FI109696B - Menetelmä sydämen rytmihäiriöiden ja värinän vastaisina aineina käyttökelpoisten 4-oksosyklisten ureayhdisteiden valmistamiseksi - Google Patents
Menetelmä sydämen rytmihäiriöiden ja värinän vastaisina aineina käyttökelpoisten 4-oksosyklisten ureayhdisteiden valmistamiseksi Download PDFInfo
- Publication number
- FI109696B FI109696B FI940657A FI940657A FI109696B FI 109696 B FI109696 B FI 109696B FI 940657 A FI940657 A FI 940657A FI 940657 A FI940657 A FI 940657A FI 109696 B FI109696 B FI 109696B
- Authority
- FI
- Finland
- Prior art keywords
- methylene
- amino
- imidazolidinedione
- furanyl
- chlorophenyl
- Prior art date
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- 150000003672 ureas Chemical class 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims description 20
- 238000002360 preparation method Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 title claims description 11
- 206010003119 arrhythmia Diseases 0.000 title description 42
- 230000006793 arrhythmia Effects 0.000 title description 14
- 229940125692 cardiovascular agent Drugs 0.000 title 1
- 239000002327 cardiovascular agent Substances 0.000 title 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 title 1
- -1 CH3SO2NH Chemical group 0.000 claims abstract description 45
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- 150000003839 salts Chemical class 0.000 claims abstract description 15
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- 230000003288 anthiarrhythmic effect Effects 0.000 claims abstract description 10
- 229910052794 bromium Inorganic materials 0.000 claims abstract 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 65
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 58
- 150000001875 compounds Chemical class 0.000 claims description 37
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- MTSQDFZKIRVRAN-UHFFFAOYSA-N 1-[[5-(4-chlorophenyl)furan-2-yl]methylideneamino]-3-(8-morpholin-4-yloctyl)imidazolidine-2,4-dione Chemical compound C1=CC(Cl)=CC=C1C(O1)=CC=C1C=NN1C(=O)N(CCCCCCCCN2CCOCC2)C(=O)C1 MTSQDFZKIRVRAN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- AHYZKEDJOAXPHE-UHFFFAOYSA-N C1CN(C)CCN1CCCCN1C(=O)N(N=CC=2C=C(C)C(O)=C(C)C=2)CC1=O Chemical compound C1CN(C)CCN1CCCCN1C(=O)N(N=CC=2C=C(C)C(O)=C(C)C=2)CC1=O AHYZKEDJOAXPHE-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
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- 239000003416 antiarrhythmic agent Substances 0.000 abstract description 19
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- 125000000623 heterocyclic group Chemical group 0.000 abstract 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 3
- 125000004423 acyloxy group Chemical group 0.000 abstract 2
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- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
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- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- 150000002311 glutaric acids Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
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- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
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- 230000007574 infarction Effects 0.000 description 1
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- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
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- 239000011976 maleic acid Substances 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000010292 orthophenyl phenol Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 231100000374 pneumotoxicity Toxicity 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
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- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
