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    1419994 Heterocyclicalkylaminoheterocyclic compounds SMITH KLINE & FRENCH LABORATORIES Ltd 30 April 1974 [3 May 1973 26 July 1973] 21063/73 and 35551/73 Heading C2C Novel compounds of the Formula I wherein A is a chain of 3 or 4 atoms which chain comprises at least one carbon atom and may also comprise a sulphur atom, a nitrogen atom, two nitrogen atoms or a nitrogen and a sulphur atom said chain also comprising a keto, thione or, where possible, a sulphone grouping and may be substituted by one or two C 1-4 alkyl, aryl or aralkyl groups or in such a way that the resultant structure forms with the adjacent ring carbon and nitrogen atoms shown a bicyclic system, one ring of which is a phenyl ring; R is a grouping Het-CH 2 Z(CH 2 ) n where Het is an imidazole, pyridine, thiazole, isothiazole, thiadiazole, which ring is optionally substituted by C 1-4 alkyl, amino, hydroxy or halogen; Z is sulphur or methylene and n is 2 or 3 and salts thereof may be prepared by reacting a compound of the Formula VII or VIII where B is the same scope as A except the keto, thione or sulphone is protected, and Q is halogen methanesulphonyl, thiol or alkylthio with an amino compound R<SP>1</SP>NH 2 wherein R<SP>1</SP> either has the same significance as R or is a group such that the product of the said reaction may be converted to a compound of the invention and where necessary removing any protective group from the protected keto, thione or sulphone grouping and when R<SP>1</SP> is not the same as R, converting R<SP>1</SP> to R. Various substituted 2-methylthio-2-imidazolin- 4-ones isolated as their hydroidides were prepared by reacting the corresponding 2-mercapto- 2-imidazolin-4-ones with methyl iodide. 5 - Benzyl - 6 - methyl - 2 - methylthio - 4 - pyrimidone may be prepared by reacting 5- benzyl-6- methylthiouracil in base with methyl iodide. Pharmaceutical compositions of the compounds I with the usual excipients are antagonistic to certain actions of histamine when administered orally, parenterally or topically.
    公开号:SU719500A3
    申请号:SU742021439
    申请日:1974-04-30
    公开日:1980-02-29
    发明作者:Джон Дюрант Грэхэм；Колин Имметт Джон；Робин Ганеллин Чарон
    申请人:Смит Клайн Энд Френч Лабораториз Лимитед (Фирма)；
    IPC主号:
    专利说明:

    a theme whose cycle is a phenyl core; , Q is a halogen, methanesulfonyl, thiol, or alkane that is reacted with an amino derivative of the general formula NH2R, where R has the above values. Most preferably, the compounds of the formulas III and IV are prepared TiX X pg 1 1 H In which R has the above-mentioned meanings; X is oxygen or sulfur; YI and Y2 are the same or different hydrogen, lower alkyl, aryl or aralkyl, or YI and Y2 together with adjacent carbon atoms form phenyl; YS and Y4 are the same HjiH different, hydrogen, lower alkyl, aryl or aralkyl, and where Het is imidazole or methylimidazole; n is 2. Example 1. Dihydrochloride (4-methyl-5-imidazolylmethylthio) -ethylamio-pyrim-idon-4. A mixture of 2.6 g of 4 (5) - (2-aminoethyl) -thiomethyl5. (4) -methylimidazole and 1.4 g of 2-methylthiopyrimidopa-4 is heated for 30 minutes at 150 ° C, then 2 hours at 150-160 ° C . After cooling, the reaction mixture was triturated with water, the resulting base was filtered and dissolved in 5N hydrochloric acid. It