SE460849B - Hypoglykemiska 5-substituerade oxazolidin-2,4-dioner - Google Patents
Hypoglykemiska 5-substituerade oxazolidin-2,4-dionerInfo
- Publication number
- SE460849B SE460849B SE8104542A SE8104542A SE460849B SE 460849 B SE460849 B SE 460849B SE 8104542 A SE8104542 A SE 8104542A SE 8104542 A SE8104542 A SE 8104542A SE 460849 B SE460849 B SE 460849B
- Authority
- SE
- Sweden
- Prior art keywords
- chloro
- dione
- oxazolidine
- mol
- ethyl
- Prior art date
Links
- -1 5-SUBSTITUTED OXAZOLIDINE-2,4-DIONE Chemical class 0.000 title claims description 129
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 60
- 239000000460 chlorine Substances 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- VIFHRIZELSXPGV-UHFFFAOYSA-N CC(=O)NCl(N)OCC1=CC=CC=C1 Chemical compound CC(=O)NCl(N)OCC1=CC=CC=C1 VIFHRIZELSXPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- DDCYYCUMAFYDDU-UHFFFAOYSA-N methyl thiohypochlorite Chemical compound CSCl DDCYYCUMAFYDDU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 204
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 156
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 239000000243 solution Substances 0.000 description 99
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 91
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 77
- 239000011541 reaction mixture Substances 0.000 description 73
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 66
- 239000000203 mixture Substances 0.000 description 63
- 239000003921 oil Substances 0.000 description 59
- 235000019198 oils Nutrition 0.000 description 59
- 238000000034 method Methods 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
- 239000000499 gel Substances 0.000 description 53
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
- 238000004458 analytical method Methods 0.000 description 50
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 46
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 45
- 229910052757 nitrogen Inorganic materials 0.000 description 44
- 238000002360 preparation method Methods 0.000 description 42
- 239000007787 solid Substances 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 description 38
- 229910052799 carbon Inorganic materials 0.000 description 37
- 239000000047 product Substances 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- 239000012267 brine Substances 0.000 description 33
- 238000001953 recrystallisation Methods 0.000 description 31
- 230000035484 reaction time Effects 0.000 description 30
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 30
- 239000000284 extract Substances 0.000 description 24
- 238000002844 melting Methods 0.000 description 24
- 230000008018 melting Effects 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- 239000002253 acid Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 230000002218 hypoglycaemic effect Effects 0.000 description 20
- 150000001477 2,4-oxazolidinediones Chemical class 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 17
- 239000012043 crude product Substances 0.000 description 17
- 238000001704 evaporation Methods 0.000 description 17
- 230000008020 evaporation Effects 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 12
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 239000002243 precursor Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 150000002463 imidates Chemical class 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 239000012452 mother liquor Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 238000009833 condensation Methods 0.000 description 7
- 230000005494 condensation Effects 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- QMDIZIDCORWBJK-UHFFFAOYSA-N 1,3-dichloro-2-(1,3-dichloropropan-2-yloxy)propane Chemical compound ClCC(CCl)OC(CCl)CCl QMDIZIDCORWBJK-UHFFFAOYSA-N 0.000 description 6
- SBYYYVAMWBVIIX-UHFFFAOYSA-N 5-phenyl-1,3-oxazolidine-2,4-dione Chemical compound O1C(=O)NC(=O)C1C1=CC=CC=C1 SBYYYVAMWBVIIX-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 235000013877 carbamide Nutrition 0.000 description 6
- 239000002024 ethyl acetate extract Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 238000007446 glucose tolerance test Methods 0.000 description 6
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- YUJYVSIJMJJPLB-UHFFFAOYSA-N 2-(2-chloro-6-methoxyphenyl)-2-hydroxyacetamide Chemical compound COC1=CC=CC(Cl)=C1C(O)C(N)=O YUJYVSIJMJJPLB-UHFFFAOYSA-N 0.000 description 5
- XKHXOKLIRSKVHN-UHFFFAOYSA-N 2-[2-(trifluoromethyl)phenyl]-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1C(F)(F)F XKHXOKLIRSKVHN-UHFFFAOYSA-N 0.000 description 5
- UHXUZNJCLHADGD-UHFFFAOYSA-N 2-chloro-6-methoxybenzaldehyde Chemical compound COC1=CC=CC(Cl)=C1C=O UHXUZNJCLHADGD-UHFFFAOYSA-N 0.000 description 5
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 150000003335 secondary amines Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 5
- 238000001665 trituration Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- YFQUMJGYGHQFBV-UHFFFAOYSA-N 2-fluoronaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(F)=CC=C21 YFQUMJGYGHQFBV-UHFFFAOYSA-N 0.000 description 4
- PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 4
- CUMROJNWXHIHIV-UHFFFAOYSA-N 5-(2-chloro-6-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=CC(Cl)=C1C1C(=O)NC(=O)O1 CUMROJNWXHIHIV-UHFFFAOYSA-N 0.000 description 4
- ULAQKPXNVOJZJW-UHFFFAOYSA-N 5-(2-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=CC=C1C1C(=O)NC(=O)O1 ULAQKPXNVOJZJW-UHFFFAOYSA-N 0.000 description 4
- UXSMKNBVXKFWCJ-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C(Cl)C=C1C1C(=O)NC(=O)O1 UXSMKNBVXKFWCJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000000378 dietary effect Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000004615 ingredient Substances 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 3
- SZKBFOWEOKWEDD-UHFFFAOYSA-N 2,6-dimethoxynaphthalene-1-carbaldehyde Chemical compound O=CC1=C(OC)C=CC2=CC(OC)=CC=C21 SZKBFOWEOKWEDD-UHFFFAOYSA-N 0.000 description 3
- DQZNEARAAKUGKL-UHFFFAOYSA-N 2-(2,5-dimethylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CC1=CC=C(C)C(C(O[Si](C)(C)C)C#N)=C1 DQZNEARAAKUGKL-UHFFFAOYSA-N 0.000 description 3
- IFIQCQZSRSSKNS-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)-2-hydroxyacetamide Chemical compound NC(=O)C(O)C1=C(Cl)C=CC=C1Cl IFIQCQZSRSSKNS-UHFFFAOYSA-N 0.000 description 3
- MXKBSPSTPDCQOL-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=C(F)C=CC=C1F MXKBSPSTPDCQOL-UHFFFAOYSA-N 0.000 description 3
- JOKJBHYSHIMMAO-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=C(F)C=CC=C1Cl JOKJBHYSHIMMAO-UHFFFAOYSA-N 0.000 description 3
- QMDFSFBQZSVNGM-UHFFFAOYSA-N 2-(2-ethoxynaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC=CC2=C(C(O[Si](C)(C)C)C#N)C(OCC)=CC=C21 QMDFSFBQZSVNGM-UHFFFAOYSA-N 0.000 description 3
- MAYFTTLXNLPOKU-UHFFFAOYSA-N 2-(2-ethoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CCOC1=CC=CC=C1C(O[Si](C)(C)C)C#N MAYFTTLXNLPOKU-UHFFFAOYSA-N 0.000 description 3