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- 230000010349 pulsation Effects 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
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- 230000009467 reduction Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
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- 229940083542 sodium Drugs 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
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- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- IHCDKJZZFOUARO-UHFFFAOYSA-M sulfacetamide sodium Chemical compound O.[Na+].CC(=O)[N-]S(=O)(=O)C1=CC=C(N)C=C1 IHCDKJZZFOUARO-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000006794 tachycardia Effects 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
- 230000036962 time dependent Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
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- 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
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/80—Two oxygen atoms, e.g. hydantoin with hetero atoms or acyl radicals directly attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth 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)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US74486791A | 1991-08-14 | 1991-08-14 | |
US74486791 | 1991-08-14 | ||
PCT/US1992/006684 WO1993004061A1 (en) | 1991-08-14 | 1992-08-10 | Novel 4-oxocyclic ureas useful as antiarrhythmic and antifibrillatory agents |
US9206684 | 1992-08-10 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI940657A FI940657A (fi) | 1994-02-11 |
FI940657A0 FI940657A0 (fi) | 1994-02-11 |
FI109696B true FI109696B (fi) | 2002-09-30 |
Family
ID=24994275
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI940657A FI109696B (fi) | 1991-08-14 | 1994-02-11 | Menetelmä sydämen rytmihäiriöiden ja värinän vastaisina aineina käyttökelpoisten 4-oksosyklisten ureayhdisteiden valmistamiseksi |
Country Status (27)
Country | Link |
---|---|
US (1) | US5462940A (ja) |
EP (2) | EP0598061B1 (ja) |
JP (1) | JP3040473B2 (ja) |
KR (2) | KR100273605B1 (ja) |
AT (1) | ATE220675T1 (ja) |
AU (1) | AU668360B2 (ja) |
BR (1) | BR9206369A (ja) |
CA (1) | CA2115427C (ja) |
CZ (1) | CZ282368B6 (ja) |
DE (1) | DE69232681T2 (ja) |
DK (1) | DK0598061T3 (ja) |
ES (1) | ES2180537T3 (ja) |
FI (1) | FI109696B (ja) |
HK (1) | HK1048806A1 (ja) |
HU (1) | HU221317B1 (ja) |
IL (1) | IL102793A (ja) |
MX (1) | MX9204730A (ja) |
MY (1) | MY109205A (ja) |
NO (5) | NO306676B1 (ja) |
NZ (1) | NZ243938A (ja) |
PH (1) | PH31451A (ja) |
PL (2) | PL170984B1 (ja) |
PT (1) | PT100777B (ja) |
RU (2) | RU2221788C2 (ja) |
SK (1) | SK282656B6 (ja) |
TW (1) | TW232691B (ja) |
WO (1) | WO1993004061A1 (ja) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6083945A (en) * | 1995-06-07 | 2000-07-04 | The Procter & Gamble Company | Cyclic ureas useful as antiarrhythmic and antifibrillatory agents |
US6262068B1 (en) | 1997-02-21 | 2001-07-17 | Bristol-Myers Squibb Company | Lactam derivatives as antiarrhythmic agents |
US6048877A (en) * | 1997-02-21 | 2000-04-11 | Bristol-Myers Squibb Company | Tetralone derivatives as antiarrhythmic agents |
WO1998037068A1 (en) | 1997-02-21 | 1998-08-27 | Bristol-Myers Squibb Company | Benzoic acid derivatives and related compounds as antiarrhythmic agents |
US6664250B2 (en) | 1998-01-20 | 2003-12-16 | Bristol-Myers Squibb Co. | Lactam derivatives as antiarrhythmic agents |
EP1056726A1 (en) | 1998-02-20 | 2000-12-06 | The Procter & Gamble Company | Solid phase synthesis of 1-aminohydantoins |
CN1298403A (zh) | 1998-04-29 | 2001-06-06 | 宝洁公司 | 1,3-二取代-4-氧代环状脲的制备方法 |
US6420568B1 (en) * | 1998-04-29 | 2002-07-16 | The Procter & Gamble Company | Process for making 1,3-disubstituted-4-oxocyclic ureas |
CN100443473C (zh) * | 2005-04-30 | 2008-12-17 | 中国药科大学 | 1-氨基-3-(氮杂环基烷基)-2,4-咪唑二酮的合成方法 |
