NO862123L - Fremgangsmaate for fremstilling av terapeutisk aktive spiroimidazolidiner. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive spiroimidazolidiner.Info
- Publication number
- NO862123L NO862123L NO862123A NO862123A NO862123L NO 862123 L NO862123 L NO 862123L NO 862123 A NO862123 A NO 862123A NO 862123 A NO862123 A NO 862123A NO 862123 L NO862123 L NO 862123L
- Authority
- NO
- Norway
- Prior art keywords
- imidazolidine
- formula
- compound
- mol
- reaction
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title description 10
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 239000000460 chlorine Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- 229940071870 hydroiodic acid Drugs 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims 4
- 229910015900 BF3 Inorganic materials 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- -1 chloro, methyl Chemical group 0.000 abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 11
- 150000003839 salts Chemical class 0.000 abstract description 11
- 230000001684 chronic effect Effects 0.000 abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 230000009102 absorption Effects 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical compound N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 description 6
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 6
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- 241000700159 Rattus Species 0.000 description 6
- 239000001099 ammonium carbonate Substances 0.000 description 6
- 235000012501 ammonium carbonate Nutrition 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 206010007749 Cataract diabetic Diseases 0.000 description 5
- 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 5
- 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 5
- 201000007025 diabetic cataract Diseases 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- NZNUMNLHZBSSJW-UHFFFAOYSA-N 2-(2,5-dioxo-4-phenylimidazolidin-4-yl)acetic acid Chemical compound C=1C=CC=CC=1C1(CC(=O)O)NC(=O)NC1=O NZNUMNLHZBSSJW-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- 208000002177 Cataract Diseases 0.000 description 4
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000003288 aldose reductase inhibitor Substances 0.000 description 4
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000002997 ophthalmic solution Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 150000003413 spiro compounds Chemical class 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- OVFAVWPWJBQNSE-UHFFFAOYSA-N 2-[4-(3-fluorophenyl)-2,5-dioxoimidazolidin-4-yl]acetic acid Chemical compound C=1C=CC(F)=CC=1C1(CC(=O)O)NC(=O)NC1=O OVFAVWPWJBQNSE-UHFFFAOYSA-N 0.000 description 3
- IPPYLDGVMKYNPQ-UHFFFAOYSA-N 6-fluorospiro[3h-chromene-4,5'-imidazolidine]-2,2',4'-trione Chemical compound C12=CC(F)=CC=C2OC(=O)CC21NC(=O)NC2=O IPPYLDGVMKYNPQ-UHFFFAOYSA-N 0.000 description 3
- 102000016912 Aldehyde Reductase Human genes 0.000 description 3
- 108010053754 Aldehyde reductase Proteins 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 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
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000003085 diluting agent Substances 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
- 235000011187 glycerol Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 description 2
- DWPLEOPKBWNPQV-UHFFFAOYSA-N 1-(2-methoxyphenyl)ethanone Chemical compound COC1=CC=CC=C1C(C)=O DWPLEOPKBWNPQV-UHFFFAOYSA-N 0.000 description 2
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 2
- OAHPUGHSCHLGFJ-UHFFFAOYSA-N 6-chlorospiro[3h-chromene-4,5'-imidazolidine]-2,2',4'-trione Chemical compound C12=CC(Cl)=CC=C2OC(=O)CC21NC(=O)NC2=O OAHPUGHSCHLGFJ-UHFFFAOYSA-N 0.000 description 2
- VKXPNNWTBFLAIC-UHFFFAOYSA-N 7-fluorospiro[2h-naphthalene-1,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2C=CCC21NC(=O)NC2=O VKXPNNWTBFLAIC-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
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- 239000012267 brine Substances 0.000 description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000008395 clarifying agent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940119744 dextran 40 Drugs 0.000 description 2
- 229940119743 dextran 70 Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
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- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 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
- 239000000463 material Substances 0.000 description 2
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- 238000007911 parenteral administration Methods 0.000 description 2
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- 229910052700 potassium Inorganic materials 0.000 description 2
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- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- GELNCBISSFJAHO-UHFFFAOYSA-N spiro[2h-naphthalene-1,5'-imidazolidine]-2',4'-dione Chemical compound N1C(=O)NC(=O)C11C2=CC=CC=C2C=CC1 GELNCBISSFJAHO-UHFFFAOYSA-N 0.000 description 2
- WTDIFVOMMLZEKJ-UHFFFAOYSA-N spiro[3h-chromene-4,5'-imidazolidine]-2,2',4'-trione Chemical compound N1C(=O)NC(=O)C11C2=CC=CC=C2OC(=O)C1 WTDIFVOMMLZEKJ-UHFFFAOYSA-N 0.000 description 2
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- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- KZMZPNIZGCMWGG-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-methoxyethanone Chemical compound COCC(=O)C1=CC=CC=C1Cl KZMZPNIZGCMWGG-UHFFFAOYSA-N 0.000 description 1
- SSPRAACQWRLZDF-UHFFFAOYSA-N 2-[4-(3-methoxyphenyl)-2,5-dioxoimidazolidin-4-yl]acetic acid Chemical compound COC1=CC=CC(C2(CC(O)=O)C(NC(=O)N2)=O)=C1 SSPRAACQWRLZDF-UHFFFAOYSA-N 0.000 description 1
- HDZMORWEJKLUMA-UHFFFAOYSA-N 2-[4-(3-methylphenyl)-2,5-dioxoimidazolidin-4-yl]acetic acid Chemical compound CC1=CC=CC(C2(CC(O)=O)C(NC(=O)N2)=O)=C1 HDZMORWEJKLUMA-UHFFFAOYSA-N 0.000 description 1
- GGOUKXJLOUNPFF-UHFFFAOYSA-N 2-methoxy-1-(2-methylphenyl)ethanone Chemical compound COCC(=O)C1=CC=CC=C1C GGOUKXJLOUNPFF-UHFFFAOYSA-N 0.000 description 1
- VNCQTTDYACAVDT-UHFFFAOYSA-N 2-methyl-3-oxo-3-phenylpropanoic acid Chemical class OC(=O)C(C)C(=O)C1=CC=CC=C1 VNCQTTDYACAVDT-UHFFFAOYSA-N 0.000 description 1
- QRPFBMZLGJGHGD-UHFFFAOYSA-N 4-(3-chlorophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC(Cl)=C1 QRPFBMZLGJGHGD-UHFFFAOYSA-N 0.000 description 1
- HHVYNFFVNGZSNG-UHFFFAOYSA-N 4-(3-fluorophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC(F)=C1 HHVYNFFVNGZSNG-UHFFFAOYSA-N 0.000 description 1
- SSCUVWXLQOWZAW-UHFFFAOYSA-N 6-fluoro-2-hydroxyspiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2OC(O)CC21NC(=O)NC2=O SSCUVWXLQOWZAW-UHFFFAOYSA-N 0.000 description 1
- JAIOJJBHZSQNLY-UHFFFAOYSA-N 6-methylspiro[1,3-dihydronaphthalene-4,5'-imidazolidine]-2,2',4'-trione Chemical compound C12=CC(C)=CC=C2CC(=O)CC21NC(=O)NC2=O JAIOJJBHZSQNLY-UHFFFAOYSA-N 0.000 description 1
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- 229940039717 lanolin Drugs 0.000 description 1
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- 239000007788 liquid Substances 0.000 description 1
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- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
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- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- 239000008159 sesame oil Substances 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 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
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- ZWCXEUXYVGCSIW-UHFFFAOYSA-N spiro[1,3-dihydronaphthalene-4,5'-imidazolidine]-2,2',4'-trione Chemical compound N1C(=O)NC(=O)C11C2=CC=CC=C2CC(=O)C1 ZWCXEUXYVGCSIW-UHFFFAOYSA-N 0.000 description 1
- DWWPCSYDAFOPSK-UHFFFAOYSA-N spiro[1,3-dihydroquinoline-4,5'-imidazolidine]-2,2',4'-trione Chemical compound N1C(=O)NC(=O)C11C2=CC=CC=C2NC(=O)C1 DWWPCSYDAFOPSK-UHFFFAOYSA-N 0.000 description 1
- BCORIAMJYXYJLN-UHFFFAOYSA-N spiro[2h-indene-3,5'-imidazolidine]-1,2',4'-trione Chemical compound N1C(=O)NC(=O)C11C2=CC=CC=C2C(=O)C1 BCORIAMJYXYJLN-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 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 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance 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
- 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
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 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
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 1
- 229960004224 tyloxapol Drugs 0.000 description 1
- 238000004148 unit process Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/738,924 US4575507A (en) | 1985-05-29 | 1985-05-29 | Spiro-imidazolidines as aldose reductase inhibitors and their pharmaceutical use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO862123L true NO862123L (no) | 1986-12-01 |
Family
ID=24970055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO862123A NO862123L (no) | 1985-05-29 | 1986-05-28 | Fremgangsmaate for fremstilling av terapeutisk aktive spiroimidazolidiner. |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4575507A (pt) |
| EP (1) | EP0203791B1 (pt) |
| JP (1) | JPS61277671A (pt) |
| KR (1) | KR890001548B1 (pt) |
| AT (1) | ATE46332T1 (pt) |
| AU (1) | AU560429B2 (pt) |
| DD (5) | DD264214A5 (pt) |
| DE (1) | DE3665584D1 (pt) |
| DK (1) | DK248886A (pt) |
| EG (1) | EG17859A (pt) |
| ES (2) | ES8800228A1 (pt) |
| FI (1) | FI862251A (pt) |
| GR (1) | GR861388B (pt) |
| HU (4) | HU199845B (pt) |
| IL (1) | IL78954A (pt) |
| NO (1) | NO862123L (pt) |
| NZ (1) | NZ216334A (pt) |
| PH (1) | PH22213A (pt) |
| PL (5) | PL146020B1 (pt) |
| PT (1) | PT82650B (pt) |
| ZA (1) | ZA863934B (pt) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU198212B (en) * | 1984-07-20 | 1989-08-28 | Pfizer | Process for production of spiro-imidasolones |
| US4762839A (en) * | 1985-06-06 | 1988-08-09 | Tanabe Seiyaku Co., Ltd. | Quinazolinone copmpounds useful for the prophyloxis and treatment of diabetic complications |
| JPS63132889A (ja) * | 1986-11-21 | 1988-06-04 | Tanabe Seiyaku Co Ltd | キナゾリノン誘導体 |
| EP0306525A4 (en) * | 1987-03-20 | 1991-04-24 | Alcon Laboratories Inc | Use of aldose reductase inhibitors to enhance insulin sensitivity in diabetes mellitus |
| US5202339A (en) * | 1987-08-28 | 1993-04-13 | Mochida Pharmaceutical Co., Ltd. | Hydantoin derivatives |
| US5004751A (en) * | 1987-08-28 | 1991-04-02 | Mochida Pharmaceutical Co., Ltd. | Hydantoin derivatives |
| AU623676B2 (en) * | 1988-08-24 | 1992-05-21 | Mochida Pharmaceutical Co., Ltd. | Hydantoin derivatives |
| 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 |
| US8326636B2 (en) * | 2008-01-16 | 2012-12-04 | Canyon Ip Holdings Llc | Using a physical phenomenon detector to control operation of a speech recognition engine |
| WO2013117568A1 (de) * | 2012-02-09 | 2013-08-15 | Boehringer Ingelheim International Gmbh | Verfahren zur stereoselektiven synthese von 1,4-geschützten 9-hydroxy-5-oxo-1,4-diaza-spiro [5.5] undecane |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1088945A (en) * | 1976-10-18 | 1980-11-04 | Pfizer Limited | Hydantoin derivatives as therapeutic agents |
| US4117230A (en) | 1976-10-18 | 1978-09-26 | Pfizer Inc. | Hydantoin derivatives as therapeutic agents |
| US4235911A (en) * | 1979-06-13 | 1980-11-25 | Pfizer Inc. | Hydantoin derivatives |
| US4248882A (en) * | 1980-02-12 | 1981-02-03 | Pfizer Inc. | Treating diabetes-associated complications with hydantoin amines |
| JPS5745185A (en) * | 1980-07-21 | 1982-03-13 | Eisai Co Ltd | Hydantoin derivative and its preparation |
| DE3367103D1 (en) * | 1982-11-10 | 1986-11-27 | Pfizer | Sorbinil by optical resolution with aminopinane derivatives |
| SU1380610A3 (ru) * | 1982-12-06 | 1988-03-07 | Пфайзер Инк. (Фирма) | Способ получени спирогетероазолидиндионов или их фармацевтически приемлемых солей |
| US4556670A (en) | 1982-12-06 | 1985-12-03 | Pfizer Inc. | Spiro-3-hetero-azolones for treatment of diabetic complications |
| EP0159143B1 (en) * | 1984-03-23 | 1987-12-16 | Pfizer Inc. | Spiro-indenes and spiro-1,2-dihydro-naphthalenes for treatment of diabetic complications |
| US4762838A (en) | 1985-08-30 | 1988-08-09 | Pfizer Inc. | Quinazolin-4(3H)-one derivatives as anticoccidial agents |
-
1985
- 1985-05-29 US US06/738,924 patent/US4575507A/en not_active Expired - Lifetime
-
1986
- 1986-05-23 DE DE8686303925T patent/DE3665584D1/de not_active Expired
- 1986-05-23 AT AT86303925T patent/ATE46332T1/de not_active IP Right Cessation
- 1986-05-23 EP EP86303925A patent/EP0203791B1/en not_active Expired
- 1986-05-27 ZA ZA863934A patent/ZA863934B/xx unknown
- 1986-05-27 PT PT82650A patent/PT82650B/pt not_active IP Right Cessation
- 1986-05-27 DD DD86309079A patent/DD264214A5/de not_active IP Right Cessation
- 1986-05-27 DD DD86290626A patent/DD251972A5/de not_active IP Right Cessation
- 1986-05-27 DD DD86309080A patent/DD264215A5/de not_active IP Right Cessation
- 1986-05-27 PL PL1986259739A patent/PL146020B1/pl unknown
- 1986-05-27 PL PL1986266363A patent/PL147397B1/pl unknown
- 1986-05-27 PL PL1986266365A patent/PL147399B1/pl unknown
- 1986-05-27 ES ES555375A patent/ES8800228A1/es not_active Expired
- 1986-05-27 PL PL1986266366A patent/PL147400B1/pl unknown
- 1986-05-27 PL PL1986266364A patent/PL147398B1/pl unknown
- 1986-05-27 DD DD86309078A patent/DD264213A5/de not_active IP Right Cessation
- 1986-05-28 DK DK248886A patent/DK248886A/da not_active Application Discontinuation
- 1986-05-28 NO NO862123A patent/NO862123L/no unknown
- 1986-05-28 HU HU893124A patent/HU199845B/hu unknown
- 1986-05-28 GR GR861388A patent/GR861388B/el unknown
- 1986-05-28 KR KR8604182A patent/KR890001548B1/ko not_active IP Right Cessation
- 1986-05-28 HU HU862249A patent/HU196060B/hu unknown
- 1986-05-28 NZ NZ216334A patent/NZ216334A/xx unknown
- 1986-05-28 EG EG317/86A patent/EG17859A/xx active
- 1986-05-28 FI FI862251A patent/FI862251A/fi not_active Application Discontinuation
- 1986-05-28 HU HU872418A patent/HUT49879A/hu unknown
- 1986-05-28 AU AU58012/86A patent/AU560429B2/en not_active Ceased
- 1986-05-28 IL IL78954A patent/IL78954A/xx unknown
- 1986-05-29 PH PH33830A patent/PH22213A/en unknown
- 1986-05-29 JP JP61124608A patent/JPS61277671A/ja active Pending
-
1987
- 1987-02-13 ES ES557391A patent/ES8801830A1/es not_active Expired
- 1987-05-28 HU HU893127A patent/HU893127D0/hu unknown
- 1987-11-16 DD DD87309077A patent/DD273258A5/de not_active IP Right Cessation
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