZQKQ-UHFFFAOYSA-N 0.000 description 1
- YTQMZWCJYREOLX-UHFFFAOYSA-N 3-bromo-1-diethoxyphosphorylprop-1-ene Chemical class CCOP(=O)(OCC)C=CCBr YTQMZWCJYREOLX-UHFFFAOYSA-N 0.000 description 1
- YPJHXRAHMUKXAE-UHFFFAOYSA-N 3-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(CC=C)OCC YPJHXRAHMUKXAE-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- IGIJSFNBEUBMGB-UHFFFAOYSA-N 4-(cyclohexyliminomethylideneamino)-n,n-diethylcyclohexan-1-amine Chemical compound C1CC(N(CC)CC)CCC1N=C=NC1CCCCC1 IGIJSFNBEUBMGB-UHFFFAOYSA-N 0.000 description 1
- BIVFBEGRHVKMIS-UHFFFAOYSA-N 4-methyl-n-phenylmethoxybenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NOCC1=CC=CC=C1 BIVFBEGRHVKMIS-UHFFFAOYSA-N 0.000 description 1
- TZCYLJGNWDVJRA-UHFFFAOYSA-N 6-chloro-1-hydroxybenzotriazole Chemical compound C1=C(Cl)C=C2N(O)N=NC2=C1 TZCYLJGNWDVJRA-UHFFFAOYSA-N 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
- 239000004475 Arginine Substances 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- JWKDVFBDDDAWNS-UHFFFAOYSA-N C(=O)N(O)CCCP(O)(O)=O.C(O)CN Chemical compound C(=O)N(O)CCCP(O)(O)=O.C(O)CN JWKDVFBDDDAWNS-UHFFFAOYSA-N 0.000 description 1
- RTPHOOMJMRNRMO-UHFFFAOYSA-N CCC(=CC)P(O)(O)=O Chemical compound CCC(=CC)P(O)(O)=O RTPHOOMJMRNRMO-UHFFFAOYSA-N 0.000 description 1
- APYMNUIENWSPNN-UHFFFAOYSA-N CCOC(=O)N(C(C(C)C)P(=O)(O)O)OC(=O)OCC Chemical compound CCOC(=O)N(C(C(C)C)P(=O)(O)O)OC(=O)OCC APYMNUIENWSPNN-UHFFFAOYSA-N 0.000 description 1
- DWMMJUMYCAMJMD-SSDOTTSWSA-N CCOC(N(C[C@H](CP(O)(O)=O)O)OC(OCC)=O)=O Chemical compound CCOC(N(C[C@H](CP(O)(O)=O)O)OC(OCC)=O)=O DWMMJUMYCAMJMD-SSDOTTSWSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- HDFFVHSMHLDSLO-UHFFFAOYSA-N Dibenzyl phosphate Chemical compound C=1C=CC=CC=1COP(=O)(O)OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-N 0.000 description 1
- HDWLUGYOLUHEMN-UHFFFAOYSA-N Dinobuton Chemical compound CCC(C)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1OC(=O)OC(C)C HDWLUGYOLUHEMN-UHFFFAOYSA-N 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical class OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- XNPOFXIBHOVFFH-UHFFFAOYSA-N N-cyclohexyl-N'-(2-(4-morpholinyl)ethyl)carbodiimide Chemical compound C1CCCCC1N=C=NCCN1CCOCC1 XNPOFXIBHOVFFH-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 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
- IJFUIQPMSKYWAC-UHFFFAOYSA-N ONC(CCP(O)(O)=O)O Chemical compound ONC(CCP(O)(O)=O)O IJFUIQPMSKYWAC-UHFFFAOYSA-N 0.000 description 1
- IJFUIQPMSKYWAC-GSVOUGTGSA-N O[C@H](CCP(O)(O)=O)NO Chemical compound O[C@H](CCP(O)(O)=O)NO IJFUIQPMSKYWAC-GSVOUGTGSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 206010034962 Photopsia Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241001660803 Proteus inconstans Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- LYOMUCXUUKSHPX-SCSAIBSYSA-N [(2r)-3-[formyl(hydroxy)amino]-2-hydroxypropyl]phosphonic acid Chemical compound OP(=O)(O)C[C@H](O)CN(O)C=O LYOMUCXUUKSHPX-SCSAIBSYSA-N 0.000 description 1
- OSUAVPPWMFXMIM-UHFFFAOYSA-N [(3-diethoxyphosphoryl-2-hydroxypropyl)-ethoxycarbonylamino] ethyl carbonate Chemical compound CCOC(=O)ON(C(=O)OCC)CC(O)CP(=O)(OCC)OCC OSUAVPPWMFXMIM-UHFFFAOYSA-N 0.000 description 1
- LJCWFOKLHHHANO-DUXPYHPUSA-N [(e)-3-[acetyl(hydroxy)amino]prop-1-enyl]phosphonic acid Chemical compound CC(=O)N(O)C\C=C\P(O)(O)=O LJCWFOKLHHHANO-DUXPYHPUSA-N 0.000 description 1
- YTTBDWKRMPYBDN-HNQUOIGGSA-N [(e)-3-[formyl(hydroxy)amino]prop-1-enyl]phosphonic acid Chemical compound O=CN(O)C\C=C\P(O)(O)=O YTTBDWKRMPYBDN-HNQUOIGGSA-N 0.000 description 1
- DNDJHVJVYGDUDC-UHFFFAOYSA-N [5-diethoxyphosphorylpentyl(ethoxycarbonyl)amino] ethyl carbonate Chemical compound CCOC(=O)ON(C(=O)OCC)CCCCCP(=O)(OCC)OCC DNDJHVJVYGDUDC-UHFFFAOYSA-N 0.000 description 1
- ZKNQUUFQSSPUIX-UHFFFAOYSA-L [Ca+2].C(=O)N(O)CCCP([O-])([O-])=O Chemical compound [Ca+2].C(=O)N(O)CCCP([O-])([O-])=O ZKNQUUFQSSPUIX-UHFFFAOYSA-L 0.000 description 1
- HXZBJFNQKUHAKF-UHFFFAOYSA-N [NH4+].BrCC(CP([O-])(O)=O)O Chemical compound [NH4+].BrCC(CP([O-])(O)=O)O HXZBJFNQKUHAKF-UHFFFAOYSA-N 0.000 description 1
- ULQKQKRUPCDANH-UHFFFAOYSA-M [O-]P(CCN(C=O)O)(O)=O.[K+] Chemical compound [O-]P(CCN(C=O)O)(O)=O.[K+] ULQKQKRUPCDANH-UHFFFAOYSA-M 0.000 description 1
- ZDVDCDLBOLSVGM-UHFFFAOYSA-N [chloro(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(Cl)C1=CC=CC=C1 ZDVDCDLBOLSVGM-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000011126 aluminium potassium sulphate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- OVHDZBAFUMEXCX-UHFFFAOYSA-N benzyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=CC=CC=C1 OVHDZBAFUMEXCX-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- ZDKRMIJRCHPKLW-UHFFFAOYSA-N benzyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CC=C1 ZDKRMIJRCHPKLW-UHFFFAOYSA-N 0.000 description 1
- KQNZLOUWXSAZGD-UHFFFAOYSA-N benzylperoxymethylbenzene Chemical compound C=1C=CC=CC=1COOCC1=CC=CC=C1 KQNZLOUWXSAZGD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000004161 brilliant blue FCF Substances 0.000 description 1
- 235000012745 brilliant blue FCF Nutrition 0.000 description 1
- 229940055580 brilliant blue fcf Drugs 0.000 description 1
- DKSMCEUSSQTGBK-UHFFFAOYSA-N bromous acid Chemical compound OBr=O DKSMCEUSSQTGBK-UHFFFAOYSA-N 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001715 carbamic acids Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- GNVMUORYQLCPJZ-UHFFFAOYSA-N carbamothioic s-acid Chemical compound NC(S)=O GNVMUORYQLCPJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical class CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- QYVGVAWVGWSUOW-UHFFFAOYSA-N dibenzyl sulfate Chemical compound C=1C=CC=CC=1COS(=O)(=O)OCC1=CC=CC=C1 QYVGVAWVGWSUOW-UHFFFAOYSA-N 0.000 description 1
- KDSGPAZGWJOGTA-UHFFFAOYSA-M dibenzyl(dimethyl)azanium;hydroxide Chemical compound [OH-].C=1C=CC=CC=1C[N+](C)(C)CC1=CC=CC=C1 KDSGPAZGWJOGTA-UHFFFAOYSA-M 0.000 description 1
- OSPSWZSRKYCQPF-UHFFFAOYSA-N dibutoxy(oxo)phosphanium Chemical compound CCCCO[P+](=O)OCCCC OSPSWZSRKYCQPF-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- KOQOUPYYZXRULT-UHFFFAOYSA-L disodium N-hydroxy-N-(3-phosphonatopropyl)formamide Chemical compound [Na+].C(=O)N(CCCP([O-])([O-])=O)O.[Na+] KOQOUPYYZXRULT-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- WLJAIEMKTSDOJN-UHFFFAOYSA-N ethyl n-(3-dibutoxyphosphorylpropyl)-n-phenylmethoxycarbamate Chemical compound CCCCOP(=O)(OCCCC)CCCN(C(=O)OCC)OCC1=CC=CC=C1 WLJAIEMKTSDOJN-UHFFFAOYSA-N 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 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
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- YKPFMADHGKNDFC-UHFFFAOYSA-N methyl n-(3-diethoxyphosphorylpropyl)-n-methoxycarbamate Chemical compound CCOP(=O)(OCC)CCCN(OC)C(=O)OC YKPFMADHGKNDFC-UHFFFAOYSA-N 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- NICSJKGTHKHXHJ-UHFFFAOYSA-N n-(2-diethoxyphosphorylethyl)-4-methyl-n-phenylmethoxybenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CCP(=O)(OCC)OCC)OCC1=CC=CC=C1 NICSJKGTHKHXHJ-UHFFFAOYSA-N 0.000 description 1
- FIIAURDOOMZDSO-UHFFFAOYSA-N n-(3-dibutoxyphosphorylpropyl)-n-[(4-methoxyphenyl)methoxy]-4-methylbenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CCCP(=O)(OCCCC)OCCCC)OCC1=CC=C(OC)C=C1 FIIAURDOOMZDSO-UHFFFAOYSA-N 0.000 description 1
- HDBTXCARFLUKHW-UHFFFAOYSA-N n-(3-diethoxyphosphorylpropyl)-4-methyl-n-phenylmethoxybenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CCCP(=O)(OCC)OCC)OCC1=CC=CC=C1 HDBTXCARFLUKHW-UHFFFAOYSA-N 0.000 description 1
- YJZRNHAEJAYEAH-UHFFFAOYSA-N n-(3-diethoxyphosphorylpropyl)-n-hydroxyformamide Chemical compound CCOP(=O)(OCC)CCCN(O)C=O YJZRNHAEJAYEAH-UHFFFAOYSA-N 0.000 description 1
- JVHPKYBRJQNPAT-UHFFFAOYSA-N n-cyclohexyl-2,2-diphenylethenimine Chemical compound C1CCCCC1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 JVHPKYBRJQNPAT-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- MVSMBIBGGPSEHQ-UHFFFAOYSA-N o-[(4-methoxyphenyl)methyl]hydroxylamine Chemical compound COC1=CC=C(CON)C=C1 MVSMBIBGGPSEHQ-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- USHDBZLNUZHGOP-UHFFFAOYSA-N pentyl hypochlorite Chemical compound CCCCCOCl USHDBZLNUZHGOP-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- 229910000065 phosphene Inorganic materials 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- RLEHFYQHNYDXPO-UHFFFAOYSA-M potassium 3-[formyl(hydroxy)amino]propyl-hydroxyphosphinate Chemical compound [K+].C(=O)N(O)CCCP([O-])(O)=O RLEHFYQHNYDXPO-UHFFFAOYSA-M 0.000 description 1
- BDVCDIIOVZUEQA-UHFFFAOYSA-M potassium [3-[formyl(hydroxy)amino]-2-methylpropyl]-hydroxyphosphinate Chemical compound [K+].C(=O)N(O)CC(CP([O-])(O)=O)C BDVCDIIOVZUEQA-UHFFFAOYSA-M 0.000 description 1
- 229940050271 potassium alum Drugs 0.000 description 1
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- XWCIXXXLOAAWPU-UHFFFAOYSA-N prop-1-enylphosphonic acid Chemical compound CC=CP(O)(O)=O XWCIXXXLOAAWPU-UHFFFAOYSA-N 0.000 description 1
- 229940054344 proteus inconstans Drugs 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- VFIZBHJTOHUOEK-UHFFFAOYSA-N s-ethylisothiourea Chemical compound CCSC(N)=N VFIZBHJTOHUOEK-UHFFFAOYSA-N 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- IWNHLFUMKRAZQA-UHFFFAOYSA-M sodium hydroxy(propyl)phosphinate Chemical compound [Na+].CCCP(O)([O-])=O IWNHLFUMKRAZQA-UHFFFAOYSA-M 0.000 description 1
- UHLZJEICLZEUGM-UHFFFAOYSA-M sodium hydroxy-[3-[hydroxy-(2-hydroxyacetyl)amino]propyl]phosphinate Chemical compound [Na+].OCC(=O)N(O)CCCP([O-])(O)=O UHLZJEICLZEUGM-UHFFFAOYSA-M 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- PCAPQADOOHVDEL-UHFFFAOYSA-M sodium;2-[acetyl(hydroxy)amino]ethyl-hydroxyphosphinate Chemical compound [Na+].CC(=O)N(O)CCP(O)([O-])=O PCAPQADOOHVDEL-UHFFFAOYSA-M 0.000 description 1
- CFUCDMRKUNLBRQ-UHFFFAOYSA-M sodium;n,n-diethylethanamine;hydrogen carbonate Chemical compound [Na+].OC([O-])=O.CCN(CC)CC CFUCDMRKUNLBRQ-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940073455 tetraethylammonium hydroxide Drugs 0.000 description 1
- LRGJRHZIDJQFCL-UHFFFAOYSA-M tetraethylazanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)CC LRGJRHZIDJQFCL-UHFFFAOYSA-M 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003560 thiocarbamic acids Chemical class 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- SDRXUONWFFNMIJ-UHFFFAOYSA-N triazatriphosphinine Chemical compound n1npppn1 SDRXUONWFFNMIJ-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 239000001993 wax Substances 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- 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
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3826—Acyclic unsaturated acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cephalosporin Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI821745A FI70594C (fi) | 1976-07-27 | 1982-05-18 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla hydroxiaminkolvaetefosfonsyraderivat |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3133976 | 1976-07-27 | ||
| GB3133976 | 1976-07-27 | ||
| GB4222276 | 1976-10-11 | ||
| GB4222276 | 1976-10-11 | ||
| GB2570077 | 1977-06-20 | ||
| GB31339/76A GB1580899A (en) | 1976-07-27 | 1977-06-20 | Hydroxyaminohydrocarbonphosphonic acid derivatives and production and use thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI772280A FI772280A (es) | 1978-01-28 |
| FI64377B FI64377B (fi) | 1983-07-29 |
| FI64377C true FI64377C (fi) | 1983-11-10 |
Family
ID=27258468
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI772280A FI64377C (fi) | 1976-07-27 | 1977-07-26 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla hydroxiaminokolvaetefosfonsyraderivat |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4182758A (es) |
| JP (1) | JPS5340720A (es) |
| AR (1) | AR226522A1 (es) |
| AT (2) | AT367064B (es) |
| CA (1) | CA1091241A (es) |
| CH (5) | CH640862A5 (es) |
| DE (2) | DE2760320C2 (es) |
| DK (1) | DK149609C (es) |
| ES (3) | ES461084A1 (es) |
| FI (1) | FI64377C (es) |
| FR (1) | FR2474505A1 (es) |
| GB (1) | GB1580899A (es) |
| GR (1) | GR61140B (es) |
| HU (1) | HU182023B (es) |
| IE (1) | IE45536B1 (es) |
| NL (1) | NL7708325A (es) |
| NO (1) | NO157504C (es) |
| OA (1) | OA05725A (es) |
| PH (1) | PH14401A (es) |
| PT (1) | PT66854B (es) |
| SE (1) | SE441360B (es) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4084953A (en) * | 1977-03-09 | 1978-04-18 | Monsanto Company | N-hydroxy-N-phosphonomethylglycines and the herbicidal use thereof |
| US4268503A (en) * | 1978-09-14 | 1981-05-19 | Fujisawa Pharmaceutical Co., Ltd. | Antibacterial composition |
| US4210635A (en) * | 1978-02-15 | 1980-07-01 | Fujisawa Pharmaceutical Co., Ltd. | Antibacterial composition |
| US4693742A (en) * | 1983-12-20 | 1987-09-15 | Rohm And Hass Company | Herbicidal hydroxyamino phosphonic acids and derivatives |
| US5189030A (en) * | 1985-06-11 | 1993-02-23 | Ciba-Geigy Corporation | 1-amino-2-phenylethanephosphonic acids as microbiocides |
| JPH0340299U (es) * | 1989-08-31 | 1991-04-18 | ||
| US6680308B1 (en) | 1998-04-14 | 2004-01-20 | Jomaa Hassan | Use of organophosphorus compounds for the therapeutic and prophylactic treatment of infections |
| DE19825585A1 (de) * | 1998-04-14 | 1999-10-21 | Hassan Jomaa | Verwendung von Aminohydrocarbylphosphonsäurederivaten zur therapeutischen und prophylaktischen Behandlung von Infektionen, die durch Parasiten, Pilze oder Viren hervorgerufen werden |
| DE19843223A1 (de) * | 1998-09-22 | 2000-03-30 | Hassan Jomaa | Phosphororganische Verbindungen und ihre Verwendung |
| AU5034899A (en) * | 1998-07-15 | 2000-02-07 | Jomaa Hassan | Drugs containing phosphoric acid derivatives as active ingredient and their use |
| CN1309659A (zh) * | 1998-07-15 | 2001-08-22 | 哈桑·朱马 | 有机磷化合物及其用途 |
| US6753324B2 (en) | 1998-07-15 | 2004-06-22 | Hassan Jomaa | Phosphorous organic compounds and their use |
| DE19854403A1 (de) * | 1998-11-25 | 2000-05-31 | Hassan Jomaa | Phosphororganische Verbindungen und ihre Verwendung |
| EP1255762A1 (de) * | 2000-02-18 | 2002-11-13 | Jomaa Pharmaka GmbH | Phosphororganische verbindungen und ihre verwendung |
| DE10035189A1 (de) * | 2000-07-20 | 2002-02-21 | Hassan Jomaa | Arzneimittel zur oralen Applikation mit einem Gehalt an 3-N-Formylhydroxylaminopropylphosphonsäureestern oder 3-N-Acetylhydroxylaminopropylphosphonsäureestern als Wirkstoff |
| EP1933848A2 (en) * | 2005-10-06 | 2008-06-25 | Innate Pharma | Phosphoantigen salts of organic bases and methods for their crystallization |
| WO2007088878A1 (ja) | 2006-01-31 | 2007-08-09 | Api Corporation | ベンゾアゼピノン類の製造方法 |
| JP5650642B2 (ja) | 2008-08-01 | 2015-01-07 | バイオキシネス ファーマシューティカルズ， インコーポレイテッド | メチオニンアナログおよびそれらを使用する方法 |
| EP2404601A1 (en) | 2010-07-06 | 2012-01-11 | BioAgency AG | New drug combinations for the treatment of Malaria |
| EP2725029A1 (en) | 2012-10-29 | 2014-04-30 | Laboratoire Biodim | New antibacterial compounds and biological applications thereof |
| US20210261580A1 (en) * | 2018-06-18 | 2021-08-26 | The George Washington University, A Congressionally Chartered Not-For-Profi1 | Antibiotics for veterinary staphylococcal infections |
| WO2021074452A1 (de) | 2019-10-19 | 2021-04-22 | Dmg Deutsche Malaria Gmbh | Kombinationspräparate von 3-n-formylhydroxylaminopropylphosphonsäurederivaten oder 3-n-acetylhydroxylaminopropylphosphonsäurederivaten mit clindamycin und artesunat |
| EP3960176A1 (en) | 2020-08-26 | 2022-03-02 | DMG Deutsche Malaria GmbH | Piperaquine and related drug combinations for use in the treatment of covid-19 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6905272A (es) | 1968-05-15 | 1969-11-18 | ||
| US3764677A (en) * | 1971-06-25 | 1973-10-09 | Gates Rubber Co | Diethyl betaaminoethylphosphonate as an antimicrobial agent |
-
1977
- 1977-06-20 GB GB31339/76A patent/GB1580899A/en not_active Expired
- 1977-07-25 HU HU77FU356A patent/HU182023B/hu not_active IP Right Cessation
- 1977-07-25 PH PH20031A patent/PH14401A/en unknown
- 1977-07-26 GR GR54041A patent/GR61140B/el unknown
- 1977-07-26 FI FI772280A patent/FI64377C/fi not_active IP Right Cessation
- 1977-07-26 DE DE2760320A patent/DE2760320C2/de not_active Expired
- 1977-07-26 SE SE7708592A patent/SE441360B/xx not_active IP Right Cessation
- 1977-07-26 DE DE19772733658 patent/DE2733658A1/de active Granted
- 1977-07-26 CA CA283,566A patent/CA1091241A/en not_active Expired
- 1977-07-26 NO NO772652A patent/NO157504C/no unknown
- 1977-07-26 DK DK337877A patent/DK149609C/da not_active IP Right Cessation
- 1977-07-26 IE IE1555/77A patent/IE45536B1/en unknown
- 1977-07-27 OA OA56240A patent/OA05725A/xx unknown
- 1977-07-27 FR FR7723128A patent/FR2474505A1/fr active Granted
- 1977-07-27 PT PT66854A patent/PT66854B/pt unknown
- 1977-07-27 AR AR268576A patent/AR226522A1/es active
- 1977-07-27 NL NL7708325A patent/NL7708325A/xx not_active Application Discontinuation
- 1977-07-27 ES ES461084A patent/ES461084A1/es not_active Expired
- 1977-07-27 US US05/819,554 patent/US4182758A/en not_active Expired - Lifetime
- 1977-07-27 JP JP9081077A patent/JPS5340720A/ja active Granted
- 1977-07-27 AT AT0550977A patent/AT367064B/de not_active IP Right Cessation
- 1977-07-27 CH CH930777A patent/CH640862A5/de not_active IP Right Cessation
-
1978
- 1978-07-17 ES ES471822A patent/ES471822A1/es not_active Expired
-
1979
- 1979-04-02 ES ES479211A patent/ES479211A1/es not_active Expired
- 1979-08-22 AT AT0564879A patent/AT367430B/de not_active IP Right Cessation
-
1984
- 1984-01-31 CH CH427/84A patent/CH647807A5/de not_active IP Right Cessation
- 1984-01-31 CH CH42584A patent/CH646979A5/de not_active IP Right Cessation
- 1984-01-31 CH CH42684A patent/CH646980A5/de not_active IP Right Cessation
- 1984-01-31 CH CH42484A patent/CH646978A5/de not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI64377C (fi) | Foerfarande foer framstaellning av farmakologiskt vaerdefulla hydroxiaminokolvaetefosfonsyraderivat | |
| US4206156A (en) | Hydroxyaminohydrocarbonphosphonic acids | |
| RU2266909C2 (ru) | Водорастворимые азольные соединения и способ их получения | |
| KR960010418B1 (ko) | 디포스폰산 유도체 및 이들을 함유하는 제약 조성물 | |
| US8404664B2 (en) | Phosphonated Rifamycins and uses thereof for the prevention and treatment of bone and joint infections | |
| LU83117A1 (fr) | Antibiotiques a noyau beta-lactame,et procede pour les preparer | |
| JP2009114202A (ja) | ホスフォノセフェム誘導体、その製造法および用途 | |
| IE58614B1 (en) | Derivatives of methylene-bisphosphonic acid, process f their preparation and a pharmaceutical composition | |
| JPH0351716B2 (es) | ||
| EP0099553A2 (en) | Cephem compounds, process and intermediates for their preparation and pharmaceutical compositions containing them | |
| CA2133444A1 (en) | Novel acylated phospholipid drugs | |
| JP4579496B2 (ja) | 水溶性アゾール化合物の改良された方法 | |
| SE453400B (sv) | Forfarande for framstellning av fosfonsyraderivat genom odling av en stam horande till streptomyces rubellomurinus, streptomyces rubellomurinus subsp. indigoferus eller streptomyces lavendulae | |
| KR20000057283A (ko) | 세팔로스포린 유도체 | |
| US4325951A (en) | 1-Oxadethiacephalosporin derivatives and antibacterial use thereof | |
| US3849482A (en) | Amine salts of cis-propenylphosphonic acid | |
| US5006515A (en) | Pharmaceuticals, phosphorus-containing 2-isoxazolines and isoxazoles contained therein | |
| SE445350B (sv) | Oximderivat av 3-azidometyl-7-amino-tiazolyl-acetamido-cefalosporansyra och dess anvendning som antibiotika | |
| KR820000104B1 (ko) | 신규 하이드록시아미노 하이드로 카르본포스폰산 유도체의 제조방법 | |
| KR820001611B1 (ko) | 신규 하이드록시아미노 하이드로 카르본 포스폰산 유도체의 제조방법 | |
| KR820001610B1 (ko) | 신규 하이드록시아미노 하이드로카르본포스폰산 유도체의 제조방법 | |
| HUT73769A (en) | New cephalosporins containing a substituted benzyloxyimino radical in position 7, their preparation process, their use as medicaments | |
| US4365066A (en) | 2(4-n-Hexadecyl amino or oxy phenyl) 5 ethoxy oxazoleacetic acid derivatives | |
| KR810000288B1 (ko) | 몬산 및 이소몬산 유도체의 제조방법 | |
| HU176880B (en) | Process for pproducing new ceph-3-eme-4-carboxylic acid derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: FUJISAWA PHARMACEUTICAL CO. LTD. |