is evaporated to dryness, the residue is crystallized from aqueous ethanol, and 2.1 g of dihydrochloride (4-methyl-5-imidazolylmethylthio) -ethylamino-nerimidone, 4, are obtained; m.p. 246-248 ° C. Calculated,%: C 39.1; H 5.1; N 20.7; S 9,5; C1 20.95. CiiHirCbNsOS. Found,%: C 39.25; H 5.2; N 20.4; S 9.6; C1 20.5. By recrystallization of the initially obtained base from aqueous alcohol, a pure base is obtained; m.p. 219-22 PCs. Example 2. Dihydrochloride (methyl - 5 - imidazolylmethylthio) -ethylamino-6methylpyrimidone-4. By the above method, from 4.5 g of 4 (5) (2-aminoethyl) -thiomethyl-5- (4) -meth limidazole and 2.7 g of 6-methyl-2-methylthiopyrimidone-4 receive the dihydrochloride (4-methyl-5-imidazolylthio) l ethylamino-6-methylpyrimidone-4; m.p. 247-250 ° C (from ethanol). Calculated,%: C 40.9; H 5.4; N 19.9; S 9.1; C1 20.1. Ci2Hi9Cl2N5OS. Found,%: C 41.1; H 5.7; N 19.8; S 8.9; C1 19.8. Example 3. Dihydrochloride (4-methyl-5-imidazolylmethylthio) -ethylamino -5,6 dimethylpyrimido 1a-4. As described in Example 1, a method of 4.1 g of (5) - (2-aminoethyl) - thiomethyl-5 (4) -methyl; lmidazole and 2.6 g of 5,6-dimethyl-2-methylthiopyrimndone-4 is obtained by dihydrochloride (4 -5- imidazolnmetiltio) - ethylamino 5, 6-dimethylpyrimidone-4; m.p. 235-237 ° C (from ethanol). Calculated,%: C 42.6; H 5.8; N19.1; S 8.75; C1 19.4. CisHgiClzNsOS. Found,%: C 42.8; H 6.0; N 18.7; S 8,6; C1 18.8. Example 4. The dihydrochloride (4-imidazolyl) -butylamino-pyrimidone-4. The method described in Example 1 out of 2.1 g of 4 (5) - (4-aminobutyl) -imidazole and 1.4 g of 2-methylthiopyrimidone-4 gives 2-4- (4-imidazolyl) -butylamino-pyrimidone-4 dihydrochloride; m.p. 215-222 ° C (from ethanol). Calculated,%: C 43.15; H 5.6; N22.9; C1 23.2. CnHnCUNsOS. Found,%: C 43.15; H 5.6; N 22.5; C1 22.8. Example 5. The dihydrochloride (4-methyl-5-imidazolylmethylthio) -ethylamino-thiopyrimidone-2. A solution of 7.4 g of 4 (5) - (2-aminoethylthiomethyl) -5 (4) -methylimidazole and 4.1 g of 2,4-dimercaptopyrimidine in 150 ml of water is boiled for 12 hours. After cooling, the precipitated oil is decanted, washed with water (3 x 50 ml) and dissolved in 2n. hydrochloric acid. The solution is evaporated to dryness and the residue is recrystallized from ethanol to give (4-methyl-5-imidazolylmethylthio) -ethylamino-thiopyrimidone-2 Dihydrochloride; m.p. 254-257 ° C. Calculated,%: C 37.3; H 4.8; N 19.8; S 18.1. CiiHijClaNsSs. Found,%: C 37.2; H 4.9; iN 19.7; S 18.0. Example 6 (4-methyl-5-imidazolylmethylthio) -ethylamino-2-imidazolinone dihydrochloride-4. A solution of 3.4 g of 4 (5) - (2-aminoethylthiomethyl) -5 (4) -methyl imidazole and 2.6 g of 2-methylthio-2-imidazolinone-4 in 20 ml of absolute ethanol is left for 4 days at room temperature. The mixture is filtered, dissolved in dilute hydrochloric acid, the solution is alkalinized with an aqueous solution of potash, and (4-methyl-5-imidazolylmethylthio) -ethylamino-2-imidazolinone-4 is obtained; m.p. 224-225 ° C (decomposition). Dihydrochloride with t. Pl. 226-228 ° C (decomposition) is obtained by dissolving the base in dilute hydrochloric acid, followed by evaporation to dryness and recrystallization of the residue from aqueous ethanol.
    Calculated,%: C 36.8; H 5.25; N 21.5; S 9,8; C1 21.7.
    CioHnCbNsOS.
    Found,%: C 31.1; H 5.4; N 21.45; S 9.7; C1 21.6.
    Example 7. (4-Methyl-5-imidazolylmethylthio) -ethylamino -4- (1H) -quinazolinone.
    By heating a mixture of 2.6 g of 4 (5) - (2-aminoethyl) -thiomethyl-5 (4) -methylimidazole with 1.9 g of 2-methylthio-4 (1H) -quinazolinone at 120 ° C for 4.5 h, 2.7 g of crude base are obtained, which is acidified with hydrochloric acid as described in example 1, and after recrystallization from ethanol-ether, (4-methyl-5-imidazolylmethylthio) -ethylamino -4 (1H) -quinazolinone dihydrochloride is obtained; m.p. 249-252 ° C.
    Calculated,%: C 46.4; H 4.9; N18.0; S 8.3.
    CisHuCbNsOS.
    Found,%; C 45.8; H 4.9; N 17.8; S 8.1.
    Example 8. (4-Methyl-5-imidazolylmethylthio) -ethylamino-6-n-propyl pyrimidone-4.
    5 g 4 (5) - (2-amine oethyl) -thiomethyl-5 (4) methylimidazole and 5 g 6 n. propyl-2-methylthiopyrimidone-4 by the method described in example 1, a hygroscopic (4-methyl-5-imidazolylmethylthio) -ethyl-amino-6-n-propylpyrimidone-4 dihydrochloride is obtained; m.p. 125-130 ° C.
    Calculated 44.2; H 6.1; N 18.4; S 8.4; C1 18.6.
    CnHssCliNsOS.
    Found,%: C 44.3; H 6.2; N 18.3; S 8,2; C1 18.7.
    Example 9. 2- 2- (4-methyl-5-imidazolylmethylthio) -ethylamino-5-ethyl-6-methylpyrimidone-4 dihydrochloride.
    From 2 g of 4 (5) - (2-aminoethyl) -thiomethyl-5 (4) methylimidazole and 1.46 g of 5-ethyl-6-methyl-2-methylthiopyrimidone-4 using the method described in example 1, 2-, 2- ( 4-methyl-5-imidazolylmethylthio) -ethylamino -5-ethyl-6-methylpyrimidone-4; m.p. 203-207 ° C (izobutanol).
    Calculated,%: C 44.2; H 6.1; N 18.5; S 8.4; C1 18.6.
    SNNGSYNYABS.
    Found,%: C 43.6; H 6.1; N 17.9; S 8.0; C1 18.5.
    Example 10. (4 - methyl-5-imidazolylmethylthio) - ethylamino-5-methyl-2-imidazolikon-4.
    A solution of 15 g of 5-methyl-2-thiogidantoin and 16.3 g of methyl iodide in 130 ml of absolute ethanol is boiled for 1.5 hours and left at 0 ° G until the next day. The precipitated crystals are filtered, washed with ether, to obtain 17.8 g of 2-methylthio-5-methyl-2-imidazolinone-4 hydroiodide; m.p. 170-173 ° C.
    A solution of 2.7 g of the hydroiodide prepared above, 2.5 g of 4 (5) - (2-amino-ethyl) -thiomethyl 5 (4) -methyl imidazole and 1 g of triethylamine in 20 ml of absolute ethanol are kept for 10 days at room temperature. The precipitated crude product 1.6 g with m. PL. 218 ° C is dissolved in hydrochloric acid and the solution is prepared, acidified with a saturated aqueous solution of potash, and {4-methyl-5-imidazolylmethylthio) -ethylamino-5-methylimidazolinone-4 hydrate is obtained; m.p.
    216-220 ° G.
    Calculated,%: C 48.3; H 6.5; N 25.6; S 11.7.
    CnH, 7N5OS-l / 3H20. Found,%: C 48.5; H 6.4; N 25.4; S 11.9.
    Example I. 5,5-Dimethyl-2- 2- (4-methyl 5 - imidazolylmethylthio) -ethylamino -2-imidazolinone-4.
