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    • 专利摘要:
    3-Alkylxanthines characterized by the formula …<CHEM>… wherein R<1> is n-propyl, n-butyl, isobutyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, cyclopropyl, cyclobuty, cyclopentyl of cyclohexylmethyl, and R<2> is hydrogen or methyl, provided that R<2> is methyl when R<1> is n-propyl, n-butyl or isobutyl, or a physiologically acceptable salt thereof, for example the compound 3-cyclopetnyl-3, 7-dihydro-1H-purine-2, 6-dione, have activity against chronic obstructive airway disease or cardiac disease. These compounds are produced by several methods, exemplified by the following one: reacting a compound of the formula …<CHEM>… with a compound of the formula… R<2>-X… wherein R<1> and R<2> have the definition given above and X is -COOH, -CONH2 or -OC-O-CO-R2 and, if necessary, submitting the obtained product to dehydration. The starting compounds wherein R<1> is n-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl or cylohexylmethyl are not previously described in teh literature They are prepared by reacting a compound of the formula R<1>NHCONH2 with cyanoacetic acid, cyclising the produced 1-cyanoycetyl-3-R<1>urea with alkali, nitrosing the so produced 1-R<1>-6-aminouracil with HNO2 and reducing the so produced 1-R<1>-5-nitroso-6-aminouracil with H2//PtO2.
    公开号:SU952105A3
    申请号:SU792824353
    申请日:1979-10-11
    公开日:1982-08-15
    发明作者:Гуннар Челлин Пер；Геран Август Перссон Карл
    申请人:Актиеболагет Драко (Фирма)；
    IPC主号:
    专利说明:

    (54) METHOD FOR PRODUCING DERIVATIVES OF XANTHINE OR THEIR SALTS
    The invention relates to organic chemistry, specifically to a method for producing new heterocyclic compounds, in particular to methods for producing xanthine derivatives of the general formula C-I, where n-propyl, n-butyl, n-pentyl 2-methylpropyl, 2-methylbutyl 3-methylbutyl, 2,2-dimethylpropyl, cyclopropyl, cyclobutyl cyclopentyl, cyclohexylmethyl; R is hydrogen, methyl, and if. R means n-propyl, n-butyl, 2-methylpropyl, then R means methyl, or their salts. Xanthine derivatives are of interest as biologically active compounds, in particular, they can show pharmacological activity and be used in the treatment of respiratory pathways and heart disease. Xanthine or 2,6-dioxipurine and its derivatives are known to be found in plants (for example, together with the derivative caffeine and theophylline it is contained in tea); as well as in animals (in the blood, liver). The xanthine derivatives are used, in particular, theophylline and caffeine, for the treatment of chronic diseases of the respiratory tract and heart diseases. These compounds are usually isolated from plants, in particular, caffeine is isolated from tea production wastes, and also synthetically from uric acid by methylation of amino groups tl. The pharmacological action of caffeine and theophylline in a number of cases has a side effect, they cause sudorozh. Known interaction of nitrogen-containing compounds with organic acids and their derivatives, occurring when heated in an organic solvent. Thus, in particular, boiling o-phenylenediamine with carboxylic acids for 0.5 h produces up to 95% 2-alkyl-6en imidazoles 2, the purpose of the invention is to obtain new xanthine derivatives with biologic activity. This goal is achieved by obtaining xanthine derivatives of general formula I by reacting a compound of the general formula T ir-c-uHi where R has the indicated value, is reacted with a compound of the formula R-X. (Ill) where R has the indicated value j x means the groups -COOH, -CONH, followed by dehydration of the resulting product with sodium hydroxide and isolation of the target product in free form or in the form of a syrup. Dehydration can be carried out by heating the reaction mixture in the absence of a solvent, in the presence of a solid, or by simply boiling the reaction mixture in a high-boiling solvent. Example 1. Preparation of 3-cyclopropyl-3, 7-dihydro-1H-purin-2, b-dione. a) Preparation of 6-amino-1-cyclopropyl-2, 4-C1H, 3H-pyrimidinedione. To a solution of 64 g (IG, 75 mol) of cyanoacetic acid in 25 ml of acetic anhydride, 70 g (0.7 mol) of cyclopropyl urea are added. The solution is stirred at 60-70 ° C for 2 hours. After cooling, white crystals are obtained, which are filtered and washed with ethanol. The resulting compound (76.7 g; 66%) is suspended in 200 ml of hot water, after which 55 ml of 5N sodium hydroxide are added in two portions. The reaction mixture is heated to reflux with NIKOM for 20 minutes and neutralize Sugar
    Iq
    one.
