JPS6357588A - ヒダントイン誘導体、その塩並びに該化合物を有効成分とする糖尿病合併症の予防及び治療剤 - Google Patents
ヒダントイン誘導体、その塩並びに該化合物を有効成分とする糖尿病合併症の予防及び治療剤Info
- Publication number
- JPS6357588A JPS6357588A JP19992486A JP19992486A JPS6357588A JP S6357588 A JPS6357588 A JP S6357588A JP 19992486 A JP19992486 A JP 19992486A JP 19992486 A JP19992486 A JP 19992486A JP S6357588 A JPS6357588 A JP S6357588A
- Authority
- JP
- Japan
- Prior art keywords
- group
- imidazolidine
- dihydro
- spiro
- fluoro
- 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.)
- Granted
Links
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- 150000001469 hydantoins Chemical class 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- -1 1H-tetrazol-5-yl Chemical group 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
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- 239000001257 hydrogen Substances 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 24
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 16
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- 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 claims description 5
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- WAAPEIZFCHNLKK-SZSXPDSJSA-N (2R)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide Chemical compound FC=1C=CC2=C(C=1)C1(NC(NC1=O)=O)C[C@@H](O2)C(=O)N WAAPEIZFCHNLKK-SZSXPDSJSA-N 0.000 claims 2
- ADJOGNSGNYCKHF-OJYJAAIMSA-N (2R)-6-fluoro-2-(hydroxymethyl)spiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione Chemical compound FC=1C=CC2=C(C=1)C1(NC(NC1=O)=O)C[C@@H](O2)CO ADJOGNSGNYCKHF-OJYJAAIMSA-N 0.000 claims 2
- MUOITVAMHSVXLO-UHFFFAOYSA-N (4,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl)methanamine Chemical compound C1C(CN)C(C)C2C(C)(C)C1C2 MUOITVAMHSVXLO-UHFFFAOYSA-N 0.000 claims 2
- WAAPEIZFCHNLKK-UHFFFAOYSA-N 6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide Chemical compound C12=CC(F)=CC=C2OC(C(=O)N)CC21NC(=O)NC2=O WAAPEIZFCHNLKK-UHFFFAOYSA-N 0.000 claims 2
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- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 claims 1
- ADJOGNSGNYCKHF-UHFFFAOYSA-N 6-fluoro-2-(hydroxymethyl)spiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2OC(CO)CC21NC(=O)NC2=O ADJOGNSGNYCKHF-UHFFFAOYSA-N 0.000 claims 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims 1
- FBVCHQRZGHDPMJ-UHFFFAOYSA-N methyl 6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxylate Chemical compound C12=CC(F)=CC=C2OC(C(=O)OC)CC21NC(=O)NC2=O FBVCHQRZGHDPMJ-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 abstract description 3
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- 239000001099 ammonium carbonate Substances 0.000 abstract description 3
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- 239000000463 material Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 67
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- 239000002904 solvent Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
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- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910001424 calcium ion 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 201000007025 diabetic cataract Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 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
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19992486A JPS6357588A (ja) | 1986-08-28 | 1986-08-28 | ヒダントイン誘導体、その塩並びに該化合物を有効成分とする糖尿病合併症の予防及び治療剤 |
| EP87112497A EP0264586B1 (en) | 1986-08-28 | 1987-08-27 | Hydantoin derivatives for treating complications of diabetes |
| DE8787112497T DE3769066D1 (de) | 1986-08-28 | 1987-08-27 | Hydantoin-derivate zur behandlung von komplikationen bei diabetes. |
| US07/090,729 US4861792A (en) | 1986-08-28 | 1987-08-28 | Hydantoin derivatives for treating complications of diabetes |
| US07/355,623 US4985573A (en) | 1986-08-28 | 1989-05-23 | Hydantoin derivatives for treating complications of diabetes |
| US07/355,624 US4978758A (en) | 1986-08-28 | 1989-05-23 | Hydantoin derivatives for treating complications of diabetes |