    The method described in Example 10 converts 14.4 g of 5,5-dimethyl-2-thiohydantoin into
    17.4 g of 2-methylthio-5,5-dimethyl-2-imidazolinone-4 hydroiodide; m.p. 187-189 ° C. A solution of 5.7 g of hydroiodide and 6.85 g of 4 (5) - {2-aminoethyl) -thiomethyl - 5 (4) - methylimidazole in 45 ml of absolute ethanol is kept
    4 days at room temperature. The reaction mixture is evaporated to dryness, the residue is recrystallized from water and 3.1 g of 5,5-dimethyl-2- 2- (4-methyl-5-imidazolylmethylthio) -ethylamino-2-imidazolinone-4 are obtained; m.p. 232-236 ° C. Upon further recrystallization, an analytically pure sample is obtained; m.p. 235-237 ° C.
    Calculated,%: C 51.2; H 6.8; N 24.9; S 11 4
    CisHisNsOS.
    Found,%: C 50.9; H 6.9; N 24.8; S 11.4. Example 12. 5-Benzyl-2- 2- (4-methyl-5-imidazolylmethylthio) -ethylamino -2-imidazolinone-4.
    The method described in Example 10 was used to convert 5-benzyl-2-thio-hydantoin to 2-methylthio-5-benzyl-2-imidazolinone-4 hydroiodide; m.p. 192 194C.
    A solution of 2.5 g of hydroiodide, 1.9 g of 4 (5) - (2-amino-ethyl) -thiomethyl-5 (4) -methyl-imidazole and 0.74 g of triethylamine in 15 ml of absolute ethanol is kept for 4 days at room temperature. The reaction mixture is evaporated to dryness, the residue is dissolved in 25 ml of isopropanol, the resulting solution is poured into 200 ml of ether, to obtain 5-benzyl-2 2- (4-methyl-5-imidazolylmethylthio) -ethylamino-2-imidazolinone-4 (1.23 d); m.p. 104-107 ° C.
    Example 13. (4-Methyl-5-imidazolylmethylthio) -ethylamino - (1H) - pyridone-6.
    A mixture of 2 g of 4 (5) - (2-aminoethyl) -thiomethy.L5 (4) -methylimidazole and 11.9 g of 2-bromo-6-ethoxypyridine is heated while moving.
    4 h at 160 ° C. After cooling, the reaction mixture is a solution. in 20% war Hydrobromic acid and the solution is extracted with ether to recover unreacted 2-bromo-6-ethoxypyridine.
    The aqueous layer is carbonated.
    potassium, extracted with chloroform and the combined extract is washed with water and dried over magnesium sulfate. After distilling off the chloroform, the residue is chromatographed on silica gel, elgated first with ethyl acetate to remove impurities, then with an ethyl acetate-methanol-chloroform system in a 4: 1: 2 ratio to elute the desired product. Packing the eluate gives 2-ethoxy-6- 2- (4-methyl-5-imidazolylmethylthio) ethylamino-pyridine in the form of an oil, which when treated with a solution of picric acid in ethanol forms a dipicrate with m.p. 172 ° C
    A solution of ethoxypyridine (3.4 g based) in 100 ml 5 and. hydrochloric acid is heated for 2.5 hours at boiling point. The reaction mixture is then evaporated to dryness, the residue is dissolved in a minimal amount of water, the solution is hemmed, acidified with an aqueous solution of potash, washed with chloroform, left to morning at 0 ° C. The precipitated crystals of (4-methyl-5-imidazolylmethylthio) -ethylamino- (1H) -pyridone-6 are collected and recrystallized from water to give a pure product with m.p. 85 ° C.
    Calculated,%: C 54.5; H 6.1; N 21.2; S 12.1.
    Ci2Hi6N40S.
    Found,%: C 54.25; H 6.0; N 20.9; S 11.9.
    Example 14. (4-Methyl-5-imidazolylmethylthio) -ethylamino - (1H) -niridone-4.
