DE2933441C2 - Spiro-[4H-2,3-dihydrobenzopyran(4,5')oxazolidin]-2',4'-dione und solche Verbindungen enthaltende Arzneimittel - Google Patents
Spiro-[4H-2,3-dihydrobenzopyran(4,5')oxazolidin]-2',4'-dione und solche Verbindungen enthaltende ArzneimittelInfo
- Publication number
- DE2933441C2 DE2933441C2 DE2933441A DE2933441A DE2933441C2 DE 2933441 C2 DE2933441 C2 DE 2933441C2 DE 2933441 A DE2933441 A DE 2933441A DE 2933441 A DE2933441 A DE 2933441A DE 2933441 C2 DE2933441 C2 DE 2933441C2
- Authority
- DE
- Germany
- Prior art keywords
- spiro
- dihydrobenzopyran
- oxazolidine
- dione
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 title claims description 31
- 150000001875 compounds Chemical class 0.000 title claims description 22
- 239000003814 drug Substances 0.000 title description 2
- 239000000460 chlorine Chemical group 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 3
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000000034 method Methods 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- -1 sulfonylureas Chemical class 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 206010012601 diabetes mellitus Diseases 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003288 aldose reductase inhibitor Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 7
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000000600 sorbitol Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 241000219739 Lens Species 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 102000016912 Aldehyde Reductase Human genes 0.000 description 5
- 108010053754 Aldehyde reductase Proteins 0.000 description 5
- 208000002177 Cataract Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 4
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 230000035508 accumulation Effects 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 4
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 210000003497 sciatic nerve Anatomy 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 4
- 229960001052 streptozocin Drugs 0.000 description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000002249 Diabetes Complications Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229950005223 levamfetamine Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- KWTSXDURSIMDCE-MRVPVSSYSA-N (R)-amphetamine Chemical compound C[C@@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-MRVPVSSYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010007749 Cataract diabetic Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 201000007025 diabetic cataract Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- QAHZIGHCEBUNGT-QMGFNSACSA-N (5r,6s,7s,8r,9r)-6,7,8-trihydroxy-9-(hydroxymethyl)-1,3-diazaspiro[4.5]decane-2,4-dione Chemical class O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)C[C@]11C(=O)NC(=O)N1 QAHZIGHCEBUNGT-QMGFNSACSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- MTYHIWQZNFDCJT-UHFFFAOYSA-N 2-ethoxy-4,5-dihydro-1,3-oxazole Chemical class CCOC1=NCCO1 MTYHIWQZNFDCJT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000014647 Lens culinaris subsp culinaris Nutrition 0.000 description 1
- 244000043158 Lens esculenta Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001323 aldoses Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- GCUCIFQCGJIRNT-UHFFFAOYSA-N alrestatin Chemical compound C1=CC(C(N(CC(=O)O)C2=O)=O)=C3C2=CC=CC3=C1 GCUCIFQCGJIRNT-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical class O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Photosensitive Polymer And Photoresist Processing (AREA)
- Moulding By Coating Moulds (AREA)
- Dental Preparations (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/935,199 US4200642A (en) | 1978-08-21 | 1978-08-21 | Spiro-oxazolidindiones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2933441A1 DE2933441A1 (de) | 1980-02-28 |
| DE2933441C2 true DE2933441C2 (de) | 1987-04-23 |
Family
ID=25466700
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2933441A Expired DE2933441C2 (de) | 1978-08-21 | 1979-08-17 | Spiro-[4H-2,3-dihydrobenzopyran(4,5')oxazolidin]-2',4'-dione und solche Verbindungen enthaltende Arzneimittel |
| DE2953954A Expired DE2953954C2 (US07652168-20100126-C00068.png) | 1978-08-21 | 1979-08-17 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2953954A Expired DE2953954C2 (US07652168-20100126-C00068.png) | 1978-08-21 | 1979-08-17 |
Country Status (34)
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4329459A (en) * | 1980-05-05 | 1982-05-11 | The Upjohn Company | Tetrahydrobenzopyran derivatives |
| US4367234A (en) * | 1980-07-28 | 1983-01-04 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
| SG56656G (en) * | 1980-07-28 | 1987-03-27 | Pfizer | Hypoglycemic 5-substituted oxazolidine-2, 4-diones |
| ES8400116A1 (es) * | 1981-10-13 | 1983-10-16 | Pfizer | "un procedimiento por analogia para la preparacion de derivados de espiro-oxindol-oxazolidindiona". |
| US4438272A (en) | 1982-04-15 | 1984-03-20 | Alcon Laboratories, Inc. | Spiro-(fluoren-9,4'-imidazolidine)-2',5'-diones |
| US4540700A (en) * | 1982-04-15 | 1985-09-10 | Alcon Laboratories, Inc. | Treatment of diabetic complications with certain spiro-imidazolidine-diones |
| US4436745A (en) | 1982-04-15 | 1984-03-13 | Alcon Laboratories, Inc. | Method of inhibiting aldose reductase activity |
| US4464385A (en) * | 1982-04-15 | 1984-08-07 | Alcon Laboratories, Inc. | Treatment of diabetic complications with hydantoins |
| ZA832679B (en) * | 1982-05-07 | 1983-12-28 | Ici Plc | Indoline derivatives |
| US4430337A (en) | 1982-06-23 | 1984-02-07 | Pfizer Inc. | Alicyclic substituted oxazolidine-2,4-diones having hypoglycemic activity |
| US4556670A (en) * | 1982-12-06 | 1985-12-03 | Pfizer Inc. | Spiro-3-hetero-azolones for treatment of diabetic complications |
| US4464380A (en) * | 1983-05-25 | 1984-08-07 | Pfizer Inc. | Imidazolidinedione derivatives |
| US4533667A (en) * | 1983-05-25 | 1985-08-06 | Pfizer Inc. | Imidazolidinedione derivatives |
| DK277484A (da) * | 1983-06-23 | 1984-12-24 | Hoffmann La Roche | Thiazolidinderivater |
| JPS61200991A (ja) * | 1985-03-04 | 1986-09-05 | Sanwa Kagaku Kenkyusho:Kk | スピロ―３―ヘテロアゾリジン化合物、その製法及びそれを有効成分とする糖尿病合併症の予防及び治療剤 |
| DE3522791C1 (en) * | 1985-06-26 | 1987-01-02 | Ferroplast Gmbh | Positioning wall for lagging a cavity to be filled with a hardenable material in mining or tunnelling |
| US4853410A (en) * | 1986-01-17 | 1989-08-01 | Pfizer Inc. | Hydroxyacetic acid derivatives for the treatment of diabetic complications |
| US5039672A (en) * | 1990-04-05 | 1991-08-13 | Pfizer Inc. | Heterocyclic compounds as aldose reductase inhibitors |
| US5068332A (en) * | 1990-10-12 | 1991-11-26 | American Home Products Corporation | Alkylidene analogs of 1'-aminospiro[isoquinoline-4(1H),3'-pyrrolidine]-1,2',3,5'(2H)-tetrones useful as aldose reductase inhibitors |
| US5102886A (en) * | 1990-10-12 | 1992-04-07 | American Home Products Corporation | 1'-aminospiro[isoquinoline-4(1H),3'-pyrrolidine]-1,2',3,5'(2H)-tetrones and analogs thereof useful as aldose reductase inhibitors |
| FR2707981B1 (fr) * | 1993-07-20 | 1995-09-01 | Adir | Nouveaux dérivés de benzospiroalcène, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| CA2376919C (en) | 1999-06-18 | 2008-11-04 | Merck & Co., Inc. | Arylthiazolidinedione and aryloxazolidinedione derivatives |
| WO2000078313A1 (en) | 1999-06-18 | 2000-12-28 | Merck & Co., Inc. | Arylthiazolidinedione and aryloxazolidinedione derivatives |
| ITPI20060083A1 (it) * | 2006-07-11 | 2008-01-12 | Univ Pisa | Derivati 2,2-dimetilcromanici 4-spiro-eterocicilici azotati (a 5 e 6 termini) n-sostituiti quali cardio-protettori nei confronti dell'insulto ischemico |
| USD775790S1 (en) * | 2015-11-18 | 2017-01-10 | Ginger Damon | Motorcycle jacket |
| JP2021507767A (ja) | 2017-12-21 | 2021-02-25 | エシティ・ハイジーン・アンド・ヘルス・アクチエボラグ | 吸収性物品及び吸収性物品を製造する方法 |
| JP7150023B2 (ja) | 2017-12-21 | 2022-10-07 | エシティ・ハイジーン・アンド・ヘルス・アクチエボラグ | 吸収性物品 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1204232B (de) * | 1959-07-16 | 1965-11-04 | Ncr Co | Verfahren zur Herstellung von Derivaten von 3-Alkyl-3'-methyl-spiro[benzoxazolin-2, 2'-(2'H-1'-benzopyran)] |
| US3532744A (en) * | 1967-07-28 | 1970-10-06 | American Home Prod | 1- and 2-amino substituted indane and tetralene carboxylic acids |
| US3821383A (en) * | 1972-07-10 | 1974-06-28 | Ayerst Mckenna & Harrison | Compositions for and a method of treating diabetic complications |
| CA1088945A (en) * | 1976-10-18 | 1980-11-04 | Pfizer Limited | Hydantoin derivatives as therapeutic agents |
-
1978
- 1978-08-21 US US05/935,199 patent/US4200642A/en not_active Expired - Lifetime
-
1979
- 1979-06-20 DK DK258479A patent/DK258479A/da not_active Application Discontinuation
- 1979-06-21 IN IN451/DEL/79A patent/IN152416B/en unknown
- 1979-07-27 GB GB7926348A patent/GB2028318B/en not_active Expired
- 1979-08-16 YU YU1999/79A patent/YU41488B/xx unknown
- 1979-08-16 CH CH752879A patent/CH639974A5/fr not_active IP Right Cessation
- 1979-08-17 DE DE2933441A patent/DE2933441C2/de not_active Expired
- 1979-08-17 CA CA000333955A patent/CA1121361A/en not_active Expired
- 1979-08-17 HU HU79PI685A patent/HU179746B/hu unknown
- 1979-08-17 FI FI792567A patent/FI65255C/fi not_active IP Right Cessation
- 1979-08-17 DE DE2953954A patent/DE2953954C2/de not_active Expired
- 1979-08-18 JP JP54105459A patent/JPS6011914B2/ja not_active Expired
- 1979-08-20 EG EG79509A patent/EG14639A/xx active
- 1979-08-20 NZ NZ191350A patent/NZ191350A/en unknown
- 1979-08-20 BE BE0/196785A patent/BE878311A/fr not_active IP Right Cessation
- 1979-08-20 FR FR7920969A patent/FR2442851A1/fr active Granted
- 1979-08-20 SU SU792803649A patent/SU942597A3/ru active
- 1979-08-20 ZA ZA00794379A patent/ZA794379B/xx unknown
- 1979-08-20 IT IT25182/79A patent/IT1123536B/it active
- 1979-08-20 LU LU81613A patent/LU81613A1/fr unknown
- 1979-08-20 IE IE1592/79A patent/IE48932B1/en not_active IP Right Cessation
- 1979-08-20 ES ES483511A patent/ES483511A1/es not_active Expired
- 1979-08-20 PT PT70086A patent/PT70086A/pt unknown
- 1979-08-20 AT AT0560579A patent/AT366689B/de not_active IP Right Cessation
- 1979-08-20 AU AU50092/79A patent/AU535170B2/en not_active Ceased
- 1979-08-20 GR GR59870A patent/GR71913B/el unknown
- 1979-08-20 NO NO792699A patent/NO792699L/no unknown
- 1979-08-20 IL IL58076A patent/IL58076A/xx unknown
- 1979-08-20 SE SE7906949A patent/SE447116B/sv not_active IP Right Cessation
- 1979-08-21 NL NL7906318A patent/NL7906318A/nl active Search and Examination
- 1979-08-21 PH PH22931A patent/PH18091A/en unknown
- 1979-08-21 DD DD79215099A patent/DD146602A5/de unknown
- 1979-08-21 PL PL1979217881A patent/PL130686B1/pl unknown
- 1979-08-21 CS CS795699A patent/CS208129B2/cs unknown
- 1979-08-21 AR AR277784A patent/AR225614A1/es active
- 1979-08-27 GB GB8001161A patent/GB2033904B/en not_active Expired
- 1979-11-16 JP JP54148748A patent/JPS6011915B2/ja not_active Expired
- 1979-11-16 JP JP54148749A patent/JPS5943954B2/ja not_active Expired
- 1979-11-16 JP JP54148747A patent/JPS5946517B2/ja not_active Expired
-
1980
- 1980-02-07 FR FR8002697A patent/FR2440949A1/fr active Granted
- 1980-02-07 FR FR8002698A patent/FR2440950A1/fr active Granted
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2933441C2 (de) | Spiro-[4H-2,3-dihydrobenzopyran(4,5')oxazolidin]-2',4'-dione und solche Verbindungen enthaltende Arzneimittel | |
| DE69632152T2 (de) | N-substituierte dioxothiazolidyl-benzamid-derivate und verfahren zu ihrer herstellung | |
| DE2821966C2 (de) | Rechtsdrehendes Isomer des 6-Fluor-spiro[chroman-4,4'-imidazolidin]-2',5'-dions sowie der Basensalze hiervon und deren Verwendung | |
| DD207713A1 (de) | Substituierte imidazolabkoemmlinge, ihre herstellung und verwendung | |
| DE2759927C2 (de) | Spiro-hydantoin-Verbindungen | |
| EP0090362A2 (de) | Neue Derivate von Cycloalka(c)pyrrol-carbonsäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie neue Cycloalka(c)pyrrol-carbonsäuren als Zwischenstufen und Verfahren zu deren Herstellung | |
| DE2733868A1 (de) | Neue 1,2,4,5-tetrahydro-3h-2-benzazepin-3-one, verfahren zu ihrer herstellung und diese enthaltende arzneimittel | |
| DE2135678A1 (de) | beta agonistisch wirksame Aminver bindungen | |
| DE69018876T2 (de) | Pyridazinon-Derivate. | |
| DE69227080T2 (de) | Thiazolidin-2,4-dione, salze hiervon sowie verfahren zur herstellung | |
| DE3315106A1 (de) | Benzoazacycloalkyl-spiro-imidazolidine, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zubereitungen | |
| EP0041215A2 (de) | Imidazoazolalkensäureamide, neue Zwischenprodukte zu ihrer Herstellung, ihre Herstellung und ihre Verwendung in Arzneimitteln | |
| CH645631A5 (en) | Process for the preparation of hydantoin derivatives | |
| DE2234651A1 (de) | Eckige klammer auf 1-(p-chlorbenzoyl)5-methoxy-2-methyl-3-indol eckige klammer zu acetoxyessigsaeure, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln | |
| DE69005861T2 (de) | Benzoxepin-Derivate. | |
| DE3784835T2 (de) | Chinoxalinon-derivate. | |
| EP0749970B1 (de) | Benzisothiazolyl-substituierte Aminomethylchromane | |
| US4226875A (en) | Novel spiro-oxazolidinediones | |
| EP0082461B1 (de) | Substituierte Phenoxyalkanolamine und Phenoxyalkanol-cycloalkylamine, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende pharmazeutische Zubereitungen und Zwischenprodukte | |
| DE3102769A1 (de) | "bis-moranolinderivate" | |
| DD264215A5 (de) | Verfahren zur herstellung von spiroimidazolidinen | |
| DE1493912A1 (de) | Naphthylessigsaeuren und Verfahren zu deren Herstellung | |
| DE69526413T2 (de) | Heterocyclische Carboxyalkylderivate | |
| DE2332707A1 (de) | Tricyclische tetrahydronaphthalinderivate, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE3807813A1 (de) | Neue benzocycloheptenderivate, diese verbindungen enthaltende arzneimittel und verfahren zu deren herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OAP | Request for examination filed | ||
| OD | Request for examination | ||
| 8172 | Supplementary division/partition in: |
Ref country code: DE Ref document number: 2953953 Format of ref document f/p: P |
|
| Q171 | Divided out to: |
Ref country code: DE Ref document number: 2953953 |
|
| 8172 | Supplementary division/partition in: |
Ref country code: DE Ref document number: 2953954 Format of ref document f/p: P |
|
| Q171 | Divided out to: |
Ref country code: DE Ref document number: 2953954 |
|
| 8128 | New person/name/address of the agent |
Representative=s name: LEDERER, F., DIPL.-CHEM. DR., PAT.-ANW., 8000 MUEN |
|
| AH | Division in |
Ref country code: DE Ref document number: 2953954 Format of ref document f/p: P Ref country code: DE Ref document number: 2953953 Format of ref document f/p: P |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| AH | Division in |
Ref country code: DE Ref document number: 2953954 Format of ref document f/p: P |
|
| 8339 | Ceased/non-payment of the annual fee |