- RXXQFIVKYXGKSA-UHFFFAOYSA-N 2-(2-fluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1F RXXQFIVKYXGKSA-UHFFFAOYSA-N 0.000 description 3
- VJOFWPFIKPTAKW-UHFFFAOYSA-N 2-(2-nitrophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1[N+]([O-])=O VJOFWPFIKPTAKW-UHFFFAOYSA-N 0.000 description 3
- NBVVTILJGGPFDU-UHFFFAOYSA-N 2-(3-fluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC(F)=C1 NBVVTILJGGPFDU-UHFFFAOYSA-N 0.000 description 3
- RMDXARJBHYOEIS-UHFFFAOYSA-N 2-(3-phenoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 RMDXARJBHYOEIS-UHFFFAOYSA-N 0.000 description 3
- GQRHDMBGHIVTRA-UHFFFAOYSA-N 2-(5-chloro-2-methoxyphenyl)-2-hydroxyacetamide Chemical compound COC1=CC=C(Cl)C=C1C(O)C(N)=O GQRHDMBGHIVTRA-UHFFFAOYSA-N 0.000 description 3
- IPDDLKUEUDNUEM-UHFFFAOYSA-N 2-(5-fluoro-2-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=C(F)C=C1C(O[Si](C)(C)C)C#N IPDDLKUEUDNUEM-UHFFFAOYSA-N 0.000 description 3
- XUYBVCMQWBSFJR-UHFFFAOYSA-N 2-(5-fluoro-2-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CC1=CC=C(F)C=C1C(O[Si](C)(C)C)C#N XUYBVCMQWBSFJR-UHFFFAOYSA-N 0.000 description 3
- IMNKQTWVJHODOS-UHFFFAOYSA-N 2-ethoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(OCC)=CC=C21 IMNKQTWVJHODOS-UHFFFAOYSA-N 0.000 description 3
- WIAZTPUQHUFMQA-UHFFFAOYSA-N 2-methylnaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(C)=CC=C21 WIAZTPUQHUFMQA-UHFFFAOYSA-N 0.000 description 3
- DTAFQWDNWAXRLX-UHFFFAOYSA-N 2-phenyl-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1 DTAFQWDNWAXRLX-UHFFFAOYSA-N 0.000 description 3
- XPTFTIWHVUFKJU-UHFFFAOYSA-N 5-(2,6-difluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound FC1=CC=CC(F)=C1C1C(=O)NC(=O)O1 XPTFTIWHVUFKJU-UHFFFAOYSA-N 0.000 description 3
- KRSACFUPPCULSN-UHFFFAOYSA-N 5-(2-chloro-6-methoxyphenyl)-1,3-oxazolidine-2,4-dione;sodium Chemical compound [Na].COC1=CC=CC(Cl)=C1C1C(=O)NC(=O)O1 KRSACFUPPCULSN-UHFFFAOYSA-N 0.000 description 3
- SOUYSLIRYPWRBZ-UHFFFAOYSA-N 5-(2-fluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound FC1=CC=CC=C1C1C(=O)NC(=O)O1 SOUYSLIRYPWRBZ-UHFFFAOYSA-N 0.000 description 3
- LKXXYQWSDWFHTD-UHFFFAOYSA-N 5-(2-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound CC1=CC=CC=C1C1C(=O)NC(=O)O1 LKXXYQWSDWFHTD-UHFFFAOYSA-N 0.000 description 3
- JVUJRLHWDLJULI-UHFFFAOYSA-N 5-chloro-2-ethoxybenzaldehyde Chemical compound CCOC1=CC=C(Cl)C=C1C=O JVUJRLHWDLJULI-UHFFFAOYSA-N 0.000 description 3
- XANGJMDFCYLTED-UHFFFAOYSA-N 5-naphthalen-1-yl-2-sulfanylidene-1,3-oxazolidin-4-one Chemical compound O=C1NC(=S)OC1C1=CC=CC2=CC=CC=C12 XANGJMDFCYLTED-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 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 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- FVLTWAWRNOVORT-UHFFFAOYSA-N [2-amino-1-(2-chloro-6-methoxyphenyl)-2-oxoethyl] formate Chemical compound COC1=CC=CC(Cl)=C1C(OC=O)C(N)=O FVLTWAWRNOVORT-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- BVEWMNTVZPFPQI-UHFFFAOYSA-N dialuric acid Chemical compound OC1C(=O)NC(=O)NC1=O BVEWMNTVZPFPQI-UHFFFAOYSA-N 0.000 description 3
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- PUMHNAKSYDQLOJ-UHFFFAOYSA-N ethyl 2-(2-chloro-6-methoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=C(Cl)C=CC=C1OC PUMHNAKSYDQLOJ-UHFFFAOYSA-N 0.000 description 3
- NHDVHAFTIAGUOL-UHFFFAOYSA-N ethyl 2-(2-fluorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC=C1F NHDVHAFTIAGUOL-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- JCGNDDUYTRNOFT-UHFFFAOYSA-N oxolane-2,4-dione Chemical compound O=C1COC(=O)C1 JCGNDDUYTRNOFT-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- WZWGGYFEOBVNLA-UHFFFAOYSA-N sodium;dihydrate Chemical compound O.O.[Na] WZWGGYFEOBVNLA-UHFFFAOYSA-N 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- CHLICZRVGGXEOD-UHFFFAOYSA-N 1-Methoxy-4-methylbenzene Chemical compound COC1=CC=C(C)C=C1 CHLICZRVGGXEOD-UHFFFAOYSA-N 0.000 description 2
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
- IXLSVQMYQRAMEW-UHFFFAOYSA-N 1-chloro-4-ethoxybenzene Chemical compound CCOC1=CC=C(Cl)C=C1 IXLSVQMYQRAMEW-UHFFFAOYSA-N 0.000 description 2
- SDGMUBWPXBSKCT-UHFFFAOYSA-N 1-chloro-4-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Cl)C(C)=C1 SDGMUBWPXBSKCT-UHFFFAOYSA-N 0.000 description 2
- DMIYKWPEFRFTPY-UHFFFAOYSA-N 2,6-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(Cl)=C1C=O DMIYKWPEFRFTPY-UHFFFAOYSA-N 0.000 description 2
- SOWRUJSGHKNOKN-UHFFFAOYSA-N 2,6-difluorobenzaldehyde Chemical compound FC1=CC=CC(F)=C1C=O SOWRUJSGHKNOKN-UHFFFAOYSA-N 0.000 description 2
- SRYYLXDOTXDYQW-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-2-hydroxyacetamide Chemical compound NC(=O)C(O)C1=C(F)C=CC=C1Cl SRYYLXDOTXDYQW-UHFFFAOYSA-N 0.000 description 2
- BXESWGJBKBSLCP-UHFFFAOYSA-N 2-(2-ethoxy-6-fluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CCOC1=CC=CC(F)=C1C(O[Si](C)(C)C)C#N BXESWGJBKBSLCP-UHFFFAOYSA-N 0.000 description 2
- CFRDMJUUJGVMRT-UHFFFAOYSA-N 2-(2-fluoronaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC=C2C(C(C#N)O[Si](C)(C)C)=C(F)C=CC2=C1 CFRDMJUUJGVMRT-UHFFFAOYSA-N 0.000 description 2
- DJFBDNWHWUGNNT-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=C(C)C=C1C(O[Si](C)(C)C)C#N DJFBDNWHWUGNNT-UHFFFAOYSA-N 0.000 description 2
- WFYYOKSYJTXXGR-UHFFFAOYSA-N 2-(2-methoxy-6-nitrophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=CC([N+]([O-])=O)=C1C(O[Si](C)(C)C)C#N WFYYOKSYJTXXGR-UHFFFAOYSA-N 0.000 description 2
- ZWIHLRRBWNXPKX-UHFFFAOYSA-N 2-(2-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CC1=CC=CC=C1C(O[Si](C)(C)C)C#N ZWIHLRRBWNXPKX-UHFFFAOYSA-N 0.000 description 2
- LBAOKJLBNMLKLN-UHFFFAOYSA-N 2-(2-phenylmethoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1OCC1=CC=CC=C1 LBAOKJLBNMLKLN-UHFFFAOYSA-N 0.000 description 2
- SYXSJROJYFVLLN-UHFFFAOYSA-N 2-(3-fluoro-2-methoxy-5-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=C(F)C=C(C)C=C1C(O[Si](C)(C)C)C#N SYXSJROJYFVLLN-UHFFFAOYSA-N 0.000 description 2
- QXVSCYSIXYYSHO-UHFFFAOYSA-N 2-(5-chloro-2-methoxy-3-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=C(C)C=C(Cl)C=C1C(O[Si](C)(C)C)C#N QXVSCYSIXYYSHO-UHFFFAOYSA-N 0.000 description 2
- RTCYLPXXBGAFGL-UHFFFAOYSA-N 2-(5-chloro-2-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=C(Cl)C=C1C(O[Si](C)(C)C)C#N RTCYLPXXBGAFGL-UHFFFAOYSA-N 0.000 description 2
- OCLGHQGOTMUJQP-UHFFFAOYSA-N 2-(7-fluoronaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=C(F)C=C2C(C(C#N)O[Si](C)(C)C)=CC=CC2=C1 OCLGHQGOTMUJQP-UHFFFAOYSA-N 0.000 description 2
- OACPOWYLLGHGCR-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound FC1=CC=CC(Cl)=C1C=O OACPOWYLLGHGCR-UHFFFAOYSA-N 0.000 description 2
- IVKPBNVMLKJSFG-UHFFFAOYSA-N 2-chloronaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(Cl)=CC=C21 IVKPBNVMLKJSFG-UHFFFAOYSA-N 0.000 description 2
- IKVQETBZMVZUIL-UHFFFAOYSA-N 2-ethoxy-5-fluorobenzaldehyde Chemical compound CCOC1=CC=C(F)C=C1C=O IKVQETBZMVZUIL-UHFFFAOYSA-N 0.000 description 2
- VHZCPJWEAMDEKL-UHFFFAOYSA-N 2-ethoxy-6-fluorobenzaldehyde Chemical compound CCOC1=CC=CC(F)=C1C=O VHZCPJWEAMDEKL-UHFFFAOYSA-N 0.000 description 2
- DUVJMSPTZMCSTQ-UHFFFAOYSA-N 2-ethoxybenzaldehyde Chemical compound CCOC1=CC=CC=C1C=O DUVJMSPTZMCSTQ-UHFFFAOYSA-N 0.000 description 2
- FZIBGCDUHZBOLA-UHFFFAOYSA-N 2-fluoro-6-hydroxybenzaldehyde Chemical compound OC1=CC=CC(F)=C1C=O FZIBGCDUHZBOLA-UHFFFAOYSA-N 0.000 description 2
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- MFKMYYPWCWXHBY-UHFFFAOYSA-N 2-hydroxyacetamide;hydrochloride Chemical compound Cl.NC(=O)CO MFKMYYPWCWXHBY-UHFFFAOYSA-N 0.000 description 2
- YWVSKFXYEWMHEO-UHFFFAOYSA-N 2-methoxy-5-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C=C1C=O YWVSKFXYEWMHEO-UHFFFAOYSA-N 0.000 description 2
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- VHXIEGGPMOEWNK-UHFFFAOYSA-N 3-chloro-5-fluoro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(F)C=C1C=O VHXIEGGPMOEWNK-UHFFFAOYSA-N 0.000 description 2
- LUCYVSMQRYCVHN-UHFFFAOYSA-N 3-chloro-5-fluoro-2-methoxybenzaldehyde Chemical compound COC1=C(Cl)C=C(F)C=C1C=O LUCYVSMQRYCVHN-UHFFFAOYSA-N 0.000 description 2
- FMDHZKRBTPCCBK-UHFFFAOYSA-N 3-chloro-6-methoxy-2-methylbenzaldehyde Chemical compound COC1=CC=C(Cl)C(C)=C1C=O FMDHZKRBTPCCBK-UHFFFAOYSA-N 0.000 description 2
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- UJBTWDXPWHSHCC-UHFFFAOYSA-N 5-(2,5-dimethylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound CC1=CC=C(C)C(C2C(NC(=O)O2)=O)=C1 UJBTWDXPWHSHCC-UHFFFAOYSA-N 0.000 description 2
- MGXCYBJZYSTREA-UHFFFAOYSA-N 5-(2-chloro-6-fluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound FC1=CC=CC(Cl)=C1C1C(=O)NC(=O)O1 MGXCYBJZYSTREA-UHFFFAOYSA-N 0.000 description 2
- WMYCHCQVNMDKRL-UHFFFAOYSA-N 5-(2-ethoxy-5-fluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound CCOC1=CC=C(F)C=C1C1C(=O)NC(=O)O1 WMYCHCQVNMDKRL-UHFFFAOYSA-N 0.000 description 2
- UFKAYRNOYLAMAV-UHFFFAOYSA-N 5-(2-fluoro-6-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=CC(F)=C1C1C(=O)NC(=O)O1 UFKAYRNOYLAMAV-UHFFFAOYSA-N 0.000 description 2
- OMLRUFVOBJOSJV-UHFFFAOYSA-N 5-(2-methoxynaphthalen-1-yl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C2C=CC=CC2=C1C1OC(=O)NC1=O OMLRUFVOBJOSJV-UHFFFAOYSA-N 0.000 description 2
- MPAJVZQLPIFKKT-UHFFFAOYSA-N 5-(2-methylnaphthalen-1-yl)-1,3-oxazolidine-2,4-dione Chemical compound CC1=CC=C2C=CC=CC2=C1C1OC(=O)NC1=O MPAJVZQLPIFKKT-UHFFFAOYSA-N 0.000 description 2
- HPKGRYJVZDVIGV-UHFFFAOYSA-N 5-(2-phenylmethoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound O1C(=O)NC(=O)C1C1=CC=CC=C1OCC1=CC=CC=C1 HPKGRYJVZDVIGV-UHFFFAOYSA-N 0.000 description 2
- SBEDNFAPSOUIAZ-UHFFFAOYSA-N 5-(3-chloro-6-methoxy-2-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C(Cl)C(C)=C1C1C(=O)NC(=O)O1 SBEDNFAPSOUIAZ-UHFFFAOYSA-N 0.000 description 2
- PXYQVBQLMHTRMN-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound ClC1=CC=CC(C2C(NC(=O)O2)=O)=C1 PXYQVBQLMHTRMN-UHFFFAOYSA-N 0.000 description 2
- YUNUZICDVVRCRV-UHFFFAOYSA-N 5-(3-fluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound FC1=CC=CC(C2C(NC(=O)O2)=O)=C1 YUNUZICDVVRCRV-UHFFFAOYSA-N 0.000 description 2
- HCNPZCQGYCMOQF-UHFFFAOYSA-N 5-(3-phenoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound O1C(=O)NC(=O)C1C1=CC=CC(OC=2C=CC=CC=2)=C1 HCNPZCQGYCMOQF-UHFFFAOYSA-N 0.000 description 2
- AUIHFDZXLSJZED-UHFFFAOYSA-N 5-(4-fluorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1C(=O)NC(=O)O1 AUIHFDZXLSJZED-UHFFFAOYSA-N 0.000 description 2
- JNQYVRGRPXSDIM-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-1,3-oxazolidine-2,4-dione;sodium Chemical compound [Na].COC1=CC=C(Cl)C=C1C1C(=O)NC(=O)O1 JNQYVRGRPXSDIM-UHFFFAOYSA-N 0.000 description 2
- DILBEGIIJTTYOI-UHFFFAOYSA-N 5-[2-(trifluoromethyl)phenyl]-1,3-oxazolidine-2,4-dione Chemical compound FC(F)(F)C1=CC=CC=C1C1C(=O)NC(=O)O1 DILBEGIIJTTYOI-UHFFFAOYSA-N 0.000 description 2
- FJLSWFYFARDZHG-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-1,3-oxazolidine-2,4-dione Chemical compound FC(F)(F)C1=CC=CC(C2C(NC(=O)O2)=O)=C1 FJLSWFYFARDZHG-UHFFFAOYSA-N 0.000 description 2
- IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
- MBOXPKNOGZJXPK-UHFFFAOYSA-N 5-fluoro-2-methylbenzaldehyde Chemical compound CC1=CC=C(F)C=C1C=O MBOXPKNOGZJXPK-UHFFFAOYSA-N 0.000 description 2
- ZKSLQFFTSJWDBI-UHFFFAOYSA-N 5-phenyl-2-sulfanylidene-1,3-oxazolidin-4-one Chemical compound O=C1NC(=S)OC1C1=CC=CC=C1 ZKSLQFFTSJWDBI-UHFFFAOYSA-N 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
- HQBCFROPFWQZIP-UHFFFAOYSA-N 7-chloronaphthalene-1-carbaldehyde Chemical compound C1=CC=C(C=O)C2=CC(Cl)=CC=C21 HQBCFROPFWQZIP-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229920002261 Corn starch Polymers 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000005915 ammonolysis reaction Methods 0.000 description 2
- 229960004977 anhydrous lactose Drugs 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 229940043237 diethanolamine Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- QNBRSYZPBAUFGZ-UHFFFAOYSA-N ethyl 2-(2,5-dimethylphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(C)=CC=C1C QNBRSYZPBAUFGZ-UHFFFAOYSA-N 0.000 description 2
- INWXBMCYHDMCCD-UHFFFAOYSA-N ethyl 2-(2-ethoxy-6-fluorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=C(F)C=CC=C1OCC INWXBMCYHDMCCD-UHFFFAOYSA-N 0.000 description 2
- NOKZIZCAAOWOTG-UHFFFAOYSA-N ethyl 2-(2-ethoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC=C1OCC NOKZIZCAAOWOTG-UHFFFAOYSA-N 0.000 description 2
- XDVGLRWKVFAWQP-UHFFFAOYSA-N ethyl 2-(2-fluoronaphthalen-1-yl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.C1=CC=C2C(C(O)C(=N)OCC)=C(F)C=CC2=C1 XDVGLRWKVFAWQP-UHFFFAOYSA-N 0.000 description 2
- UBYDVXAMJBSHDG-UHFFFAOYSA-N ethyl 2-(3-fluorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC(F)=C1 UBYDVXAMJBSHDG-UHFFFAOYSA-N 0.000 description 2
- LNYQUUIYYCWMFF-UHFFFAOYSA-N ethyl 2-(5-chloro-2-methoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(Cl)=CC=C1OC LNYQUUIYYCWMFF-UHFFFAOYSA-N 0.000 description 2
- LKSPYEJRACLGQG-UHFFFAOYSA-N ethyl 2-(5-fluoro-2-methoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(F)=CC=C1OC LKSPYEJRACLGQG-UHFFFAOYSA-N 0.000 description 2
- LZRDVWCMTHTQOT-UHFFFAOYSA-N ethyl 2-(5-fluoro-2-methylphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(F)=CC=C1C LZRDVWCMTHTQOT-UHFFFAOYSA-N 0.000 description 2
- RYMQUEWEGGNTCA-UHFFFAOYSA-N ethyl 2-(7-fluoronaphthalen-1-yl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(C(O)C(=N)OCC)=CC=CC2=C1 RYMQUEWEGGNTCA-UHFFFAOYSA-N 0.000 description 2
- BVHQVCKQIXYNIP-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methoxyphenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC=C1OC BVHQVCKQIXYNIP-UHFFFAOYSA-N 0.000 description 2