    A mixture of 4.6 g of 4 (5) - (2-aminoethylthio) -methyl5 (4) -methylimidazole and 3.8 g of 2-bromopyridone-4 is heated for 3 hours at 160 ° C with stirring. After cooling, the reaction mixture is chromatographed on silica gel, eluting first with a system of ethyl acetate-isopropanol (5: 1) to remove unreacted 2-bromiridone-4 and then isopropanol-ethanol (5: 1) to isolate the product. After evaporation of the combined eluates, the residue is purified, followed by ion exchange chromatography using an IPA 400 resin (in OH-form) and eluting first with water to remove unreacted amine, then 1N hydrochloric acid to recover the product. After the acidic fractions are quenched and the residue is recrystallized from isopropanol ethyl acetate, (4-methyl-5-imidazolylmethylthio) -ethylamino- (1H) -pyridone-4 is obtained; m.p. 208-210 ° C.
    , Example 15. (4-Methyl-5-imidazolylmethylthio) - ethylamino -1,2,4-benzothiadiazin-1, 1-dioxide.
    A mixture of 5.58 g of 3-methylmercapto-1,2,4-benzothiadiazin-1, 1-dioxide and 4.20 g of 4-methyl-5 (2-aminoethylthio) -methylimidazole is heated for 2 hours at 140-150 ° C and then cool. It is dissolved in ethanol, cooled, 5.67 g of solid are obtained, it is recrystallized from water and then from methanol. 4.30 g of (4-methyl-5-imndazolylmethylthio) - ethylamino -1,2,4-benzothiadisin1, 1-dioxide are obtained; m.p. 194.5-196 ° C.
    Calculated,%: C, 47.8; H 4.9; N 19.9; S 18.3.
    C 4H 7 N5O2S2 Found,;%: C 48.0; P 5.0; N 19.8; S 18.2.
    Example 16. (4-Methyl-5-imidazolylmethylthio) -ethyl-5,6-dihydro-1,2,4-thiadiazin-1, 1-dioxide.
    A mixture of 4 g of 4-methyl-5- (2-aminoethylthio) -methylimidazole and 4.2 g of 3-methylthio-5,6-dihydro-1, 2,4-thiadiazine-1,1-dioxide is heated on an oil bath 4 h at 140 ° C. The product is chromatographed on a silica gel column using ethyl acetate-ethanol (3: 2) as eluant and then recrystallized from ethanol-ether to give 2.2 g of 3-2- (4-methyl-5-imidazolylmethyl) ethyl 5, 6 hydroxy-1,2,4-thiadiazine-1,1-dioxide; m.p. 146-147 ° C.
    Calculated,%: C 39.6; H 5.7; N 23.1.
    CioHi7N5O2S2.
    Paideno,%: C 39.6; H 6.0; N 22.9.
    Example 17. (4-Methl-5-imidazolylmethylthio) -ethylamino-thiazolino-2.
    A solution of 1.71 g of 4-methyl-5- (2-aminoethyl) thiomethylimidazole and 1.33 g of thiazlidine-2-othion-4 in 30 ml of methanol is heated for 1 hour at boiling point. It is evaporated, then recrystallized sequentially from methanol, ethanol and aqueous ethanol, to obtain 1 g (4-methyl-5-imidazolylmethyl-thio) -ethylamino-thiazolinone -2; m.p. igg197 ° C
    Calculated,%: C 44.4; P 5.2; N 20.7; S 23.7.
    C, oHi4N4OS2.
    Found,%: C 44.2; H 5.1; N 20.5; S 23.6.
    Example 18. 3- 2- (4-Methyl-5-imidazolylmethylthio) -ethylamino-6-methyl-1,2,4-triazin-2H-one-5.
    A mixture of 7.64 g of 3-methylthio-6-methyL-1,2,4-triazine and 8.75 g of 5- (2-aminoethylthio) -methyl-4-methylimidazole is slowly heated to 160 ° C and maintained for 1 hour at the indicated temperature. Cool, solid matter dissolved in 100 ml of 2N. hydrochloric acid is filtered, the filtrate is alkalinized with an aqueous solution of potash. The precipitate is collected, washed with water, dried and extracted in Soxhlet with methanol for 16 hours. While cooling the methanol solution, yellowish crystals precipitate. Recrystallized from dimethyl sulfoxide to obtain 7.8 g of (4-methyl-5-imidazolylmethylthio) -ethylamino-6-methyl-1,2,4-triazin-2H-one-5; m.p. 264-266 ° C (decomposition).
    Calculated,%: C 47.1; H 5.7; N 30.0; S 11.44.
    CuH.eNeOS.
    Found,%: C 46.8; H 5.7; N 29.9; S 12,0.
    Example 19. (4-Methyl-5-imidazolylmethylthio) -ethylamino -1,2,4-triazin-2Hon-5.
    A mixture of 8.6 g of 5- (2-amino-ethyl) -thiomethyl-4-methyl-imidazole and 6.68 g of 3-methylthiothriazine-2H-one-5 is slowly heated to 120 ° C and kept at this temperature for 1 hour. After cooling, the solid is recrystallized twice from n-propanol and twice from water, to obtain (4-methyl 5 - imidazolylmethylthio) - ethylamino -1,2,4 triazin-2H-one-5; m.p. 238-238.5 ° C.
    Calculated,%: C 45.1; H 5.3; N 31.6; S 12,0.
    SUNNYBOS.
    Found,%: C 45.1; H 5.55; N 31.5; S 11.9.
    Example 20. (4-methyl-5-imidazolylmethylthio) -ethylamino -5-benzyl-6-methylpyrimidone-4.
    To a solution of 6 g of 5-benzyl-6-methylthiouracil and 1.06 g of sodium hydroxide in 30 ml of water, 60 ml of ethanol and 3.67 g of methyl iodide are added with cooling and stirring. The mixture is heated for 0.5 h at 60 ° C, cooled, the precipitated solid is collected and washed with water. An additional amount of solid is obtained by acidifying the filtrate to pH 4 with acetic acid. After recrystallization from ethanol, 5.33 g of 5-benzyl-6-methyl-2-methylthiopyrimidone-4 are obtained; m.p. 220-221.5 ° C.
    A mixture of 1.28 g of 5 (2-aminoethyl) -thiomethyl-4methylimidazole and 1.84 g of 5-beisyl-6-methyl2-methylthiopyrimidone-4 is heated for 4.5 hours at 150-160 ° C (bath temperature). The mixture is cooled, washed with water, recrystallized from isopropanol to obtain 1.82 g (4-methyl-5-imidazolylmethylthio) ethylamino-5-bepsyl-6-methylpyrimidone-4; m.p. 140-141.5 ° C.
    Calculated,%: C, 61.8; H 6.3; N 18.95; S 8.68.
    CigHzsNsOS.
    Paydepo,%: C 61.7; H 6.66; N 18.5; S 8.20.
    Example 21. (4-Methyl-5-imidazolylmethylthio) -ethylamino-4-HIPOLON-2.
    A mixture of 3.72 g of 2-chloro-4-ethoxyquinoline and 3.1 g of 5- (2-aminoethyl) -thiomethyl-4-methylimidazole is heated for 3 hours at 150-160 ° С (oil bapy temperature). After cooling, it is washed with water and dried. Purification was performed by chromatography (silica gel column, ethyl acetate-5% methiol eluant) and recrystallization from acetoia to obtain 1.86 g (4-methyl-5-imidazolylmethylthio) -ethylamino -4-ethoxyquinoline; m.p. 152.5-153.5 ° C.
    Calculated,%: C 63.1; H 6.5; N 16.4; S 9.4.
    Ci8H22N4OS.
    Found,%: C 63.2; H 6.5; N 16.1; S 9.1. A mixture of 1.69 g of (4-methyl-5-imidazolylmethylthio) -ethylamino-4-ethoxyquinoline and 30 ml of concentrated hydrochloric acid is boiled for 17 h. The solution is evaporated to dryness, the residue is dissolved in water and alkalized with potash. The precipitated oil is decanted, washed with water and crystallized from isopropyl-water, to obtain (4-methyl 5 - imidazolylmethylthio) -ethylamino-quinolone-4; m.p. 121 - 124 ° C.
    Calculated,%: C 61.1; H 5.8; N 17.8; S 10.2.
    C, 6Hi8N4OS.
    Found,%: C 60.1; H 5.7; N 17.1; S 9.9.
    Example 22. (4-Imidazolyl) -butylamino-thiopyrimidone-2.
    By the method described in Example 5 by the reaction of 2.8 g of 4 (5) - (4-aminobutyl) -imidazole and 1.44 g of 2,4-dimercaptopirimidine, (4-imidazolyl) -butylaminothio-pyrimidone-2 is obtained; m.p. 209-211 ° С (from and. Propanol).
    Calculated,%: C 51.6; H 6.3; N 27.35; S 12,5.
    CuHi5N5SO-4H20.
    Found,%: C 51.4; H 6.3; N 27.0; S 13.0.
    Example 23: Reaction of 2-methylthiopyrimidone-4 by the method described in Example 1 with the following compounds:
    4- (2-aminoethylthiomethyl) -imidazole,
    4- (2-aminoethylthiomethyl) -5 - bromimidazole,
    4- (3-aminopropylthiomethyl) -imidazole,
    2- (2 - aminoethylthiomethyl) -3-bromopyridine,
    2- (2 - aminoethylthiomethyl) - 3 - oxypyridipoam,
    2 - (2 - aminoethylthiomethyl) - 3 - methylpyridine,
    2 - (2 - aminoethylthiomethyl) - 3 - aminopyridine,
    2- (2 - aminoethylthiomethyl) - thiazole,
    2- (4-aminobutyl) -thiazole,
    3- (2-aminoethylthiomethyl) -isothiazole,
    3- (2 - aminoethylthiomethyl) - 4 - bromoisothiazole,
    2-amino-5- (2-aminoethylthiomethyl) 1, 3,4-thiadiazole, the following compounds are obtained:
    2 - 2 - (4 - imidazolylmethylthio) - ethylamino-pyrimidone-4,
    2 - 2 - (4 - bromo - 5 - imidazolylmethylthio) -ethylamino-pyrimidone-4,
    2 - 3 - (4 - imidazolylmethylthio) - propylamino-pyrimidone-4,
    2 - 2 - (3 - bromo - 2 - pyridylmethylthio) ethylamino-pyrimidone-4,
    2 - 2 - (3 - hydroxy - 2 - pyridylmethylthio) ethylamino-pyrimidone-4,
    2 to 2 - (3 - methyl - 2 - pyridylmethylthio) ethylamino-pyrimidone-4,
    2- 2- (3 - amio - 2 - pyridylmethylthio) ethylamino-pyrimidone-4,
    2 - - (2 - thiazolylmethylthio) - ethylamino-pyrimidone-4,
    2 to 4 - (2 - thiazolyl) - butylamino-pyrimidone-4,
    2 - 2 - (3 - isothiazolylmethylthio) - ethylamino-pyrimido-4.

    2 - 2 - (4 - bromo - 3 - isothiazolylmethylthio) -ethylamino-pyrimidone-4,
    2 - - (2 - amino - 5 - {1,3,4 - thiadiazolylmethylthio}) ethylamino-pyrimidone-4.
    权利要求:
    Claims (1)
    [1]
    1. Weigang Hilgetag. Experimental methods in organic chemistry, M., “Chemistry, 1968, p. 419.
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    同族专利:
    公开号 | 公开日
    US3932644A|1976-01-13|
    IL44526A|1979-05-31|
    AU6859874A|1975-11-06|
    NL7404811A|1974-11-05|
    SE416299B|1980-12-15|
    BE814032A|1974-10-22|
    IE40014B1|1979-02-28|
    JPS5855145B2|1983-12-08|
    DE2421548A1|1974-11-21|
    JPS5025565A|1975-03-18|
    IE40014L|1974-11-03|
    ES425936A1|1976-09-16|
    FR2227869B1|1978-07-21|
    FI62301B|1982-08-31|
    FR2227869A1|1974-11-29|
    IN138721B|1976-03-20|
    AU477220B2|1976-10-21|
    CH605917A5|1978-10-13|
    HU168863B|1976-07-28|
    IL44526D0|1974-06-30|
    CA1041108A|1978-10-24|
    GB1419994A|1976-01-07|
    FI62301C|1982-12-10|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB2106373A|GB1419994A|1973-05-03|1973-05-03|Heterocyclicalkylaminotheterocyclic compounds methods for their preparation and compositions comprising them|
    GB3555173|1973-07-26|
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