US3189598A - Fatty acid esters of riboflavin - Google Patents
Fatty acid esters of riboflavin Download PDFInfo
- Publication number
- US3189598A US3189598A US186327A US18632762A US3189598A US 3189598 A US3189598 A US 3189598A US 186327 A US186327 A US 186327A US 18632762 A US18632762 A US 18632762A US 3189598 A US3189598 A US 3189598A
- Authority
- US
- United States
- Prior art keywords
- riboflavin
- fatty acid
- acid esters
- mixture
- ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 title description 72
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 title description 35
- 229960002477 riboflavin Drugs 0.000 title description 35
- 235000019192 riboflavin Nutrition 0.000 title description 35
- 239000002151 riboflavin Substances 0.000 title description 35
- -1 Fatty acid esters Chemical class 0.000 title description 11
- 235000014113 dietary fatty acids Nutrition 0.000 title description 7
- 239000000194 fatty acid Substances 0.000 title description 7
- 229930195729 fatty acid Natural products 0.000 title description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- CNDHHGUSRIZDSL-UHFFFAOYSA-N 1-chlorooctane Chemical group CCCCCCCCCl CNDHHGUSRIZDSL-UHFFFAOYSA-N 0.000 description 3
- 229930003270 Vitamin B Natural products 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- JEIJBKDXJPNHGD-UHFFFAOYSA-N chloroform;pyridine Chemical compound ClC(Cl)Cl.C1=CC=NC=C1 JEIJBKDXJPNHGD-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 235000019156 vitamin B Nutrition 0.000 description 3
- 239000011720 vitamin B Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 230000002183 duodenal effect Effects 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- KPDQZGKJTJRBGU-UHFFFAOYSA-N lumiflavin Chemical compound CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O KPDQZGKJTJRBGU-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003287 riboflavins Chemical class 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010047612 Vitamin B2 deficiency Diseases 0.000 description 1
- 206010047623 Vitamin C deficiency Diseases 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 201000007590 ariboflavinosis Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000002795 fluorescence method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 208000004223 riboflavin deficiency Diseases 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 208000010233 scurvy Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
- C07D475/14—Benz [g] pteridines, e.g. riboflavin
Definitions
- This invention relates to fatty acid esters'of riboflavin and to a process for preparing same.
- riboflavin is a slightly water-soluble vitamin and, therefore, has some inconveniences for food-enrichment or pharmaceutical fields.
- riboflavin may be rendered fat-soluble by esterification with fatty acids.
- a fatty acid ester of riboflavin can be prepared by reacting riboflavin with an alkanoyl halide having 4 to 20 carbon atoms. The reaction may be carried out in an inert solvent, such as benzene, chloroform or other halogenated hydrocarbons, in the presence of an acid acceptor such as pyridine. Since riboflavin has four free hydroxy groups in the molecule, it is preferable to use more than four moles of the alkanoyl halide per mole of riboflavin.
- alkanoyl halide I prefer to use those having 4 to 20 carbon atoms such as butyryl, hexanoyl, octanoyl, capryl, lauroyl, myristoyl, palmitoyl and stearoyl chloride or bromide.
- the process of the present invention also includes the use of corresponding acid anhydride instead of said acid halide.
- the riboflavin ester is recovered by evaporation of the solvent under reduced pressure or by pouring the reaction mixture into inert solvents in which the riboflavin ester is insoluble.
- those having lower alkanoyl moiety can be conveniently prepared by directly reacting riboflavin with the alkanoic anhydride in the presence of concentrated perchloric acid.
- the butyric ester of riboflavin can be obtained in high yield by adding a small amount of 60% perchloric acid into a mixture of riboflavin and butyric anhydride with stirring at room temperature and then pouring the reaction mixture into water.
- the fatty acid esters of riboflavin thus prepared may be recovered and purified by recrystallization from ether, benzene or ethanol.
- the riboflavin esters of this inven tion are substantially tasteless and odorless, and are quite soluble in many conventional solvents, such as ethanol, pyridine, benzene, chloroform, or neutral fats, in each of which riboflavin itself is almost insoluble.
- riboflavin esters of this invention have the following structural formula:
- the compounds of this invention possess vitamin B activity. When administered orally, the compounds are easily hydrolyzed with human digestive juices into riboflavin and corresponding fatty acids, and effect vitamin B activity. It has been found that the compounds are'hydrolyzed with neither saliva nor gastric juices, but with duodenal juice. Among many of the compounds riboflavin tetrabutyrate is most easily hydrolyzed. This can be illustrated by the test described below.
- each of the substrates was suspended in a mixture'of 0.3 ml. of 0.1 M phosphoric acid-buffered solution (pH 8.5) and 0.2 ml. of human duodenal juice at a concentration of 1x10- M.
- the substrate solutions were incu-' bated for 30 minutes at 37 C. and the degradation rate of each of the substrates was assayed by the lumiflavin fluorescence method (Yagi, J. Biochem., vol. 43, page It has also been found that the compounds of the invention show vitamin B activity on dietary scurvy using male albino rats.
- riboflavin tetrabutyrate increases the body weight of rats as much as free riboflavin and it prevents ariboflavinosis remarkably. However, others were found to have little growth-promoting activity.
- the blood level of total riboflavin rises more slowly, and remains at an effective level for a longer period than with free riboflavimj- Furthermore, the administered riboflavin is substantially excreted in urine for a longer period of time than is free riboflavin. For example, when 5 mg. of free riboflavin is administered to a rabbit, weighting about 3 kg., by intramuscular injection, the blood level of total riboflavin reaches a peak within 30 to 60 minutes and a substantial quantity of the given riboflavin is excreted in urine within a few hours.
- the blood level of total riboflavin reaches a peak on more than 12 hours after the injection, and 30 to 40% of the given riboflavin is excreted in urine within 24 hours.
- Example 1 1 g. of riboflavin was suspended in 300 ml. of a 1:1 mixture of pyridine-chloroform. Into this suspension, 15 g. of palmitoyl chloride in 50 ml. of chloroform was dripped at 0 C. with vigorous stirring within about 1 hour. The mixture was stirred for an additional 14- r H, 10.61 N, 4.21..
- reaction mixture was concen trated to dryness under reduced pressure and the residue was treated with mlaof 90% pyridine at 70 C.
- Example' 5 1 of riboflavin was added to 10 inl. of butyric anhy- To the mixture was added 05ml. of 60% aque-' ous solution of perchloric acid at. room temperature with .vigorous stirringi The reaction mixture was V poured into 50 nil. of water. After the orangefyellowr.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP109760 | 1960-01-14 | ||
| JP3723261 | 1961-10-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3189598A true US3189598A (en) | 1965-06-15 |
Family
ID=31948120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US186327A Expired - Lifetime US3189598A (en) | 1960-01-14 | 1962-04-10 | Fatty acid esters of riboflavin |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US3189598A (de) |
| CH (1) | CH414658A (de) |
| DE (1) | DE1179218B (de) |
| GB (1) | GB943078A (de) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4264601A (en) * | 1979-06-12 | 1981-04-28 | The Board Of Regents Of The University Of Oklahoma | Antihypertensive agents and their use in treatment of hypertension |
| US6268120B1 (en) * | 1999-10-19 | 2001-07-31 | Gambro, Inc. | Isoalloxazine derivatives to neutralize biological contaminants |
| US20050112021A1 (en) * | 2000-06-15 | 2005-05-26 | Gambro, Inc. | Reduction of Contaminants In Blood and Blood Products Using Photosensitizers and Peak Wavelengths of Light |
| US20060094547A1 (en) * | 2002-07-16 | 2006-05-04 | Ouishou Xu | Integrated pulley-torsional damper assembly |
| EP1553099A4 (de) * | 2002-08-02 | 2006-06-28 | Inst Radiation Med Amms Pla | Riboflavinderivat und dessen herstellung und verwendungen |
| US7094378B1 (en) | 2000-06-15 | 2006-08-22 | Gambro, Inc. | Method and apparatus for inactivation of biological contaminants using photosensitizers |
| US7220747B2 (en) | 1999-07-20 | 2007-05-22 | Gambro, Inc. | Method for preventing damage to or rejuvenating a cellular blood component using mitochondrial enhancer |
| US9044523B2 (en) | 2000-06-15 | 2015-06-02 | Terumo Bct, Inc. | Reduction of contaminants in blood and blood products using photosensitizers and peak wavelengths of light |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2825729A (en) * | 1955-05-24 | 1958-03-04 | Upjohn Co | Isoalloxazines |
| US2970995A (en) * | 1959-03-20 | 1961-02-07 | Gen Mills Inc | Reductive acylated products of riboflavin |
-
1962
- 1962-04-10 US US186327A patent/US3189598A/en not_active Expired - Lifetime
- 1962-07-13 DE DET22463A patent/DE1179218B/de active Pending
- 1962-08-10 CH CH963462A patent/CH414658A/de unknown
- 1962-09-18 GB GB35449/62A patent/GB943078A/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2825729A (en) * | 1955-05-24 | 1958-03-04 | Upjohn Co | Isoalloxazines |
| US2970995A (en) * | 1959-03-20 | 1961-02-07 | Gen Mills Inc | Reductive acylated products of riboflavin |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4264601A (en) * | 1979-06-12 | 1981-04-28 | The Board Of Regents Of The University Of Oklahoma | Antihypertensive agents and their use in treatment of hypertension |
| US7220747B2 (en) | 1999-07-20 | 2007-05-22 | Gambro, Inc. | Method for preventing damage to or rejuvenating a cellular blood component using mitochondrial enhancer |
| US6268120B1 (en) * | 1999-10-19 | 2001-07-31 | Gambro, Inc. | Isoalloxazine derivatives to neutralize biological contaminants |
| JP2003512340A (ja) * | 1999-10-19 | 2003-04-02 | ガンブロ、 インコーポレイテッド | 生物学的汚染物質を中和するためのイソアロキサゾール誘導体 |
| US6828323B2 (en) * | 1999-10-19 | 2004-12-07 | Gambro, Inc. | Isoalloxazine derivatives to neutralize biological contaminants |
| US20050112021A1 (en) * | 2000-06-15 | 2005-05-26 | Gambro, Inc. | Reduction of Contaminants In Blood and Blood Products Using Photosensitizers and Peak Wavelengths of Light |
| US7094378B1 (en) | 2000-06-15 | 2006-08-22 | Gambro, Inc. | Method and apparatus for inactivation of biological contaminants using photosensitizers |
| US9044523B2 (en) | 2000-06-15 | 2015-06-02 | Terumo Bct, Inc. | Reduction of contaminants in blood and blood products using photosensitizers and peak wavelengths of light |
| US20060094547A1 (en) * | 2002-07-16 | 2006-05-04 | Ouishou Xu | Integrated pulley-torsional damper assembly |
| EP1553099A4 (de) * | 2002-08-02 | 2006-06-28 | Inst Radiation Med Amms Pla | Riboflavinderivat und dessen herstellung und verwendungen |
| US20060293335A1 (en) * | 2002-08-02 | 2006-12-28 | Qishou Xu | Riboflavin derivative and its manufacture and uses |
Also Published As
| Publication number | Publication date |
|---|---|
| DE1179218B (de) | 1964-10-08 |
| CH414658A (de) | 1966-06-15 |
| GB943078A (en) | 1963-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3189598A (en) | Fatty acid esters of riboflavin | |
| JPH0825955B2 (ja) | ジアセチルレインの獲得および製造方法 | |
| US4379093A (en) | Process for preparing high purity ursodeoxycholic acid | |
| DE3342624A1 (de) | Benzaronderivate, verfahren zu ihrer herstellung und diese derivate enthaltende arzneimittel | |
| DE1795022C3 (de) | Lysergsäurederivate | |
| FR2553409A1 (fr) | Nouveaux benzenesulfonyl-lactames, leur procede de preparation et leur application comme substance active de compositions pharmaceutiques | |
| DE3925496C2 (de) | ||
| FR2502622A1 (fr) | Derives d'imidazo (1,2-a) pyrimidines, leur preparation et leur application en therapeutique | |
| JP2948161B2 (ja) | ジアセチルレインからなる関節炎治療剤 | |
| JPS6246554B2 (de) | ||
| US2280040A (en) | Preparation of nicotinic acid amide | |
| DE1910930A1 (de) | Verfahren zur Herstellung von neuen 1,6-Dimethyl-10alpha-ergolinderivaten | |
| EP1230252B1 (de) | Beta-d-thioxylos-derivate, verfahren zur herstellung und verwendung als arzneimittel | |
| EP0001021A2 (de) | Derivate pentacyclischer Alkaloide, Verfahren zu deren Herstellung, Anwendung für die Synthese von Produkten der Eburnamoningruppe und pharmazeutische Zusammensetzungen | |
| US3553236A (en) | Psoralene and isopsoralene, process for their isolation and separation | |
| JPH0368845B2 (de) | ||
| US3453315A (en) | 9-isopropylidenyl-9,10-dihydro-anthracene-10-carboxylic acid esters | |
| US2926167A (en) | Process of esterifying ib-hydroxy | |
| US4162255A (en) | Process for extracting aristolochic acids | |
| CH640502A5 (de) | 3beta-substituierte 18beta-olean-9-en-30-oylsaeurederivate, solche enthaltende arzneimittel und verfahren zur herstellung derselben. | |
| JPS62174060A (ja) | ５−フルオロウラシル誘導体およびこれを含有する医薬製剤 | |
| LU86706A1 (fr) | Nouveaux derives du benzo(4,5)cyclohepta(1,2-b)thiophene,leur preparation et leur utilisation comme medicaments | |
| AT343114B (de) | Verfahren zur herstellung von neuen 5-methylisoxazol-3-carbonsauresalzen | |
| US3798212A (en) | Resolution of benzodiazepine derivatives | |
| JPS632546B2 (de) |