    one
    Uv
    G ta
    l
    V
    I HN-
     They are pressurized with 5N hydrochloric acid, then cooled, and white crystals are obtained, which are filtered. 31 g, 7 g, (42%) of the title compound are obtained, the structure of which is confirmed by NMR data. b) Preparation of 6-amino-1-cyclopropyl-5-nitroso-2, 4- (1H, 3N) -pyrimidinedione. 31.7 g (0.19 mol) of 6-amino-1-cyclopropyl-2, 4- (1H, 3N) -pyrimidinedione are suspended in 250 ml of water. 45 ml of 5 N hydrochloric acid and 15 g (0.22 mol) of sodium nitrite dissolved in water are added to the suspension. The reaction mixture is stirred for 2 hours and after cooling, red crystals are obtained, which are filtered and washed with water. 31.9 g (86%) of the title compound are obtained, the structure of which is: T1bdprevenena MP. c) Preparation of 1-cyclopropyl-5,6-diamino-2, 4- (1H, 3N) pyrimidinedione. 15.9 g of 6-amino-1-cyclopropyl-5-nitroso-2, 4 -. (1H, 3N) -pyrimidinedione in 1 l of dimethylformamide is subjected to hydration at room temperature and a pressure of 200 kPa for 4 hours in the presence of platinum oxide (Iv) The catalyst and the resulting crystals are filtered. After washing the crystals with ethanol, 12.9 g (87%) of the title compound are obtained. d) Preparation of 3-cyclopropyl-3, 7-dihydro-1H-purin-2, 6-dione. A solution of 12 g of 1-CYCLOPROPIL-5,6-diamino-2, 4- (1H, 3N) pyrimidinedione in 50 ml of formic acid is heated under reflux for 2 hours. The hot solution is filtered, 30 ml of chloroform are added and then ether is slowly added. After filtration, 40 ml of 2 N sodium hydroxide are added to the resulting crystals and the reaction mixture is heated under reflux for 1 hour, which is neutralized by the addition of 5 N hydrochloric acid. The crystals obtained are filtered. 7 g (60%) of the title compound are obtained, the structure of which is confirmed by NMR (Table 1). The described reactions are presented in the following diagram. Example 2. Getting 3-cyclobutyl-3, 7-dihydro-1n-purine-2, b-dione. a) Preparation of 6-amino-1-cyclobutyl-2, 4- (1H, 3N-pyrimidine dion.) To a solution of 30 g (0.35 mol) of cyanoacetic acid and 100 ml of acetic anhydride, 36.1 g (0.32 ml) are added. mol of cyclobutyl urea. The solution is stirred at 60-70 ° C for 2 hours. After cooling, white crystals are obtained, which are filtered and washed with ethanol. The intermediate compound obtained (36.4 g; 63%) is suspended in 100 ml of hot water. 50 ml of sodium hydroxide are then added in portions, and the reaction mixture is heated under reflux for 20 minutes. e-crystals that are filtered. 3.6 g (20%) of the indicated compound are obtained, the structure of which is confirmed by NMR. b) Preparation of 6-amino-1-: Cyclobutyl-5-nitroso-2, 4- (1H, 3N) - 3-g (0.0166 mol) of 6-amino-1-cyclobutyl-2, 4- (1H, 3N) pyrimidinedione pyrimidinedione is suspended in 25 ml of water. To the suspension are added 4 ml of 5 N hydrochloric acid and 1.3 g (0.019 mol) of sodium nitrite dissolved in water. The reaction mixture is stirred for 3 hours. The resulting red crystals are filtered and washed with water. 3.1 g (89%) of the title compound are obtained, the structures of which are confirmed by NMR. c) Preparation of 1-cyclobutyl-5,6-diamino-2, 4- (1H, 3N) -pyrimidinedione. 6.9 g of 6-amino-1-cyclobutyl-5-nitro ZO-2.4- (1H, 3N) -pyrimidinedione in a medium of 250 ml of dimethylformamide is subjected to hydrogenation at room temperature and a pressure of 200 kPa for 2 hours in the presence of 0, 1 g of platinum oxide. The catalyst and the resulting crystals are filtered. After washing the crystals with ethanol, 3.5 g (54%) of the title compound are obtained. d). Preparation of 3-cyclobutyl-3, 7-1H purin-2, 6-dione. A solution of 3.5 g of 1-cyclobutyl-5,6-diamino-2, 4- (1H, 3N) pyrimidinedione in 20 ml of formic acid is heated under reflux for 2 hours. After filtration of the hot solution, 20 ml of chloroform are added then ether is then slowly and after filtration, 20 ml of 2 N sodium hydroxide are added to the resulting crystals. The reaction mixture is heated with reverse
    H
    R
    VD / C
    / L
    -W
    A refrigerator for 1 h, then neutralized by the addition of 5 N hydrochloric acid. The resulting crystals are filtered and recrystallized from 150 ml of ethanol. 1.4 g (38%) of the title compound are obtained, the structure of which is confirmed by NMR (Table 1). Froze Getting 3-cyclopentyl-3, 7-dihydro-1H - Puri 1-2,6-dione. a) Preparation of 6-amino-1-cyclopentyl-2, 4- (1H, 3N) -pyrimidinedione. 192 g (1.5 mol of cyclopentyl urea) are added to a solution of 136 g (1.6 mol) of cyanoacetic acid and 400 ml of acetic nhydride. The solution is stirred at 60-7 (fc for 2 hours. After cooling, white crystals are obtained which are filtered and washed with ethanol. The intermediate compound thus obtained (192 g; 66%) is suspended in hot water and 195 ml of 5 N sodium hydroxide is added in portions. The reaction mixture is heated under reflux for 20 minutes and then neutralized by the addition of 5 N hydrochloric acid After cooling, 159 g of white cristae allov cyclopentyl urea is filtered, the filtrate is evaporated and the residue is heated under reflux in 200 ml of 1N sodium hydroxide. After cooling, cyclone urea is filtered and the filtrate is neutralized by adding 5 N hydrochloric acid. The resulting crystals are filtered. The structure of which is confirmed by NMR. b) Preparation of 6-amino-1-cyclopentyl-5-nitroso-2, 4- (1H, 3H) -pyrimidinedione. 12.4 g (0.064 mol) of 6-amino-1-cyclopentyl-2, 4- (1H, 3N) -pyrimidinedione is suspended in 200 ml of water, after which 14 ml of 5 N hydrochloric acid and 4.8 g (4 0.07 mole of sodium nitrite dissolved in water. The reaction mixture is stirred for 1 h and washed with water. 12.9 g (90%) of the title compound are obtained, the structure of which is confirmed by NMR. c) Preparation of 1-cyclopentyl-5,6-diamino-2, 4- (1H, 3N) -pyrimidinedione. 12.9 g of 6-amino-1-cyclopentyl-5-nitroso-2, 4- (1H, 3N) -pyrimidinedione in an environment of 30 ml of 2 N hydrochloric acid is subjected to hydrogenation at room temperature and a pressure of 200 kPa for 3 hours in the presence of 0.1 g of platinum oxide. The catalyst is filtered and the filtrate is neutralized by the addition of 5 N sodium hydroxide. The resulting crystals are filtered. 6D g (50%) of the title compound are obtained. d) Preparation of 3-cyclopentyl-3, 7-dihydro-1H-purin-2, b-dione. A solution of 6.1 g of 1-cyclopentyl-5,6-diamino-2, 4- (IH, 3N) pyrimidinedione in 25 ml of formic acid is heated under reflux for 1 hour. After filtering off a hot solution, 20 ml of chloroform are added and then slowly a simple ether. The resulting crystals are filtered. The intermediate compound thus obtained is heated under reflux for 30 hours in 30 ml of 2 N sodium hydroxide and then neutralized by the addition of 5 N hydrochloric acid. 3.4 g of C53% of the title compound is obtained, the structure of which is confirmed by NMR (Table 1). Other compounds of general formula II are prepared according to analogous schemes of Examples 1-3. Example 4. Obtaining 3,7-dihydro-3-cyclohexylmethyl-1H-purin-2, 6-dione. 2 g of 5, b-diamino-1-cyclohexylmethyl-2, 4- (1H, 3N) -pyrimidinedione in a medium of 10 ml of formic acid is heated under reflux for 1 hour. After adding 5 ml of chloroform, ether is slowly added. The resulting crystals are filtered and the intermediate compound (2.1 g) is heated under reflux in 15 ml of 2 N sodium hydroxide for 1 hour, after which the mixture is neutralized by the addition of 5 N hydrochloric acid. 1.7 g of the title compound are obtained, the structure of which is confirmed by NMR (Table 1). Example 5. Obtaining 3,7-dihydro-3- (2,2-dimethylpropyl) -1H-purine -2fb-dione, 4.0 g of 5,6-diamino-1- (2,2-dimethylpropyl) -2, 4- (1H, 3N) -pyrimidinedione. In 20 ml of formamide is heated under reflux for 30 minutes. After cooling, 30 ml of this NOL is added. The resulting yellow crystals are filtered and recrystallized from 15 ml of dimethylformamide. 2.0 g of the title compound are obtained, the structure of which is confirmed by NMR (Table 1 Example 6. Preparation of 3,7-dihydro-8-methyl-3-cyclohexylmethyl-1H-purine-2, b-dione. 1 g5, b- diamino-l-cyclohexylmethyl-2,4- (lH, 3N) pyrimidinedione in a mixture of 5 ml of acetic acid is heated under reflux for 1 hour, then 2 ml of chloroform and ether are added slowly. The resulting crystals are filtered. the intermediate compound in the medium of 10 ml of 2 N sodium hydroxide is heated under reflux for 1 h and then neutralized by the addition of 5 N x hydrochloric acid. The crystals are filtered and recrystallized from 80 ml of ethanol to give 0.6 g of the indicated compound, the structure of which is confirmed by NMR (Table 1). Example 7. Preparation of 3-cyclopentyl-3, 7-dihydro-8-methyl-1H- purin-2, 6-dione. 1,6 1-cyclopentyl-5,6-diamino-2,4- (1H, ZN) -pyrimidinedione in a medium of 10 ml of acetic acid is heated under reflux for 15 minutes. After-addition 10 ml of chloroform are slowly added to the ether. The resulting crystals are filtered, and the intermediate compound is heated in 5 ml of 2 N sodium hydroxide reflux for 1 h and then neutralized by adding 5 N hydrochloric acid and then filtered again and kri.stally perekrista; llizovyvayut from 25 ml of 80% ethanol. 0.7 g of the title compound is obtained, the structure of which is confirmed by NMR (Table 1). Example 8. Obtaining 3,7-dihydro-3- (2,2-dimethylpropyl) -8-methyl-1H-purine-2, 6-dione. 10.4 g of 5,6-diamino-1- (2,2-dimethylpropyl) -2, 4- (1H, 3N) -pyrimidinedione in a medium of 75 ml of acetic acid is heated under reflux for 1 h, then 50 m of chloroform and slowly simple ether. The resulting crystals are filtered, then heated under reflux in 50 ml of 1 N sodium hydroxide for 1 hour and then neutralized by the addition of 5 N hydrochloric acid. 7.2 g of the title compound are obtained, the structure of which is confirmed by NMR (Table 1). Pr and m-e p 9. Preparation of 3,7-dihydro-8-methyl-3- (2-.methylpropyl) -1H-purin-2, b-dione. 10 g-5, b diamino-1- (2-methylpropyl) -2,4- (1H, 3N) pyrimidinedione in 50 ml of acetic acid is heated under reflux for 1 h, then 30 ml of chloroform are added and ether. The resulting crystals are filtered and this intermediate is heated under reflux in 30 ml of 2 N sodium hydroxide for 1 h, after which it is neutralized with 5 N hydrochloric acid, the crystals are filtered and recrystallized from 50 ml of acetic acid. 3.3 I. 1 of the title compound is obtained. The structure of which is confirmed by NMR (Table 1), Example 10. Preparation of 3-cyclopropyl-3, 7-dihydro-8-methyl-1-purine-2, 6-dione. A solution of 6.4 g of 1-cyclopropyl-5,6-diamino-2, 4- (1H, 3N) -pyrimidinedione in 20 ml of acetic acid is heated under reflux for 2 hours, then the solution is evaporated and the residue is heated under reflux for 1 h in medium 40 ml of 2 N sodium hydroxide and 80 ml of 5 N sodium hydroxide, then neutralized with 5 N hydrochloric acid. After filtration, 1.85 g (26%) of the indicated target product is obtained, the structure of which is confirmed by NMR (Table 1). Example 11. Getting 3-cycle butyl-3,7-dihydro-8-methyl-1H-purin-2, 6-dione. A solution of 2.2 g of 1-cyclobutyl-5, b-diabno-2, 4- (1H, ZN) -pyrimidinedione in 10 ml of acetic acid is heated under reflux for 2 h, then the solution is evaporated and the resulting residue is heated under reflux fridge in medium 30 ml of 5 N sodium hydroxide for 1 h, then neutralized with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 100 ml of ethanol. This gives 0.4 g (18%) of the desired product, the structure of which is confirmed by NMR (Table 1). Example 12. Preparation of 3,7-dihydro-3-pentyl-1H-purin-2, b-dione 37.4 g 5 , b-diamino-1-pentyl-2,4- (1H, 3N) -pyrimidinedione in 50 ml of formic acid is heated under reflux for 2 hours. Then 50 ml of chloroform and 10 ml of ether are successively added and the crystals are filtered. 36.8 g of the amide derivative are heated with a reverse fridge in 50 ml of 5 N sodium hydroxide for. 2 chi neutralized with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 1.8 l of ethanol. Get 18.3 g of the specified target product, the structure of which is confirmed by NMR (table. 1). Example 13. Preparation of 3,7-digiro-8-methyl-3-pentyl-1H-purin-2, 6-dione. A solution of 5 g of 5,6-diamino-1-pentyl-2, 4- (1H, 3N) -pyrimidinedione in 15 ml of acetic acid is heated under reflux for 2 hours. The hot solution is filtered and 15 ml are subsequently added. chloroform and 5 ml of ether; crystals of 5.5 g of the amide derivative are filtered and heated under reflux in 25 ml of 2 N sodium hydroxide for 2 hours and neutralized with 5 N hydrochloric acid. Crista 1L is filtered and recrystallized from 225 ml of ethanol. Obtain 2.1 g (37%) of the specified target product, the structure of which is confirmed -. on NMR (table. 1). Example 14. Obtaining 3,7-. -dihydro-3- (2-methyl-1-butyl) -1H-purine-2, 6-dione. 17.3 g of 5,6-diamino-l- (2-methyl-l-butyl) -2,4- (1H, 3N) -pyrimidinedione is heated in 30 ml of formic acid for 2 hours. Then 20 ml are added successively. chloroform and 5 ml of amide ether. the derivative (17.0 g) is heated under reflux in a medium of 50 ml of 2 N sodium hydroxide for 2 hours and. neutralized with 5 N hydrochloric acid. The crystals are filtered and percrystallized from 400 ml of ethanol. Obtain 10 g of the specified target product, the structure of which is confirmed by NMR (table. 1) .. Example 15. Obtaining 3,7-dihydro-8-methyl-3- (2-methyl-1-butyl) -1H-purine-2, 6 -dione. A solution of 3.2 g, 6-diamino-1- (2-methyl-1-butyl) -2,4- (1H, 3N) pyrimidinedione in 8 ml of acetic acid is heated under reflux for 2 hours. Hot solution filtered and then 8 ml of chloroform and 4 ml of ether are sequentially added. The crystalline amide derivative remaining after filtration is heated under reflux in a medium of 10 ml of 2 N sodium hydroxide for 2 hours and then neutralized with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 75 ml of ethanol. Obtain 2.0 g of the specified target product, the structure of which is confirmed by NMR (table. 1). Example 16. Obtaining 3,7-dihydro-3- (3-methyl-1-butyl) -1H-purin-2, 6-dione. A solution of 21 g of 5,6-diamino-1- (3-methyl-1-butyl) -1H-purine-2,6-dione in 50 ml of formic acid is heated under reflux for 2 hours. The hot solution is filtered, after 50 ml of chloroform and 20 ml of ether were successively added. The crystalline amide derivative (20.2 g) that remains after filtration is heated under reflux in 25 ml of 5 N sodium hydroxide for 2 hours and then neutralized with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 500 ml of ethanol. Obtain 9.7 g (44%) of the specified target product, the structure of which is confirmed by NMR (table. 1).
    Example 17. The preparation of 3,7-dihydro-8-methyl-3- (3-methyl-1-butyl) -1H-purin-2, 6-dione.
    A solution of 3.5 g of diamino-1- (3-methyl-1-butyl) -2 4- (IH, 3N) -pyrimidinedione in 25 ml of acetic acid is heated under reflux for 2 hours. The hot solution is filtered and then 20 ml of chloroform and 10 ml of ether are added. After filtration, the crystalline amide derivative (5.2 g) is heated under reflux in 25 ml of 2 N sodium hydroxide for 2 hours and then neutralized with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 30 ml of ethanol. Obtain 1.9 g (34%) of the specified target product, the structure of which is confirmed by NMR (table. 1).
    Solution 22, b g 5, b-diamino-1-pro-, pil-2,4- (1H / 3N) -pyrimidinedione is heated under reflux in 50 ml of acetic acid for 2 hours, after. which add 30. ml of ethanol and obra4H 2,36t 1H 5,42 p
    t
    2H 3,43r
    1H 5,53r 8H 2,17t
    2H 4.14d
    1.6 Zga
    IH 2H 9H 2H 4.16s 1.23s 4.10d 1.60m
    1H
    5.50p
    1H 8H 2,20m
    4.08s
    2H 9H 1.23s
    4.05d
    2H
    2.50h
    1H bN l, 10d
    The crystals that appear are filtered, heated under reflux in 80 ml of 2N sodium hydroxide for 2 hours, followed by neutralization with 5N hydrochloric acid. The crystals are filtered and. recrystallized from 2.1 l of ethanol. Obtain 9.8 g (38%) of the specified target product, the structure of which is confirmed by NMR (table. 1).
    Example 19. Obtaining 3,7-dihydro-3-butyl-8-methyl-1H-purin-2, 6-dione.
    A solution of 7.6 g of 1-butyl-5, b-diamino-2, 4- (lH, 3N) pyrimidinedione in 20 ml of acetic acid is heated under reflux for 2 hours. The solution is evaporated and the residue is heated under reflux in a medium of 40 ml of 2 N sodium hydroxide for 2 hours, followed by neutralization with 5 N hydrochloric acid. The crystals are filtered and recrystallized from 350 ml of ethanol. Obtain .1.8 g (21%) of the specified target product, the structure of which is confirmed by NMR (table. 1).
    Table
    1H 8.40 s ll, 43b 13.83b
    2H 2H 1.95m GEL l, 13t
    2H 4.221
    4Н1.77m ЗН 1.08t
    2H 4.23t 2H 1.93r 4H 1.57t ZN- l, 12t
    2H 4.20t 6H 1.70t GH l, 13t
    2H 4.13d 1H 2.27t 2H 1.50t 6H 1.10t
    2H4,07d
    1H2.33t
    2N1,50t
    bN1,13t
    2H 4.30 t 2H 1.83m IH 1.83m
    2H 4.25t 2H 1.87m 6H 1.20m
    2H 4,05t 2H 1,98m 3 Hi, lot
    IH 5.53p
    2H 3.40m 4H 2.37n
    Note. Data
    In tabl; 2 shows the data on the headlights-60 macro-activity of xanthine derivatives of general formula I, The second column of the table shows the data on the ratio of activity, bronchodilation, theophylline to the proposed 65
    Continued table. l
    SN 2.67 s 11.27 b 13.43 b
    ЗН 2,67 s 11,28 s 13,43b
    IH 8.37s ll, 43b 13.67b
    3H 2.67 s 11.23 s 13.70 b
    IH 8.40 s ll, 37b 13,52b
    3H 2.67 s 11.30 s 13.47b
    1H 8.33 ll, 37b 13.60
    SS 2.70 s ll, 27b 13.40 b
    OA 2.67 s ll, 02b 13,37b
    3H 2.67 s ll, 28b 13.47b
    NMR are given in J ppm. Dostomedimethylsulfoxide - d (, (cf- 2.83).
    ritor
    xanthine derivative. The third column shows the symptoms detected before killing JvibnueA, which were given intravenous compounds at the same injection rate. Tonic convulsions (ton.sud.) Were found in all animals after giving theophylline and caffeine. The proposed compounds, the activity of which was studied in 10 animals, did not cause tonic convulsions. In some animals, the compounds of Examples 1 g, 2 g, and 9 caused convulsions of a clonic type or a mixed clonic-tonic type, the intensity of which is much lower than the intensity of convulsions caused by theophylline and caffeine. The fifth column indicates cardiotonic activity as positive chronotopic activity.
    权利要求:
    Claims (3)
    [1]
    Claim
    A method of producing xanthine derivatives of the general formula I. eus-schh 0 M where R ^ has the indicated meaning, is reacted with a compound of the formula III
    R 1 - X h where R 1 is n-propyl, n-butyl, n-pentyl,
    [2]
    2-methylpropyl, 2-methylbutyl,
    [3]
    3-methylbutyl, 2,2-dimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexylmethyl;
    R 1 is hydrogen or methyl, and if R ' 1 means n-propyl, n-butyl, 2-methylpropyl, then R a starts methyl, or their salts, if so with I am that the compound of general formula II · where has the indicated meaning;
    X means —COOH, —CONHij groups, followed by dehydration of the obtained 5Q product with sodium hydroxide and isolation of the target product in free form or in the form of a salt.
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    AU530717B2|1983-07-28|
    IE49184B1|1985-08-21|
    AT1145T|1982-06-15|
    NO793377L|1980-04-22|
    SE7810947L|1980-04-21|
    AU5187179A|1980-05-01|
    PL219065A1|1980-06-16|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE7810947A|SE7810947L|1978-10-20|1978-10-20|3-ALKYLXANTHINES|
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