DE602006014186D1 (de) * | 2005-10-18 | 2010-06-17 | Seoul Nat Univ Ind Foundation | Verfahren zur herstellung eines rekombinanten peptids aus spinnengift, und das peptid enthaltende analgetische zusammensetzung |
TW200840578A (en) * | 2006-12-15 | 2008-10-16 | Procter & Gamble | Compositions of azimilide dihydrochloride |
US20120178762A1 (en) | 2006-12-15 | 2012-07-12 | Warner Chilcott Company, Llc | Compositions of azimilide dihydrochloride |
CN101735203B (zh) * | 2009-12-17 | 2012-05-23 | 天津药物研究院 | 盐酸阿齐利特的晶型ⅱ及其制备方法和用途 |
CN101735205B (zh) * | 2009-12-17 | 2013-05-15 | 天津药物研究院 | 盐酸阿齐利特的晶型ⅴ及其制备方法和用途 |
CN101735202B (zh) * | 2009-12-17 | 2012-05-30 | 天津药物研究院 | 盐酸阿齐利特的晶型ⅰ及其制备方法和用途 |
Family Cites Families (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB939941A (en) * | 1959-04-14 | 1963-10-16 | Norwich Pharma Co | Improvements in or relating to the manufacture of derivatives of 5-nitrofuran |
US3182058A (en) * | 1960-10-31 | 1965-05-04 | Pfizer & Co C | Nitrofuran derivatives |
DE1202281B (de) * | 1960-11-21 | 1965-10-07 | Josef Klosa Dipl Chem Dr | Verfahren zur Herstellung von N-(5-Nitro-2-furfuryliden)-1-aminohydantoinen |
NL272950A (ja) * | 1960-12-27 | |||
NL272958A (ja) * | 1960-12-27 | |||
NL272957A (ja) * | 1960-12-27 | 1900-01-01 | ||
FR1310188A (ja) * | 1960-12-27 | 1963-03-06 | ||
DE1201845B (de) * | 1962-07-14 | 1965-09-30 | Zambon Spa | Verfahren zur Herstellung von N-(5-Nitro-2-furfuryliden)-1-aminohydantoin |
NL300307A (ja) * | 1963-06-10 | |||
US3415821A (en) * | 1965-09-07 | 1968-12-10 | Norwich Pharma Co | 1-(5-substituted)furfurylideneamino hydantoins and imidazolidinones |
NL6900631A (ja) * | 1968-01-26 | 1969-07-29 | ||
JPS5032271B2 (ja) * | 1973-06-06 | 1975-10-18 | ||
US4001222A (en) * | 1975-10-14 | 1977-01-04 | Morton-Norwich Products, Inc. | 3-(Aminoacyl)-1-{[5-(substituted phenyl)furfurylidene]amino}hydantoins and process for their preparation thereof |
US4775670A (en) * | 1980-09-29 | 1988-10-04 | E. R. Squibb & Sons, Inc. | 2-oxo-1-azetidinesulfonic acid salts |
US4393204A (en) * | 1982-05-21 | 1983-07-12 | Norwich Eaton Pharmaceuticals, Inc. | 3-[[5-(4-Chlorophenyl)furfurylidene]amino]-5-(substituted)-2-oxazolidinones |
JPS5913780A (ja) * | 1982-07-13 | 1984-01-24 | Takeda Chem Ind Ltd | フルオロウラシル誘導体および抗腫瘍剤 |
US4543359A (en) * | 1982-10-01 | 1985-09-24 | Eaton Laboratories, Inc. | Treating cardiac arrhythmias with dantrolene sodium |
FR2539412B1 (fr) * | 1983-01-13 | 1986-02-21 | Shoichiro Ozaki | Derives du 5-fluoruracile et leurs utilisations therapeutiques en tant qu'agents carcinostatiques |
US4705799A (en) * | 1983-06-07 | 1987-11-10 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl benzenes useful as antibacterial agents |
US4581370A (en) * | 1983-07-12 | 1986-04-08 | Schering A.G. | Antiarrhythmic imidazoliums |
US4720580A (en) * | 1984-09-21 | 1988-01-19 | American Home Products Corporation | N-(aminoalkylene)benzenesulfonamides |
US4713382A (en) * | 1985-05-30 | 1987-12-15 | Syntex (U.S.A.) Inc. | N-phenyl-4-phenyl-1-piperazinecarboxamidines and related compounds as antiarrhythmic agents |
US4707499A (en) * | 1985-12-02 | 1987-11-17 | G. D. Searle & Co. | 3-alkyl-5-(substituted amino)methyl)dihydro-3-phenyl-2(3H)-furanones and imino analogs thereof used for treatment of arrhythmia |
GB8603120D0 (en) * | 1986-02-07 | 1986-03-12 | Pfizer Ltd | Anti-dysrhythmia agents |
PH23283A (en) * | 1986-02-26 | 1989-06-30 | Eisai Co Ltd | Piperidine derivative, pharmaceutical composition containing the same and method of use thereof |
US4804662A (en) * | 1987-05-05 | 1989-02-14 | Schering A.G. | Substituted 4-(1H-imidazol-1-yl)benzamides as antiarrhythmic agents |
US4851526A (en) * | 1987-09-04 | 1989-07-25 | Schering A.G. | 1-(4-Substituted phenyl)-1H-imidazoles compounds |