| US07/440,135 US4985574A (en) | 1986-08-28 | 1989-11-22 | Hydantoin derivatives for treating complications of diabetes |
| US07/507,608 US5001240A (en) | 1986-08-28 | 1990-04-12 | Process for preparing optically active hydantoins |
| US08/311,005 US5447946A (en) | 1986-08-28 | 1994-09-23 | Hydantoin derivatives for treating complications of diabetes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19992486A JPS6357588A (ja) | 1986-08-28 | 1986-08-28 | ヒダントイン誘導体、その塩並びに該化合物を有効成分とする糖尿病合併症の予防及び治療剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6357588A true JPS6357588A (ja) | 1988-03-12 |
| JPH0372227B2 JPH0372227B2 (enrdf_load_stackoverflow) | 1991-11-18 |
Family
ID=16415860
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19992486A Granted JPS6357588A (ja) | 1986-08-28 | 1986-08-28 | ヒダントイン誘導体、その塩並びに該化合物を有効成分とする糖尿病合併症の予防及び治療剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6357588A (enrdf_load_stackoverflow) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63250373A (ja) * | 1987-04-08 | 1988-10-18 | Sanwa Kagaku Kenkyusho Co Ltd | （＋）―３，４―ジヒドロ―４―オキソ―２ｈ―１―ベンゾピラン―２―カルボン酸誘導体及びその製法 |
| JPH037225A (ja) * | 1989-02-22 | 1991-01-14 | Sanwa Kagaku Kenkyusho Co Ltd | アルドース還元酵素阻害作用を有し且つ吸収性の良好な薬剤組成物 |
| US5036080A (en) * | 1988-04-07 | 1991-07-30 | Sanwa Kagaku Kenyusho Co., Ltd. | (D)-6-fluoro-2,3-dihydro-2',5-dioxo-spiro[4H-1-benzopyran-4,4'-imidazolide]-2-carboxamide compounds |
| JPH049384A (ja) * | 1990-04-27 | 1992-01-14 | Sanwa Kagaku Kenkyusho Co Ltd | ヒダントイン誘導体を有効成分とする循環器系疾患の予防及び治療剤並びに循環器系疾患と糖尿病合併症の同時的予防及び治療剤 |
| WO2005079792A1 (ja) * | 2004-02-20 | 2005-09-01 | Sanwa Kagaku Kenkyusho Co., Ltd. | 重症糖尿病網膜症の予防又は治療剤 |
| WO2006090699A1 (ja) * | 2005-02-22 | 2006-08-31 | Sanwa Kagaku Kenkyusho Co., Ltd. | 虚血又は虚血再灌流によって起こる心機能障害若しくは心筋障害の予防又は治療剤 |
| WO2011136161A1 (ja) | 2010-04-28 | 2011-11-03 | 株式会社 三和化学研究所 | 内耳障害の予防又は治療薬 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5353653A (en) * | 1976-10-18 | 1978-05-16 | Pfizer | Hydantoin derivatives medicines |
| JPS53144575A (en) * | 1977-05-23 | 1978-12-15 | Pfizer | Spiroohydantoin |
| JPS5745185A (en) * | 1980-07-21 | 1982-03-13 | Eisai Co Ltd | Hydantoin derivative and its preparation |
| JPS58213717A (ja) * | 1982-01-20 | 1983-12-12 | Eisai Co Ltd | ヒダントイン誘導体を含有する治療用薬剤 |
| 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 |
-
1986
- 1986-08-28 JP JP19992486A patent/JPS6357588A/ja active Granted
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5353653A (en) * | 1976-10-18 | 1978-05-16 | Pfizer | Hydantoin derivatives medicines |
| JPS53144575A (en) * | 1977-05-23 | 1978-12-15 | Pfizer | Spiroohydantoin |
| JPS5745185A (en) * | 1980-07-21 | 1982-03-13 | Eisai Co Ltd | Hydantoin derivative and its preparation |
| JPS58213717A (ja) * | 1982-01-20 | 1983-12-12 | Eisai Co Ltd | ヒダントイン誘導体を含有する治療用薬剤 |
| 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 |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63250373A (ja) * | 1987-04-08 | 1988-10-18 | Sanwa Kagaku Kenkyusho Co Ltd | （＋）―３，４―ジヒドロ―４―オキソ―２ｈ―１―ベンゾピラン―２―カルボン酸誘導体及びその製法 |
| US5036080A (en) * | 1988-04-07 | 1991-07-30 | Sanwa Kagaku Kenyusho Co., Ltd. | (D)-6-fluoro-2,3-dihydro-2',5-dioxo-spiro[4H-1-benzopyran-4,4'-imidazolide]-2-carboxamide compounds |
| JPH037225A (ja) * | 1989-02-22 | 1991-01-14 | Sanwa Kagaku Kenkyusho Co Ltd | アルドース還元酵素阻害作用を有し且つ吸収性の良好な薬剤組成物 |
| JPH049384A (ja) * | 1990-04-27 | 1992-01-14 | Sanwa Kagaku Kenkyusho Co Ltd | ヒダントイン誘導体を有効成分とする循環器系疾患の予防及び治療剤並びに循環器系疾患と糖尿病合併症の同時的予防及び治療剤 |
| WO2005079792A1 (ja) * | 2004-02-20 | 2005-09-01 | Sanwa Kagaku Kenkyusho Co., Ltd. | 重症糖尿病網膜症の予防又は治療剤 |
| WO2006090699A1 (ja) * | 2005-02-22 | 2006-08-31 | Sanwa Kagaku Kenkyusho Co., Ltd. | 虚血又は虚血再灌流によって起こる心機能障害若しくは心筋障害の予防又は治療剤 |
| JP5022214B2 (ja) * | 2005-02-22 | 2012-09-12 | 株式会社三和化学研究所 | 虚血又は虚血再灌流によって起こる心機能障害若しくは心筋障害の予防又は治療剤 |
| WO2011136161A1 (ja) | 2010-04-28 | 2011-11-03 | 株式会社 三和化学研究所 | 内耳障害の予防又は治療薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0372227B2 (enrdf_load_stackoverflow) | 1991-11-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |