EP0000153A1 - 4-Hydroxy-2-quinolinone-3-carboxylic acids, their preparation and pharmaceutical compositions containing them. - Google Patents
4-Hydroxy-2-quinolinone-3-carboxylic acids, their preparation and pharmaceutical compositions containing them. Download PDFInfo
- Publication number
- EP0000153A1 EP0000153A1 EP78100168A EP78100168A EP0000153A1 EP 0000153 A1 EP0000153 A1 EP 0000153A1 EP 78100168 A EP78100168 A EP 78100168A EP 78100168 A EP78100168 A EP 78100168A EP 0000153 A1 EP0000153 A1 EP 0000153A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- carbon atoms
- alkyl
- formula
- compound
- hydrogen
- 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.)
- Ceased
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 230000007062 hydrolysis Effects 0.000 claims abstract 2
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- -1 6,7-methylenedioxy group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 201000009961 allergic asthma Diseases 0.000 abstract description 2
- 208000006673 asthma Diseases 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- 125000005907 alkyl ester group Chemical group 0.000 abstract 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 26
- 229960001340 histamine Drugs 0.000 description 13
- 241000700159 Rattus Species 0.000 description 8
- 239000012981 Hank's balanced salt solution Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108010058846 Ovalbumin Proteins 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 0 Cc(c(*)c1)cc(N2CC=C)c1C(O)=C(*)C2=O Chemical compound Cc(c(*)c1)cc(N2CC=C)c1C(O)=C(*)C2=O 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000001045 blue dye Substances 0.000 description 3
- 210000003630 histaminocyte Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-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 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 206010027654 Allergic conditions Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 235000001188 Peltandra virginica Nutrition 0.000 description 1
- 244000197580 Poria cocos Species 0.000 description 1
- 235000008599 Poria cocos Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920002055 compound 48/80 Polymers 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- CLPHAYNBNTVRDI-UHFFFAOYSA-N ditert-butyl propanedioate Chemical compound CC(C)(C)OC(=O)CC(=O)OC(C)(C)C CLPHAYNBNTVRDI-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910001679 gibbsite Inorganic materials 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 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
- 229960005486 vaccine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to 4-hydroxy-2-quinolinone-3-carboxylic acids and their salts.
- the invention provides pharmaceutical compositions comprising compounds of formula Ip
- the compounds of formula I p possess pharmacological activity. In particular they possess disodium chromoglycate (DSCG)-like actiivity, in particular histamine release inhibiting activity, and are therefore indicated for use in the prophylactic treatment of allergic conditions, such as allergic asthma, as indicated in the passive cutaneous anaphylaxis test in the rat.
- Female rats (180-200 g) are sensitised by subcutaneous administration of 1 mg of egg albumin (Merck Nr. 967) and 200 mg Al(OH) 3 in 1 ml of physiological saline and 0.5 ml of Haemophiluspertussis vaccine (Schwei- zerisches Serum and Impfinstitut, Bern; Nr.
- egg albumin (5 mg/ml i.v.) dissolved in physiological saline containing 0.25% Evans Blue dye (Merck Nr. 3169).
- the egg albumin elicits a cutaneous anaphylatic reaction, the intensity of which is proportional to the extent to which the Evans Blue dye diffuses into the tissue surrounding each of the four 'sensitisation sites.
- the rats are killed with ether, the underside of the skin of the back of each animal is exposed and the diameter of the areas of blue dye surrounding each of the four sensitisation sites are measured.
- Each dose of test compound is investigated in between four and six rats and the mean diameter compared with the mean value obtained in four solvent-treated control rats. The percentage inhibition is taken as the percentage of the mean diameter in the test animals relative to the mean diameter in the controls.
- the DSCG-like activity in particular histamine release inhibiting activity, can be confirmed by inhibition of histamine release fn the rat peritoneal mast cell test, basically as described by Kusner et al., J. Pharmacol. Exp. Therap. 184, 41-46 (1973), with the following modification: after sedimentation of the mast cells by centrifugation at 350 x g and 4°C, the sediments are taken up in 1 ml of Hank's balanced salt solution (HBSS) (buffered to a pH of 6.9) and pooled. The resulting suspension is centrifuged, washed again with HBSS and sedimented. The thus purified mast cells are prepared as 2 ml suspensions in HBSS.
- HBSS Hank's balanced salt solution
- the 48/80 induced histamine release minus the spontaneous histamine release is taken as 100% histamine release.
- the 48/80 induced histamine release in the presence of the test compound minus the spontaneous histamine release is then compared with the 100% value to determine the percentage inhibition by the test compound.
- the histamine determination is effected in conventional manner, for example as described in the above-mentioned Kusner et al. article, or in Kusner and Herzig, Advances in Automated Analysis, 429 (1971).
- An indicated suitable daily dosage is from 20 to 800 mg preferably administered in divided dosages of from 5 to 400 mg 2 to 4 times a day, or in retard form.
- the compounds may be used in free acid form or in the form of their pharmaceutically acceptable mono- or di-base salts, which salt forms have the same order of activity as the free acid forms.
- Suitable salts include the sodium, potassium and lithium mono- and disalts.
- the compounds of formula I may be admixed with conventional pharmaceutically acceptable diluents or carriers and, optionally, other excipients, and administered in such forms as tablets or capsules.
- novel compounds within the scope of formula I p above.
- novel compounds are those of formula I in which either
- R° are hydrogen, alkyl or alkenyl, more preferably alkyl or alkenyl, particularly allyl.
- Preferred significances of R 1 and R 2 are dialkoxy, more preferably 6,7-dialkoxy, particularly 6,7-dimethoxy. Combinations of these preferred significances are especially advantageous.
- the compounds of formula I are in the free acid or disalt form, more preferably the free acid form.
- the invention also provides a process for the preparation of compounds of formula I, characterised by hydrolysing a compound of formula II
- a suitable procedure is alkaline hydrolysis of the compound of formula II in an aqueous medium at a temperature of 40-150°C, preferably 80-120°C, followed by recovery under conditions avoiding acidification, which can lead to decarboxylation of the product.
- M is hydrogen and at least 2 mole equivalents of base are used, preferably sodium or potassium hydroxide to give the disodium or dipotassium salt.
- base preferably sodium or potassium hydroxide
- a suitable procedure is mild acid hydrolysis of a compound of formula II in which R is an acid-labile group such as t-butyl.
- the temperature is suitably from -20° to 60°C, preferably from -10° to 35°C in order to avoid decarboxylation of the product.
- Suitable acid catalysts are sulphuric acid, hydrochloric acid and perchloric acid, preferably the latter.
- the reaction medium is suitably a water-miscible non-hydroxylic organic solvent, for example acetonitrile.
- Example 1 (1-allyl-6,7-dimethoxy-4-hydroxy-7-quinolinone-3-carboxylic acid) (3.0 g) and 800 mg of sodium hydroxide are placed in 75 ml of water and the resulting suspension heated to 50°C until a solution is formed. The water is then evaporated in vacuo and the resulting residue oven dried under high vacuum to obtain 1-allyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid disodium salt, m.p. 320°C with decomposition.
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/807,914 US4187309A (en) | 1977-06-20 | 1977-06-20 | 4-Hydroxy-2-quinolinone-3-carboxylic acids and salts thereof |
| US807914 | 1977-06-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0000153A1 true EP0000153A1 (en) | 1979-01-10 |
Family
ID=25197418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP78100168A Ceased EP0000153A1 (en) | 1977-06-20 | 1978-06-15 | 4-Hydroxy-2-quinolinone-3-carboxylic acids, their preparation and pharmaceutical compositions containing them. |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4187309A (da) |
| EP (1) | EP0000153A1 (da) |
| JP (1) | JPS5495578A (da) |
| AT (1) | AT367403B (da) |
| AU (1) | AU521418B2 (da) |
| CA (1) | CA1105462A (da) |
| DK (1) | DK262678A (da) |
| ES (1) | ES470916A1 (da) |
| FI (1) | FI781885A7 (da) |
| IL (1) | IL54949A (da) |
| IT (1) | IT7849938A0 (da) |
| NZ (1) | NZ187618A (da) |
| PT (1) | PT68192B (da) |
| ZA (1) | ZA783515B (da) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0933378A1 (en) * | 1998-01-19 | 1999-08-04 | Dainippon Ink And Chemicals, Inc. | Quinolinone glycoside, production process, and anti-allergic agent |
| US7932265B2 (en) | 2004-03-31 | 2011-04-26 | Cordis Corporation | Solution formulations of sirolimus and its analogs for CAD treatment |
| US8409601B2 (en) | 2008-03-31 | 2013-04-02 | Cordis Corporation | Rapamycin coated expandable devices |
| US8420110B2 (en) | 2008-03-31 | 2013-04-16 | Cordis Corporation | Drug coated expandable devices |
| US8557272B2 (en) | 2004-03-31 | 2013-10-15 | Cordis Corporation | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE27451T1 (de) * | 1981-03-24 | 1987-06-15 | Ciba Geigy Ag | Acyl-chinolinonderivate, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische praeparate und ihre verwendung. |
| JPH07110853B2 (ja) * | 1990-09-07 | 1995-11-29 | シェリング・コーポレーション | 抗ウイルス化合物および抗高血圧化合物 |
| US5179107A (en) * | 1990-09-07 | 1993-01-12 | Schering Corporation | Antiviral quinolinone compounds |
| US5179093A (en) * | 1991-05-10 | 1993-01-12 | Schering Corporation | Quinoline-diones |
| CN119143671B (zh) * | 2024-11-21 | 2025-05-16 | 九洲药业(杭州)有限公司 | 一种插羰反应一锅法简便合成喹啉酮衍生物的方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2228488A1 (da) * | 1973-05-11 | 1974-12-06 | Ciba Geigy Ag | |
| FR2342067A1 (fr) * | 1976-02-27 | 1977-09-23 | Sandoz Sa | Medicament a base d'un derive de la quinoleine |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR814843A (fr) | 1936-12-12 | 1937-06-30 | Askania Werke Ag | Perfectionnements aux appareils cinématographiques de prise de vues |
| CH471784A (de) | 1966-01-26 | 1969-04-30 | Bayer Ag | Verfahren zur Herstellung von Carbostyrilderivaten |
| US3657223A (en) * | 1969-01-17 | 1972-04-18 | Hoffmann La Roche | Process for the preparation of benzodiazepin-2-one derivatives |
| BE806848A (fr) * | 1972-11-02 | 1974-04-30 | Sandoz Sa | Medicament a base d'un derive de la quinoleine |
| GB1480737A (en) * | 1973-10-11 | 1977-07-20 | Beecham Group Ltd | Isocoumarins thiaisocoumarins and isocarbostyrils and pharmaceutical compositions containing them |
| GB1504709A (en) | 1974-12-07 | 1978-03-22 | Fisons Ltd | N-substituted quinolinone-2-carboxyl. acid der |
| FR2340735A1 (fr) * | 1976-02-11 | 1977-09-09 | Roussel Uclaf | Nouveaux derives de l'acide 3-quinoleine carboxylique, leur procede de preparation et leur application comme medicament |
| US4119720A (en) * | 1977-07-06 | 1978-10-10 | Sandoz, Inc. | Unsaturated esters of 4-hydroxy-2-quinolinone-3-carboxylic acids and salts thereof |
-
1977
- 1977-06-20 US US05/807,914 patent/US4187309A/en not_active Expired - Lifetime
-
1978
- 1978-06-12 DK DK262678A patent/DK262678A/da not_active Application Discontinuation
- 1978-06-13 FI FI781885A patent/FI781885A7/fi not_active Application Discontinuation
- 1978-06-15 EP EP78100168A patent/EP0000153A1/en not_active Ceased
- 1978-06-19 IT IT7849938A patent/IT7849938A0/it unknown
- 1978-06-19 IL IL54949A patent/IL54949A/xx unknown
- 1978-06-19 PT PT68192A patent/PT68192B/pt unknown
- 1978-06-19 ES ES470916A patent/ES470916A1/es not_active Expired
- 1978-06-19 JP JP7332878A patent/JPS5495578A/ja active Pending
- 1978-06-19 AT AT0443078A patent/AT367403B/de not_active IP Right Cessation
- 1978-06-19 NZ NZ187618A patent/NZ187618A/xx unknown
- 1978-06-19 AU AU37251/78A patent/AU521418B2/en not_active Expired
- 1978-06-19 CA CA305,757A patent/CA1105462A/en not_active Expired
- 1978-06-20 ZA ZA783515A patent/ZA783515B/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2228488A1 (da) * | 1973-05-11 | 1974-12-06 | Ciba Geigy Ag | |
| FR2342067A1 (fr) * | 1976-02-27 | 1977-09-23 | Sandoz Sa | Medicament a base d'un derive de la quinoleine |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0933378A1 (en) * | 1998-01-19 | 1999-08-04 | Dainippon Ink And Chemicals, Inc. | Quinolinone glycoside, production process, and anti-allergic agent |
| US6242425B1 (en) | 1998-01-19 | 2001-06-05 | Dainippon Ink And Chemicals, Inc. | Quinolinone glycoside, production process, and anti-allergic agent |
| US7932265B2 (en) | 2004-03-31 | 2011-04-26 | Cordis Corporation | Solution formulations of sirolimus and its analogs for CAD treatment |
| US8557272B2 (en) | 2004-03-31 | 2013-10-15 | Cordis Corporation | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
| US8409601B2 (en) | 2008-03-31 | 2013-04-02 | Cordis Corporation | Rapamycin coated expandable devices |
| US8420110B2 (en) | 2008-03-31 | 2013-04-16 | Cordis Corporation | Drug coated expandable devices |
| US8871240B2 (en) | 2008-03-31 | 2014-10-28 | Cordis Corporation | Rapamycin coated expandable devices |
Also Published As
| Publication number | Publication date |
|---|---|
| DK262678A (da) | 1978-12-21 |
| AU3725178A (en) | 1980-01-03 |
| CA1105462A (en) | 1981-07-21 |
| ES470916A1 (es) | 1979-10-01 |
| IL54949A0 (en) | 1978-08-31 |
| AT367403B (de) | 1982-07-12 |
| ATA443078A (de) | 1981-11-15 |
| ZA783515B (en) | 1980-02-27 |
| PT68192A (en) | 1978-07-01 |
| AU521418B2 (en) | 1982-04-01 |
| JPS5495578A (en) | 1979-07-28 |
| US4187309A (en) | 1980-02-05 |
| IT7849938A0 (it) | 1978-06-19 |
| IL54949A (en) | 1982-04-30 |
| FI781885A7 (fi) | 1978-12-21 |
| NZ187618A (en) | 1981-02-11 |
| PT68192B (pt) | 1981-06-11 |
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