US4870095A (en) * | 1988-06-13 | 1989-09-26 | Sterling Drug, Inc. | 1H-pyrazole-1-alkanamides, antiarrhythmic compositions and use |
EP0347733A1 (en) * | 1988-06-20 | 1989-12-27 | Eisai Co., Ltd. | Optically active hydantoin derivatives |
CA2020813C (en) * | 1989-07-25 | 1995-08-01 | Frederick Dana Cazer | Nitrofurantoin crystals |
US4966967A (en) * | 1989-09-15 | 1990-10-30 | Berlex Laboratories, Inc. | 3,4,5,6-tetrahydro-2H-1,7,4-benzodioxazonines as cardiovascular agents |
US5032598A (en) * | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Nitrogens containing heterocyclic compounds as class III antiarrhythmic agents |
US4994459A (en) * | 1989-12-11 | 1991-02-19 | American Home Products Corporation | Aryloxypropane substituted piperazine derivatives with antiarrhythmic and antifibrillatory activity |
US4963561A (en) * | 1990-02-28 | 1990-10-16 | Sterling Drug Inc. | Imidazopyridines, their preparation and use |
BR9206353A (pt) * | 1991-08-14 | 1995-11-07 | Procter & Gamble Pharma | Uretanos cíclicos utilizáveis como agentes antiarrítmicos e antifibrilatórios |
BR9206371A (pt) * | 1991-08-14 | 1995-10-17 | Procter & Gamble Pharma | Novas uréias cíclicas utilzáveis como agentes antirrítmicos e antifibrilatórios |
-
1992
- 1992-08-10 EP EP92918467A patent/EP0598061B1/en not_active Expired - Lifetime
- 1992-08-10 EP EP02075117A patent/EP1231208A3/en not_active Withdrawn
- 1992-08-10 SK SK171-94A patent/SK282656B6/sk not_active IP Right Cessation
- 1992-08-10 AU AU24717/92A patent/AU668360B2/en not_active Expired
- 1992-08-10 AT AT92918467T patent/ATE220675T1/de active
- 1992-08-10 CA CA002115427A patent/CA2115427C/en not_active Expired - Lifetime
- 1992-08-10 BR BR9206369A patent/BR9206369A/pt not_active Application Discontinuation
- 1992-08-10 KR KR1019940700427A patent/KR100273605B1/ko not_active IP Right Cessation
- 1992-08-10 WO PCT/US1992/006684 patent/WO1993004061A1/en active IP Right Grant
- 1992-08-10 RU RU99101341/04A patent/RU2221788C2/ru not_active IP Right Cessation
- 1992-08-10 HU HU9400396A patent/HU221317B1/hu unknown
- 1992-08-10 PL PL92314009A patent/PL170984B1/pl unknown
- 1992-08-10 JP JP5504376A patent/JP3040473B2/ja not_active Expired - Fee Related
- 1992-08-10 DK DK92918467T patent/DK0598061T3/da active
- 1992-08-10 RU RU94015844A patent/RU2130935C1/ru not_active IP Right Cessation
- 1992-08-10 CZ CZ94306A patent/CZ282368B6/cs not_active IP Right Cessation
- 1992-08-10 PL PL92302377A patent/PL170961B1/pl unknown
- 1992-08-10 DE DE69232681T patent/DE69232681T2/de not_active Expired - Lifetime
- 1992-08-10 ES ES92918467T patent/ES2180537T3/es not_active Expired - Lifetime
- 1992-08-12 PH PH44800A patent/PH31451A/en unknown
- 1992-08-12 IL IL10279392A patent/IL102793A/en not_active IP Right Cessation
- 1992-08-13 NZ NZ243938A patent/NZ243938A/en unknown
- 1992-08-14 MY MYPI92001463A patent/MY109205A/en unknown
- 1992-08-14 PT PT100777A patent/PT100777B/pt not_active IP Right Cessation
- 1992-08-14 MX MX9204730A patent/MX9204730A/es unknown
- 1992-08-22 TW TW081106647A patent/TW232691B/zh not_active IP Right Cessation
-
1994
- 1994-02-11 FI FI940657A patent/FI109696B/fi not_active IP Right Cessation
- 1994-02-14 NO NO940497A patent/NO306676B1/no not_active IP Right Cessation
- 1994-06-03 US US08/275,461 patent/US5462940A/en not_active Expired - Lifetime
-
1999
- 1999-06-14 NO NO19992898A patent/NO310145B1/no not_active IP Right Cessation
- 1999-06-14 NO NO19992900A patent/NO310147B1/no not_active IP Right Cessation
- 1999-06-14 NO NO19992897A patent/NO310148B1/no not_active IP Right Cessation
- 1999-06-14 NO NO19992899A patent/NO310146B1/no not_active IP Right Cessation
- 1999-11-01 KR KR1019997010110A patent/KR100295946B1/ko not_active IP Right Cessation
-
2003
- 2003-01-30 HK HK03100753.4A patent/HK1048806A1/zh unknown
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