- WNESYLZCYMVXRF-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methylphenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC=C1C WNESYLZCYMVXRF-UHFFFAOYSA-N 0.000 description 2
- YQLXFXVENSSXMS-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-phenylmethoxynaphthalen-1-yl)ethanimidate;hydrochloride Chemical compound Cl.C1=CC2=CC=CC=C2C(C(O)C(=N)OCC)=C1OCC1=CC=CC=C1 YQLXFXVENSSXMS-UHFFFAOYSA-N 0.000 description 2
- MRHUEGYFGLBNFN-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-phenylmethoxyphenyl)ethanimidate Chemical compound CCOC(=N)C(O)C1=CC=CC=C1OCC1=CC=CC=C1 MRHUEGYFGLBNFN-UHFFFAOYSA-N 0.000 description 2
- HDKRWWAFWGYBOT-UHFFFAOYSA-N ethyl 2-hydroxy-2-[2-(trifluoromethyl)phenyl]ethanimidate Chemical compound CCOC(=N)C(O)C1=CC=CC=C1C(F)(F)F HDKRWWAFWGYBOT-UHFFFAOYSA-N 0.000 description 2
- LBXKFXRERIKGHN-UHFFFAOYSA-N ethyl 2-hydroxy-2-phenylethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC=C1 LBXKFXRERIKGHN-UHFFFAOYSA-N 0.000 description 2
- 229940012017 ethylenediamine Drugs 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 229940116357 potassium thiocyanate Drugs 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 238000007790 scraping Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
- BIIBYWQGRFWQKM-JVVROLKMSA-N (2S)-N-[4-(cyclopropylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]-2-[[(E)-3-(2,4-dichlorophenyl)prop-2-enoyl]amino]-4,4-dimethylpentanamide Chemical compound CC(C)(C)C[C@@H](C(NC(C[C@H](CCN1)C1=O)C(C(NC1CC1)=O)=O)=O)NC(/C=C/C(C=CC(Cl)=C1)=C1Cl)=O BIIBYWQGRFWQKM-JVVROLKMSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- FQXOOGHQVPKHPG-UHFFFAOYSA-N 1,3-diazinane-2,4,5-trione Chemical compound O=C1NCC(=O)C(=O)N1 FQXOOGHQVPKHPG-UHFFFAOYSA-N 0.000 description 1
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 1
- GZTMCZAOQTVOJK-UHFFFAOYSA-N 1,3-dioxolan-4-one Chemical compound O=C1COCO1 GZTMCZAOQTVOJK-UHFFFAOYSA-N 0.000 description 1
- YKVAYVVLBBAJRL-UHFFFAOYSA-N 1-(2-phenylmethoxyphenyl)propan-1-ol Chemical compound CCC(O)C1=CC=CC=C1OCC1=CC=CC=C1 YKVAYVVLBBAJRL-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- XTXLAKQKGNTWSR-UHFFFAOYSA-N 1-[2-(trifluoromethyl)phenyl]propan-1-ol Chemical class CCC(O)C1=CC=CC=C1C(F)(F)F XTXLAKQKGNTWSR-UHFFFAOYSA-N 0.000 description 1
- SZSJCUKIEPGUMF-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]propan-1-ol Chemical compound CCC(O)C1=CC=CC(C(F)(F)F)=C1 SZSJCUKIEPGUMF-UHFFFAOYSA-N 0.000 description 1
- IPWBFGUBXWMIPR-UHFFFAOYSA-N 1-bromo-2-fluorobenzene Chemical compound FC1=CC=CC=C1Br IPWBFGUBXWMIPR-UHFFFAOYSA-N 0.000 description 1
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 1
- PURLWQWDGIIYBG-UHFFFAOYSA-N 1-ethoxy-4-fluorobenzene Chemical compound CCOC1=CC=C(F)C=C1 PURLWQWDGIIYBG-UHFFFAOYSA-N 0.000 description 1
- WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 description 1
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
- AHKDVDYNDXGFPP-UHFFFAOYSA-N 2,6-dimethoxynaphthalene Chemical compound C1=C(OC)C=CC2=CC(OC)=CC=C21 AHKDVDYNDXGFPP-UHFFFAOYSA-N 0.000 description 1
- NWIDNBBMRITEIW-UHFFFAOYSA-N 2-(2,6-dimethoxynaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=C(OC)C=CC2=CC(OC)=CC=C21 NWIDNBBMRITEIW-UHFFFAOYSA-N 0.000 description 1
- LOYKSNILPZSMLV-UHFFFAOYSA-N 2-(2-chloro-6-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=CC(Cl)=C1C(O[Si](C)(C)C)C#N LOYKSNILPZSMLV-UHFFFAOYSA-N 0.000 description 1
- XNQQMQFYWMTLJN-UHFFFAOYSA-N 2-(2-chloronaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC=C2C(C(C#N)O[Si](C)(C)C)=C(Cl)C=CC2=C1 XNQQMQFYWMTLJN-UHFFFAOYSA-N 0.000 description 1
- JBQUIFCGWMPSPW-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC=C1Cl JBQUIFCGWMPSPW-UHFFFAOYSA-N 0.000 description 1
- OLLNXLLMRZZOCR-UHFFFAOYSA-N 2-(2-ethoxy-5-fluorophenyl)-2-trimethylsilylacetonitrile Chemical compound CCOC1=CC=C(F)C=C1C(C#N)[Si](C)(C)C OLLNXLLMRZZOCR-UHFFFAOYSA-N 0.000 description 1
- QLPDNMXWNVZPHF-UHFFFAOYSA-N 2-(2-methoxynaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC=CC2=C(C(O[Si](C)(C)C)C#N)C(OC)=CC=C21 QLPDNMXWNVZPHF-UHFFFAOYSA-N 0.000 description 1
- WUBUKZXSHDELIA-UHFFFAOYSA-N 2-(2-methoxyphenyl)-2-trimethylsilylacetonitrile Chemical compound COC1=CC=CC=C1C(C#N)[Si](C)(C)C WUBUKZXSHDELIA-UHFFFAOYSA-N 0.000 description 1
- BCXQPILRBQANLT-UHFFFAOYSA-N 2-(2-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=CC=C1C(O[Si](C)(C)C)C#N BCXQPILRBQANLT-UHFFFAOYSA-N 0.000 description 1
- KYCVZQALMJGRSJ-UHFFFAOYSA-N 2-(2-methylnaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC=CC2=C(C(O[Si](C)(C)C)C#N)C(C)=CC=C21 KYCVZQALMJGRSJ-UHFFFAOYSA-N 0.000 description 1
- XIXBHVUFYQRODZ-UHFFFAOYSA-N 2-(2-phenylmethoxynaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=CC2=CC=CC=C2C(C(C#N)O[Si](C)(C)C)=C1OCC1=CC=CC=C1 XIXBHVUFYQRODZ-UHFFFAOYSA-N 0.000 description 1
- DYWLCMCUMMBVAA-UHFFFAOYSA-N 2-(3-chloro-5-fluoro-2-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=C(Cl)C=C(F)C=C1C(O[Si](C)(C)C)C#N DYWLCMCUMMBVAA-UHFFFAOYSA-N 0.000 description 1
- YRZFCIFDXWUQNP-UHFFFAOYSA-N 2-(3-chloro-6-methoxy-2-methylphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=C(Cl)C(C)=C1C(O[Si](C)(C)C)C#N YRZFCIFDXWUQNP-UHFFFAOYSA-N 0.000 description 1
- RNOOTRCEYZUFOL-UHFFFAOYSA-N 2-(3-chlorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=CC(Cl)=C1 RNOOTRCEYZUFOL-UHFFFAOYSA-N 0.000 description 1
- CPPJDRQDEDCYBA-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OC(C#N)C1=CC=C(F)C=C1 CPPJDRQDEDCYBA-UHFFFAOYSA-N 0.000 description 1
- MHXRIYWJXJHTMI-UHFFFAOYSA-N 2-(5-bromo-2-methoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound COC1=CC=C(Br)C=C1C(O[Si](C)(C)C)C#N MHXRIYWJXJHTMI-UHFFFAOYSA-N 0.000 description 1
- WRCSWEGAAYHJGL-UHFFFAOYSA-N 2-(5-chloro-2-ethoxyphenyl)-2-trimethylsilyloxyacetonitrile Chemical compound CCOC1=CC=C(Cl)C=C1C(O[Si](C)(C)C)C#N WRCSWEGAAYHJGL-UHFFFAOYSA-N 0.000 description 1
- VYUGUZAOTXPNTG-UHFFFAOYSA-N 2-(7-chloronaphthalen-1-yl)-2-trimethylsilyloxyacetonitrile Chemical compound C1=C(Cl)C=C2C(C(C#N)O[Si](C)(C)C)=CC=CC2=C1 VYUGUZAOTXPNTG-UHFFFAOYSA-N 0.000 description 1
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-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
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
- KVUPQEKUVSNRCD-UHFFFAOYSA-N 2-amino-1,3-oxazol-4-one Chemical compound NC1=NC(=O)CO1 KVUPQEKUVSNRCD-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- YJEMGEBDXDPBSP-UHFFFAOYSA-N 2-bromo-4-chloro-1-methoxybenzene Chemical compound COC1=CC=C(Cl)C=C1Br YJEMGEBDXDPBSP-UHFFFAOYSA-N 0.000 description 1
- JIQXVIJARQLCOY-UHFFFAOYSA-N 2-bromo-4-fluoro-1-methoxybenzene Chemical compound COC1=CC=C(F)C=C1Br JIQXVIJARQLCOY-UHFFFAOYSA-N 0.000 description 1
- KBYZNPRCCAXLPI-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound ClC1=C(C=O)C(=CC=C1)F.ClC1=C(C=O)C(=CC=C1)F KBYZNPRCCAXLPI-UHFFFAOYSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- IHYVIZUUNOUNAW-UHFFFAOYSA-N 2-chlorobenzaldehyde 2-(2-chlorophenyl)-2-trimethylsilyloxyacetonitrile Chemical compound ClC1=C(C=O)C=CC=C1.ClC1=C(C=CC=C1)C(C#N)O[Si](C)(C)C IHYVIZUUNOUNAW-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- FOVXANGOLMXKES-UHFFFAOYSA-N 2-fluoro-1-methoxy-4-methylbenzene Chemical compound COC1=CC=C(C)C=C1F FOVXANGOLMXKES-UHFFFAOYSA-N 0.000 description 1
- BAGQBTMEEISJLK-UHFFFAOYSA-N 2-fluoronaphthalene Chemical compound C1=CC=CC2=CC(F)=CC=C21 BAGQBTMEEISJLK-UHFFFAOYSA-N 0.000 description 1
- CJVIGQCGJUDKOE-UHFFFAOYSA-N 2-methoxy-5-methylbenzaldehyde Chemical compound COC1=CC=C(C)C=C1C=O CJVIGQCGJUDKOE-UHFFFAOYSA-N 0.000 description 1
- NQCOCZQZPQKVGI-UHFFFAOYSA-N 2-methoxy-6-nitrobenzaldehyde Chemical compound COC1=CC=CC([N+]([O-])=O)=C1C=O NQCOCZQZPQKVGI-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 1
- VEMDBXGFPCYWJJ-UHFFFAOYSA-N 2-phenylmethoxy-1-naphthalenecarboxaldehyde Chemical compound C1=CC2=CC=CC=C2C(C=O)=C1OCC1=CC=CC=C1 VEMDBXGFPCYWJJ-UHFFFAOYSA-N 0.000 description 1
- PBEJTRAJWCNHRS-UHFFFAOYSA-N 2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OCC1=CC=CC=C1 PBEJTRAJWCNHRS-UHFFFAOYSA-N 0.000 description 1
- GCSVNNODDIEGEX-UHFFFAOYSA-N 2-sulfanylidene-1,3-oxazolidin-4-one Chemical compound O=C1COC(=S)N1 GCSVNNODDIEGEX-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- SVVZXVWJFYDKNR-UHFFFAOYSA-N 2-trimethylsilyloxyacetonitrile Chemical compound C[Si](C)(C)OCC#N SVVZXVWJFYDKNR-UHFFFAOYSA-N 0.000 description 1
- GGJYTWBLIQYOCS-UHFFFAOYSA-N 3-(2-methoxy-5-nitrophenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C([N+]([O-])=O)C=C1N1C(=O)OCC1=O GGJYTWBLIQYOCS-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- AAOHGIBACYAWHC-UHFFFAOYSA-N 3-acetyl-5-(5-chloro-2-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C(Cl)C=C1C1C(=O)N(C(C)=O)C(=O)O1 AAOHGIBACYAWHC-UHFFFAOYSA-N 0.000 description 1
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
- JKPTVXAFTUKDQS-UHFFFAOYSA-N 3-fluoro-2-methoxy-5-methylbenzaldehyde Chemical compound COC1=C(F)C=C(C)C=C1C=O JKPTVXAFTUKDQS-UHFFFAOYSA-N 0.000 description 1
- MRLGCTNJRREZHZ-UHFFFAOYSA-N 3-phenoxybenzaldehyde Chemical compound O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 MRLGCTNJRREZHZ-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940077398 4-methyl anisole Drugs 0.000 description 1
- JYJFNDQBESEHJQ-UHFFFAOYSA-N 5,5-dimethyloxazolidine-2,4-dione Chemical compound CC1(C)OC(=O)NC1=O JYJFNDQBESEHJQ-UHFFFAOYSA-N 0.000 description 1
- SBHKZHACUNPBFA-UHFFFAOYSA-N 5-(1h-pyrrol-2-yl)-1,3-oxazolidine-2,4-dione Chemical compound O1C(=O)NC(=O)C1C1=CC=CN1 SBHKZHACUNPBFA-UHFFFAOYSA-N 0.000 description 1
- OKRLULSUSJGUSR-UHFFFAOYSA-N 5-(2-aminophenyl)-1,3-oxazolidine-2,4-dione 5-(2-nitrophenyl)-1,3-oxazolidine-2,4-dione hydrochloride Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)C1C(NC(O1)=O)=O.Cl.NC1=C(C=CC=C1)C1C(NC(O1)=O)=O OKRLULSUSJGUSR-UHFFFAOYSA-N 0.000 description 1
- SYIMDELDEUOWOM-UHFFFAOYSA-N 5-(2-aminophenyl)-1,3-oxazolidine-2,4-dione;hydrochloride Chemical compound Cl.NC1=CC=CC=C1C1C(=O)NC(=O)O1 SYIMDELDEUOWOM-UHFFFAOYSA-N 0.000 description 1
- MEPKTUKJOXNFKO-UHFFFAOYSA-N 5-(2-chloro-6-fluorophenyl)-1,3-oxazolidine Chemical compound FC1=CC=CC(Cl)=C1C1OCNC1 MEPKTUKJOXNFKO-UHFFFAOYSA-N 0.000 description 1
- VKWXBLCIKDWVFA-UHFFFAOYSA-N 5-(2-chloro-6-fluorophenyl)-1,3-oxazolidine-2,4-dione ethyl 2-(2-chloro-6-fluorophenyl)-2-hydroxyethanimidate hydrochloride Chemical compound Cl.ClC1=C(C(=CC=C1)F)C(C(OCC)=N)O.ClC1=C(C(=CC=C1)F)C1C(NC(O1)=O)=O VKWXBLCIKDWVFA-UHFFFAOYSA-N 0.000 description 1
- JNXGKOHDMSKDLW-UHFFFAOYSA-N 5-(2-chloro-6-methoxyphenyl)-1,3-oxazolidine-2,4-dione;sodium;dihydrate Chemical compound O.O.[Na].COC1=CC=CC(Cl)=C1C1C(=O)NC(=O)O1 JNXGKOHDMSKDLW-UHFFFAOYSA-N 0.000 description 1
- HCEABIDLJMUSEJ-UHFFFAOYSA-N 5-(2-chloro-6-methoxyphenyl)-n-methyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound O=C1N(C(=O)NC)C(=O)OC1C1=C(Cl)C=CC=C1OC HCEABIDLJMUSEJ-UHFFFAOYSA-N 0.000 description 1
- HJNLVMQPUWWPAZ-UHFFFAOYSA-N 5-(2-chlorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound ClC1=CC=CC=C1C1C(=O)NC(=O)O1 HJNLVMQPUWWPAZ-UHFFFAOYSA-N 0.000 description 1
- GTJKMXHJMJXFBA-UHFFFAOYSA-N 5-(2-ethoxynaphthalen-1-yl)-1,3-oxazolidine-2,4-dione Chemical compound CCOC1=CC=C2C=CC=CC2=C1C1OC(=O)NC1=O GTJKMXHJMJXFBA-UHFFFAOYSA-N 0.000 description 1
- UZCIXEQCAPMPKV-UHFFFAOYSA-N 5-(2-ethoxyphenyl)-5-hydroxy-1,3-diazinane-2,4,6-trione Chemical compound CCOC1=CC=CC=C1C1(O)C(=O)NC(=O)NC1=O UZCIXEQCAPMPKV-UHFFFAOYSA-N 0.000 description 1
- FOWRGKPOZCNQTB-UHFFFAOYSA-N 5-(2-fluoronaphthalen-1-yl)-1,3-oxazolidine-2,4-dione Chemical compound FC1=CC=C2C=CC=CC2=C1C1OC(=O)NC1=O FOWRGKPOZCNQTB-UHFFFAOYSA-N 0.000 description 1
- XDJKQMRTOMCOJX-UHFFFAOYSA-N 5-(2-methoxy-5-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C(C)C=C1C1C(=O)NC(=O)O1 XDJKQMRTOMCOJX-UHFFFAOYSA-N 0.000 description 1
- QVFFNUJRJMPSJG-UHFFFAOYSA-N 5-(2-methoxy-6-nitrophenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=CC([N+]([O-])=O)=C1C1C(=O)NC(=O)O1 QVFFNUJRJMPSJG-UHFFFAOYSA-N 0.000 description 1
- RYAITGRQOYVWHN-UHFFFAOYSA-N 5-(2-nitrophenyl)-1,3-oxazolidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC=C1C1C(=O)NC(=O)O1 RYAITGRQOYVWHN-UHFFFAOYSA-N 0.000 description 1
- VXXFPWKVAQFPQI-UHFFFAOYSA-N 5-(2-phenylmethoxynaphthalen-1-yl)-1,3-oxazolidine-2,4-dione Chemical compound O1C(=O)NC(=O)C1C(C1=CC=CC=C1C=C1)=C1OCC1=CC=CC=C1 VXXFPWKVAQFPQI-UHFFFAOYSA-N 0.000 description 1
- LRVLAHKIQWPWCY-UHFFFAOYSA-N 5-(4-aminophenyl)-1,3-oxazolidine-2,4-dione Chemical compound C1=CC(N)=CC=C1C1C(=O)NC(=O)O1 LRVLAHKIQWPWCY-UHFFFAOYSA-N 0.000 description 1
- VPVNXXAWDQOVMV-UHFFFAOYSA-N 5-(4-chlorophenyl)-1,3-oxazolidine-2,4-dione Chemical compound C1=CC(Cl)=CC=C1C1C(=O)NC(=O)O1 VPVNXXAWDQOVMV-UHFFFAOYSA-N 0.000 description 1
- FAHOYQVKOPIHKB-UHFFFAOYSA-N 5-(4-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C1C(=O)NC(=O)O1 FAHOYQVKOPIHKB-UHFFFAOYSA-N 0.000 description 1
- YDBXXANXIVZRNL-UHFFFAOYSA-N 5-(4-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1C1C(=O)NC(=O)O1 YDBXXANXIVZRNL-UHFFFAOYSA-N 0.000 description 1
- CMHQSRTVAWYAHQ-UHFFFAOYSA-N 5-(5-bromo-2-methoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=CC=C(Br)C=C1C1C(=O)NC(=O)O1 CMHQSRTVAWYAHQ-UHFFFAOYSA-N 0.000 description 1
- YORLWDGQTRSTLN-UHFFFAOYSA-N 5-(5-chloro-2-ethoxyphenyl)-1,3-oxazolidine-2,4-dione Chemical compound CCOC1=CC=C(Cl)C=C1C1C(=O)NC(=O)O1 YORLWDGQTRSTLN-UHFFFAOYSA-N 0.000 description 1
- YHYNKQHMTKHXIM-UHFFFAOYSA-N 5-(5-chloro-2-methoxy-3-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound COC1=C(C)C=C(Cl)C=C1C1C(=O)NC(=O)O1 YHYNKQHMTKHXIM-UHFFFAOYSA-N 0.000 description 1
- FKRTXSOGNIBEAO-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-4-ethoxy-3h-1,3-oxazol-2-one Chemical compound N1C(=O)OC(C=2C(=CC=C(Cl)C=2)OC)=C1OCC FKRTXSOGNIBEAO-UHFFFAOYSA-N 0.000 description 1
- YPHOBTMBFCOKGK-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-n,n-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound COC1=CC=C(Cl)C=C1C1C(=O)N(C(=O)N(C)C)C(=O)O1 YPHOBTMBFCOKGK-UHFFFAOYSA-N 0.000 description 1
- GSVPSCFQWLZQJS-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-n-cyclohexyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound COC1=CC=C(Cl)C=C1C1C(=O)N(C(=O)NC2CCCCC2)C(=O)O1 GSVPSCFQWLZQJS-UHFFFAOYSA-N 0.000 description 1
- BTDDCGCZXDUJHF-UHFFFAOYSA-N 5-(5-fluoro-2-methylphenyl)-1,3-oxazolidine-2,4-dione Chemical compound CC1=CC=C(F)C=C1C1C(=O)NC(=O)O1 BTDDCGCZXDUJHF-UHFFFAOYSA-N 0.000 description 1
- HXTWDGGMXZXOIV-UHFFFAOYSA-N 5-chloro-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Cl)C=C1C=O HXTWDGGMXZXOIV-UHFFFAOYSA-N 0.000 description 1
- CRLDWFVRQNUUSZ-UHFFFAOYSA-N 5-fluoro-2-methoxybenzaldehyde Chemical compound COC1=CC=C(F)C=C1C=O CRLDWFVRQNUUSZ-UHFFFAOYSA-N 0.000 description 1
- KVCGYEULFRLZTJ-UHFFFAOYSA-N 7-fluoronaphthalene-1-carbaldehyde Chemical compound C1=CC=C(C=O)C2=CC(F)=CC=C21 KVCGYEULFRLZTJ-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 244000232745 Bactris gasipaes Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- GEGZDECILNPUNN-UHFFFAOYSA-N COC1=C(C=O)C=CC=C1.COC1=C(C=CC=C1)C(C#N)O[Si](C)(C)C Chemical compound COC1=C(C=O)C=CC=C1.COC1=C(C=CC=C1)C(C#N)O[Si](C)(C)C GEGZDECILNPUNN-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VOROMYGEEDCJTL-UHFFFAOYSA-N Cl.NC1=C(C=CC=C1)C1C(NC(O1)=O)=O.C(C)(=O)NC1=C(C=CC=C1)C1C(NC(O1)=O)=O Chemical compound Cl.NC1=C(C=CC=C1)C1C(NC(O1)=O)=O.C(C)(=O)NC1=C(C=CC=C1)C1C(NC(O1)=O)=O VOROMYGEEDCJTL-UHFFFAOYSA-N 0.000 description 1
- RSDLANVLDCGUHR-UHFFFAOYSA-N ClC1=C(C(=CC=C1)F)C1C(NC(O1)=O)=O.ClC1=C(C(=CC=C1)OC)C1C(NC(O1)=O)=O Chemical compound ClC1=C(C(=CC=C1)F)C1C(NC(O1)=O)=O.ClC1=C(C(=CC=C1)OC)C1C(NC(O1)=O)=O RSDLANVLDCGUHR-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- JKTWQRSZVINHPK-UHFFFAOYSA-N FC1=CC=C(C=O)C=C1.FC1=CC=C(C=C1)C(C#N)O[Si](C)(C)C Chemical compound FC1=CC=C(C=O)C=C1.FC1=CC=C(C=C1)C(C#N)O[Si](C)(C)C JKTWQRSZVINHPK-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- RLAHWVDQYNDAGG-UHFFFAOYSA-N Methanetriol Chemical class OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 238000006828 Rosenmund reduction reaction Methods 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- LTQFJXJITNOBOS-UHFFFAOYSA-N [K].ClC=1C=CC(=C(C1)C1C(NC(O1)=O)=O)OC Chemical compound [K].ClC=1C=CC(=C(C1)C1C(NC(O1)=O)=O)OC LTQFJXJITNOBOS-UHFFFAOYSA-N 0.000 description 1
- FGEJMPPDXKJWAM-UHFFFAOYSA-L [O-]OOOOOO[O-].[Na+].[Na+] Chemical compound [O-]OOOOOO[O-].[Na+].[Na+] FGEJMPPDXKJWAM-UHFFFAOYSA-L 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000005224 alkoxybenzenes Chemical class 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- LMIZORQOLSLQRY-UHFFFAOYSA-N benzene;naphthalene Chemical class C1=CC=CC=C1.C1=CC=CC2=CC=CC=C21 LMIZORQOLSLQRY-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 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
- 238000004364 calculation method Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- MVGLBXWFOSHCCP-UHFFFAOYSA-N chloroform;tetrachloromethane Chemical compound ClC(Cl)Cl.ClC(Cl)(Cl)Cl MVGLBXWFOSHCCP-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000006324 decarbonylation Effects 0.000 description 1
- 238000006606 decarbonylation reaction Methods 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- CRKCUSYNINXXSM-UHFFFAOYSA-N ethyl 2-(2,5-dimethylphenyl)-2,2-dihydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)(O)C1=CC(C)=CC=C1C CRKCUSYNINXXSM-UHFFFAOYSA-N 0.000 description 1
- IYMVQFODLPTOEL-UHFFFAOYSA-N ethyl 2-(2,6-dimethoxynaphthalen-1-yl)-2-hydroxyethanimidate Chemical compound COC1=CC=C2C(C(O)C(=N)OCC)=C(OC)C=CC2=C1 IYMVQFODLPTOEL-UHFFFAOYSA-N 0.000 description 1
- MGKCUCSLQOWNDC-UHFFFAOYSA-N ethyl 2-(2-chloro-6-fluorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=C(F)C=CC=C1Cl MGKCUCSLQOWNDC-UHFFFAOYSA-N 0.000 description 1
- GDWNGPDDKSRPLH-UHFFFAOYSA-N ethyl 2-(2-chloronaphthalen-1-yl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.C1=CC=C2C(C(O)C(=N)OCC)=C(Cl)C=CC2=C1 GDWNGPDDKSRPLH-UHFFFAOYSA-N 0.000 description 1
- JRSQCJLZDSFZKP-UHFFFAOYSA-N ethyl 2-(2-ethoxynaphthalen-1-yl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.C1=CC=C2C(C(O)C(=N)OCC)=C(OCC)C=CC2=C1 JRSQCJLZDSFZKP-UHFFFAOYSA-N 0.000 description 1
- QNWULQVUGUUZFR-UHFFFAOYSA-N ethyl 2-(3-chloro-5-fluoro-2-methoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(F)=CC(Cl)=C1OC QNWULQVUGUUZFR-UHFFFAOYSA-N 0.000 description 1
- IPCFXLKDECOUKT-UHFFFAOYSA-N ethyl 2-(3-chlorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=CC(Cl)=C1 IPCFXLKDECOUKT-UHFFFAOYSA-N 0.000 description 1
- SXFLPYAIXPDBBE-UHFFFAOYSA-N ethyl 2-(3-fluoro-2-methoxy-5-methylphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(C)=CC(F)=C1OC SXFLPYAIXPDBBE-UHFFFAOYSA-N 0.000 description 1
- WTHPXDYOEVYATG-UHFFFAOYSA-N ethyl 2-(4-fluorophenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC=C(F)C=C1 WTHPXDYOEVYATG-UHFFFAOYSA-N 0.000 description 1
- RTANUBTUJWBRFL-UHFFFAOYSA-N ethyl 2-(5-bromo-2-methoxyphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(Br)=CC=C1OC RTANUBTUJWBRFL-UHFFFAOYSA-N 0.000 description 1
- COOABHLYAKWUIT-UHFFFAOYSA-N ethyl 2-(5-chloro-2-ethoxyphenyl)-2-hydroxyethanimidate Chemical compound CCOC(=N)C(O)C1=CC(Cl)=CC=C1OCC COOABHLYAKWUIT-UHFFFAOYSA-N 0.000 description 1
- ANISUQAAWSMCRS-UHFFFAOYSA-N ethyl 2-(5-chloro-2-methoxy-3-methylphenyl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(Cl)=CC(C)=C1OC ANISUQAAWSMCRS-UHFFFAOYSA-N 0.000 description 1
- YHECVHYFKOQRAS-UHFFFAOYSA-N ethyl 2-(5-chloro-2-methoxyphenyl)-2-hydroxyethanimidate Chemical compound CCOC(=N)C(O)C1=CC(Cl)=CC=C1OC YHECVHYFKOQRAS-UHFFFAOYSA-N 0.000 description 1
- KCVARQMYYXDNEC-UHFFFAOYSA-N ethyl 2-(5-fluoro-2-methoxyphenyl)-2-hydroxyethanimidate Chemical compound CCOC(=N)C(O)C1=CC(F)=CC=C1OC KCVARQMYYXDNEC-UHFFFAOYSA-N 0.000 description 1
- KHRMSIDWOCZVNC-UHFFFAOYSA-N ethyl 2-(7-chloronaphthalen-1-yl)-2-hydroxyethanimidate;hydrochloride Chemical compound Cl.C1=C(Cl)C=C2C(C(O)C(=N)OCC)=CC=CC2=C1 KHRMSIDWOCZVNC-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- KEDLKOLOVVQMOW-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methoxy-5-methylphenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC(C)=CC=C1OC KEDLKOLOVVQMOW-UHFFFAOYSA-N 0.000 description 1
- QIEYLRWWAMCENU-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methoxy-5-nitrophenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=CC([N+]([O-])=O)=CC=C1OC QIEYLRWWAMCENU-UHFFFAOYSA-N 0.000 description 1
- UZNGKFLUKQYKIJ-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methoxy-6-nitrophenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)C(O)C1=C(OC)C=CC=C1[N+]([O-])=O UZNGKFLUKQYKIJ-UHFFFAOYSA-N 0.000 description 1
- POAHPTHIUNRTMW-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methoxynaphthalen-1-yl)ethanimidate Chemical compound C1=CC=C2C(C(O)C(=N)OCC)=C(OC)C=CC2=C1 POAHPTHIUNRTMW-UHFFFAOYSA-N 0.000 description 1
- ZASGAAWGTBEHOH-UHFFFAOYSA-N ethyl 2-hydroxy-2-(2-methylnaphthalen-1-yl)ethanimidate;hydrochloride Chemical compound Cl.C1=CC=C2C(C(O)C(=N)OCC)=C(C)C=CC2=C1 ZASGAAWGTBEHOH-UHFFFAOYSA-N 0.000 description 1
- QIGHEAHYUFSCHZ-UHFFFAOYSA-N ethyl 2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethanimidate Chemical compound CCOC(=N)C(O)C1=CC=CC(C(F)(F)F)=C1 QIGHEAHYUFSCHZ-UHFFFAOYSA-N 0.000 description 1
- WYRRCHSAVYXEJB-UHFFFAOYSA-N ethyl 2-hydroxyethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CO WYRRCHSAVYXEJB-UHFFFAOYSA-N 0.000 description 1
- LKHYFCSSVZVVNF-UHFFFAOYSA-N ethyl hexanoate;sodium Chemical compound [Na].CCCCCC(=O)OCC LKHYFCSSVZVVNF-UHFFFAOYSA-N 0.000 description 1
- DRDBNKYFCOLNQO-UHFFFAOYSA-N ethyl n-phenylmethanimidate Chemical compound CCOC=NC1=CC=CC=C1 DRDBNKYFCOLNQO-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-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
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- XRVHSOXXNQTWAW-UHFFFAOYSA-N n-(methylcarbamoyl)acetamide Chemical compound CNC(=O)NC(C)=O XRVHSOXXNQTWAW-UHFFFAOYSA-N 0.000 description 1
- SSSMPTRUVQBIIO-UHFFFAOYSA-N n-[2-(2,4-dioxo-1,3-oxazolidin-3-yl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1N1C(=O)OCC1=O SSSMPTRUVQBIIO-UHFFFAOYSA-N 0.000 description 1
- NQRAFAJRALBNII-UHFFFAOYSA-N n-[2-(2,4-dioxo-1,3-oxazolidin-5-yl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1C1C(=O)NC(=O)O1 NQRAFAJRALBNII-UHFFFAOYSA-N 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 238000010653 organometallic reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 229960005152 pentetrazol Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000011110 re-filtration Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- KWEPZBBBGYRION-UHFFFAOYSA-M sodium 2,6-dichlorobenzaldehyde hydrogen sulfite Chemical compound S([O-])(O)=O.[Na+].ClC1=C(C=O)C(=CC=C1)Cl KWEPZBBBGYRION-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 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
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 238000007514 turning Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/44—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by —CHO groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/008—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with tri- or tetrahalomethyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/513—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an etherified hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/546—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/55—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/44—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/46—Sulfur atoms
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17320680A | 1980-07-28 | 1980-07-28 | |
US06/222,202 US4367234A (en) | 1980-07-28 | 1981-01-02 | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
Publications (2)
Publication Number | Publication Date |
---|---|
SE8104542L SE8104542L (sv) | 1982-01-29 |
SE460849B true SE460849B (sv) | 1989-11-27 |
Family
ID=26868872
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SE8104542A SE460849B (sv) | 1980-07-28 | 1981-07-24 | Hypoglykemiska 5-substituerade oxazolidin-2,4-dioner |
Country Status (27)
Country | Link |
---|---|
US (1) | US4367234A (no) |
KR (3) | KR850000381B1 (no) |
AR (3) | AR228061A1 (no) |
AT (1) | AT376424B (no) |
AU (1) | AU526905B2 (no) |
CA (1) | CA1155855A (no) |
CH (1) | CH653025A5 (no) |
DD (1) | DD202149A5 (no) |
DE (1) | DE3129309A1 (no) |
DK (1) | DK151882C (no) |
ES (3) | ES8306367A1 (no) |
FI (1) | FI77457C (no) |
FR (1) | FR2487348B1 (no) |
GB (3) | GB2083810B (no) |
GR (1) | GR74590B (no) |
HU (1) | HU185682B (no) |
IE (1) | IE51427B1 (no) |
IL (1) | IL63422A (no) |
IT (1) | IT1138110B (no) |
LU (1) | LU83512A1 (no) |
NL (1) | NL8103536A (no) |
NO (1) | NO812558L (no) |
NZ (1) | NZ197853A (no) |
PH (1) | PH17421A (no) |
PT (1) | PT73437B (no) |
SE (1) | SE460849B (no) |
YU (3) | YU185281A (no) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4689336A (en) * | 1981-01-02 | 1987-08-25 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine 2,4-diones |
GR78120B (no) * | 1982-03-01 | 1984-09-26 | Pfizer | |
US4430337A (en) | 1982-06-23 | 1984-02-07 | Pfizer Inc. | Alicyclic substituted oxazolidine-2,4-diones having hypoglycemic activity |
JPS59186916A (ja) * | 1983-04-06 | 1984-10-23 | Aiji Noda | 膵石症治療剤 |
US5130379A (en) * | 1988-03-08 | 1992-07-14 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
US4946942A (en) * | 1988-03-11 | 1990-08-07 | Bioresearch, Inc. | Urethane-protected amino acid-N-carboxyanhydrides |
US5442124A (en) * | 1989-06-30 | 1995-08-15 | Firmenich Sa | Process for the preparation of novel aromatic compounds |
WO1991007107A1 (en) * | 1989-11-13 | 1991-05-30 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
US5036079A (en) * | 1989-12-07 | 1991-07-30 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
AU646871B2 (en) * | 1990-06-07 | 1994-03-10 | Astrazeneca Uk Limited | Therapeutic heterocyclic compounds |
GB9017218D0 (en) * | 1990-08-06 | 1990-09-19 | Beecham Group Plc | Novel compounds |
KR930701420A (ko) * | 1990-08-23 | 1993-06-11 | 알렌 제이. 스피겔 | 혈당저하제로서의 하이드록시우레아 유도체 |
TW222626B (no) | 1991-07-22 | 1994-04-21 | Pfizer | |
US5498621A (en) * | 1992-05-01 | 1996-03-12 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
US5401761A (en) * | 1993-12-09 | 1995-03-28 | Pfizer, Inc. | Thiazolidinedione hypoglycemic agents |
US5925656A (en) * | 1995-04-10 | 1999-07-20 | Dr. Reddy's Research Foundation | Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
GB9604242D0 (en) | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
US5801173A (en) * | 1996-05-06 | 1998-09-01 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
ZA973850B (en) * | 1996-05-06 | 1997-12-02 | Reddy Research Foundation | Novel antidiabetic compounds having hypolipidaemic, anti-hypertensive properties, process for their preparation and pharmaceutical compositions containing them. |
ZA973848B (en) * | 1996-05-06 | 1997-12-02 | Reddy Research Foundation | Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them. |
US5919782A (en) * | 1996-05-06 | 1999-07-06 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
USRE39266E1 (en) * | 1996-07-01 | 2006-09-05 | Dr. Reddy's Laboratories, Limited | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
US5985884A (en) * | 1996-07-01 | 1999-11-16 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
US6372750B2 (en) * | 1996-07-01 | 2002-04-16 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases |
US6114526A (en) * | 1996-07-01 | 2000-09-05 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
BR9913157A (pt) * | 1998-08-21 | 2001-05-15 | Viropharma Inc | Processos para tratar ou previnir infecção causada por pelo menos um vìrus das flaviviridae e doenças associadas com a referida infecção e infecção causada por pelo menos um vìrus do gênero hepacivìrus da flaviviridade e doenças associadas com a referida infecção, composição farmacêutica para tratar ou previnir infecções virais, e, composto |
AU6331199A (en) * | 1998-09-30 | 2000-04-17 | Roche Diagnostics Gmbh | Oxazolidine derivatives for the treatment and prevention of metabolic bone disorders |
US6399640B1 (en) | 1999-06-18 | 2002-06-04 | Merck & Co., Inc. | Arylthiazolidinedione and aryloxazolidinedione derivatives |
DE60032898T2 (de) | 1999-06-18 | 2007-10-25 | Merck & Co., Inc. | Arylthiazolidindion- und aryloxazolidinderivate |
TW200901959A (en) | 2007-03-09 | 2009-01-16 | Indigene Pharmaceuticals Inc | Combination of metformin R-(+) lipoate and antihyperlipidemic agents for the treatment of diabetic hyperglycemia and diabetic complications |
JP5417860B2 (ja) * | 2008-08-26 | 2014-02-19 | 住友化学株式会社 | α−ヒドロキシエステル類の製造方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE729852C (de) * | 1939-07-06 | 1943-01-04 | Carl Nachtigall | Verfahren zur Herstellung von 2, 4-Dioxooxazolidinen |
US2338220A (en) * | 1942-01-31 | 1944-01-04 | Mallinckrodt Chemical Works | Process of making oxazolidinediones |
US2721197A (en) * | 1953-01-05 | 1955-10-18 | Bristol Lab Inc | Bicyclic lactams |
US2961377A (en) * | 1957-08-05 | 1960-11-22 | Us Vitamin Pharm Corp | Oral anti-diabetic compositions and methods |
FR1284516A (fr) * | 1957-11-20 | 1962-02-16 | France Etat | Produits utilisables notamment comme agents susceptibles d'agir sur la croissance des plantes et leur procédé de fabrication |
GB1227428A (no) * | 1968-04-08 | 1971-04-07 | ||
US3699229A (en) * | 1970-12-18 | 1972-10-17 | Abbott Lab | 2-oxo-5-phenyl-4-oxazolidinone as an anti-depressant agent |
AT322266B (de) * | 1972-11-06 | 1975-05-12 | Rath Karl Friedrich | Vorrichtung zum einsetzen von pflanzen |
FR2207706B1 (no) * | 1972-11-24 | 1975-11-28 | Orsymonde | |
DE2813873A1 (de) * | 1978-03-31 | 1979-10-11 | Basf Ag | Verfahren zur herstellung von oxazolidin-2,4-dionen |
US4200642A (en) * | 1978-08-21 | 1980-04-29 | Pfizer Inc. | Spiro-oxazolidindiones |
-
1981
- 1981-01-02 US US06/222,202 patent/US4367234A/en not_active Expired - Fee Related
- 1981-07-22 HU HU812142A patent/HU185682B/hu not_active IP Right Cessation
- 1981-07-22 GB GB8122525A patent/GB2083810B/en not_active Expired
- 1981-07-24 AR AR286202A patent/AR228061A1/es active
- 1981-07-24 DE DE19813129309 patent/DE3129309A1/de active Granted
- 1981-07-24 AT AT0328681A patent/AT376424B/de not_active IP Right Cessation
- 1981-07-24 SE SE8104542A patent/SE460849B/sv not_active IP Right Cessation
- 1981-07-27 FR FR8114543A patent/FR2487348B1/fr not_active Expired
- 1981-07-27 PH PH25969A patent/PH17421A/en unknown
- 1981-07-27 LU LU83512A patent/LU83512A1/fr unknown
- 1981-07-27 PT PT73437A patent/PT73437B/pt unknown
- 1981-07-27 FI FI812340A patent/FI77457C/fi not_active IP Right Cessation
- 1981-07-27 NO NO812558A patent/NO812558L/no unknown
- 1981-07-27 IL IL63422A patent/IL63422A/xx unknown
- 1981-07-27 CH CH4879/81A patent/CH653025A5/fr not_active IP Right Cessation
- 1981-07-27 NL NL8103536A patent/NL8103536A/nl not_active Application Discontinuation
- 1981-07-27 ES ES504322A patent/ES8306367A1/es not_active Expired
- 1981-07-27 CA CA000382586A patent/CA1155855A/en not_active Expired
- 1981-07-27 IE IE1695/81A patent/IE51427B1/en unknown
- 1981-07-27 AU AU73435/81A patent/AU526905B2/en not_active Ceased
- 1981-07-27 YU YU01852/81A patent/YU185281A/xx unknown
- 1981-07-27 IT IT23175/81A patent/IT1138110B/it active
- 1981-07-27 KR KR1019810002716A patent/KR850000381B1/ko active
- 1981-07-27 NZ NZ197853A patent/NZ197853A/en unknown
- 1981-07-27 DK DK334681A patent/DK151882C/da active
- 1981-07-27 GR GR65637A patent/GR74590B/el unknown
- 1981-07-28 DD DD81232154A patent/DD202149A5/de unknown
-
1982
- 1982-05-13 AR AR289383A patent/AR230834A1/es active
- 1982-05-13 AR AR289384A patent/AR231721A1/es active
- 1982-08-02 ES ES514665A patent/ES8306132A1/es not_active Expired
- 1982-08-02 ES ES514666A patent/ES8306133A1/es not_active Expired
-
1983
- 1983-04-18 YU YU00881/83A patent/YU88183A/xx unknown
- 1983-04-18 YU YU00882/83A patent/YU88283A/xx unknown
- 1983-06-24 GB GB08317144A patent/GB2128987B/en not_active Expired
- 1983-06-24 GB GB08317145A patent/GB2132609B/en not_active Expired
-
1984
- 1984-10-29 KR KR1019840006723A patent/KR850000382B1/ko not_active IP Right Cessation
- 1984-10-29 KR KR1019840006724A patent/KR850000387B1/ko not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SE460849B (sv) | Hypoglykemiska 5-substituerade oxazolidin-2,4-dioner | |
SU1124888A3 (ru) | Способ получени производных 5-замещенных оксазолидин-2,4-дионов в виде рацемата или оптически активного изомера в свободном виде или в виде фармацевтически приемлемой соли | |
EA012163B1 (ru) | Способ получения хиральных 8-(3-аминопиперидин-1-ил)ксантинов | |
KR20080020613A (ko) | (치환된) (r)- 또는 (s)-만델산의 동적 분할 방법 | |
JPS63275561A (ja) | 置換ピロール類 | |
US6649767B2 (en) | Process for preparing 1,4-dihydropyridine compounds | |
US5349103A (en) | Preparation of aromatic nitriles | |
JPH021478A (ja) | 二置換ピリジン類 | |
NO885117L (no) | Substituerte hydroksylaminer. | |
US3083208A (en) | 1-acyl and 1-carbalkoxy-3-pyrrolidinols | |
IL103229A (en) | History of imidazolylmethyl-pyridine, their preparation and pharmaceutical preparations containing them | |
US4448971A (en) | Hypoglycemic 5-phenyl-substituted oxazolidine-2,4-diones | |
US5990121A (en) | Use of 1,2-bridged 1,4-dihydropyridines as medicaments | |
US4407811A (en) | Hypoglycemic 5-substituted oxazolidine-2,4-diones | |
WO2019229141A1 (fr) | Procede de fabrication de composes comprenant un groupe fonctionnel oxazolopyridinones | |
CA1235706A (en) | (substituted-phenyl)-5-oxo-pyrrolidine-2-propanoic acids and derivatives as cognition activators | |
HU198915B (en) | Process for producing new 2-thiazolidinone derivatives and pharmaceutical compositions containing them | |
US4399296A (en) | Hypoglycemic 5-substituted oxazolidine-2,4-diones | |
Van Heyningen | 3-Benzoyl-4-piperidones | |
WO2006123648A1 (ja) | 3-置換チオフェンの製法 | |
HUT73432A (en) | Bicyclic substituted oxazol- and thiazol-ethers | |
EP0242950B1 (en) | Dihydropyridines, process for their preparation and their use as therapeutics | |
Allin et al. | Highly diastereoselective synthesis of 2, 3-dihydro-9bH-thiazolo [2, 3-a] isoindolin-5-ones | |
FR2586417A1 (fr) | Composes heterocycliques, leur preparation et composition pharmaceutique | |
FR2588003A1 (fr) | Derives de 1,4-dihydropyridine-sulfone, procedes de preparation de ces composes et compositions pharmaceutiques les comprenant |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
NUG | Patent has lapsed |
Ref document number: 8104542-9 Effective date: 19910117 Format of ref document f/p: F |