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    • 专利摘要:
    Pharmaceutical intermediates, morphine potentiators and other compounds have the formula <IMAGE> wherein R is hydrogen, halogen, C1-4 alkyl, hydroxy, nitro, amino, carboxy or a carboxylic acid derivate radical, R1 is hydrogen or a C1-4 alkyl, R2 is hydrogen or C1-4 alkyl, R3 is hydrogen, R4 is hydrogen or C1-4 alkyl, R5 is hydrogen R6 is hydrogen or R3 and R4 and/or R5 and R6 form a chemical bond, X is oxygen or imino, m is 1, 2, 3 or 4, n is 0, 1, 2 or 3, and if n is 1, then the dotted lines can stand for bonds, with the proviso that if m=1 and n=1 and if in the 2,3-, 6,7-, 8,9- and 1,10-positions double bonds are present, and R1 and R2 are hydrogen, then R is other than 9-hydroxy or 9-methyl; if m=2 and n=1 and R2 is hydrogen, then at least one of R and R1 is other than hydrogen; and if m=2 and n=2 and R2 is hydrogen and the molecule is a 2,3,4,6,7,8,9,10-octahydro derivative, then at least one of R and R1 is other than hydrogen or an acid-addition or quaternary salt thereof.
    公开号:SU749365A3
    申请号:SU782652051
    申请日:1978-08-18
    公开日:1980-07-15
    发明作者:Хермец Иштван；Фюлеп Ференц；Месарош Золтан；Бернат Габор；Кнолл Йожеф
    申请人:Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра Рт (Фирма)；
    IPC主号:
    专利说明:

    where R and ni have the indicated values
    R-J is an alkoxycarbonyl residue containing 1-4 carbon atoms in the alkyl part, or KapdOKclJibHbfCltapBoKcademide or nitrile residue. The resulting products are esterified or esterified to form compounds of the formula T, where R is an alkoxycarbonyl group.
    The desired products are isolated as bases or quaternary salts.
    The reaction of 2-aminopyridines of the formula II or their acid addition salts with cyclic oxo compounds of the general formula III is preferably carried out in the presence of polyphosphoric acid, as well as in the presence of phosphorus oxychloride.
    The condensation reaction can preferably be carried out in the presence of a tertiary amine, which is preferably pyridine, picoline, quinoline, lutidine, lepidine.
    The reaction is preferably carried out at 20-250 ° C, preferably at 80IGO C -
    After the condensation reaction in polyphosphoric acid, the reaction mixture can be diluted with water and then neutralized by cooling with an alkali solution with a concentration of 10 w / v%, and it is better to use a solution of sodium hydroxide.
    The crystalline product precipitated may be separated from the reaction mixture, for example, by filtration or centrifugation. When carrying out the condensation reaction, a solution of phosphorus oxychloride can also be used as a solvent, and thus the amount of polyphosphoric acid required can be reduced. When processing the reaction mixture, the latter is decomposed with alcohol, and from the cooled mixture the hydroxyl salt in crystalline form is precipitated, which can be separated by filtration. In the case of a cyclization reaction, which is carried out in the presence of phosphorus oxychloride, the reaction mixture can be decomposed with an aqueous solution of alkali. In this case, the cyclic compound is obtained in the form of a base. If the condensation reaction is carried out in the presence of an aromatic tertiary nitrogen-containing base, the reaction is preferably carried out at the boiling point of the base used. Then the reaction mixture is evaporated under reduced pressure and the resulting residue is recrystallized from ethyl alcohol. As a result, a hydrohalide is obtained.
    In the desired case, the base is ordinary. methods can be isolated in a free state from a hydrohalibide.
    In the preparation of quaternary salts, conventional quaternizing agents such as, for example, alkyl halides (ethyl iodide, methyl iodide, methyl chloride) or dialkyl sulfates (dimethyl sulfate, diethyl sulfate) are preferably used. The reaction can be carried out in excess of a water-reducing agent or in the presence of an inert solvent at 0–200 ° C. Non-polar aromatic hydrocarbons (benzene, toluene), halogenated hydrocarbons (chloroform, chlorobenzene), ethers (dioxane) or aprotic polar solvents (dimethylformamide), nitriles (acetic acid nitrile), nitrated hydrocarbons (nitromethane, nitrobenzene), ketones (acetone, ethyl methyl ketone), hexamethylphosphoric triamide or mixtures indicated s solvent
    Quaternary salts that are precipitated from the reaction mixture during the quaternary salt formation reaction can be isolated, for example, by filtration. Using methods known from the literature, from the derivatives of pyrido (1,2-pyrimidine corresponding to general formula I, acid addition salts can be obtained with pharmaceutically acceptable or inorganic acids from a pharmaceutical point of view. Hydrohalides can be obtained (hydrochlorides, hydrobromides, hydroiodides), and also salts with sulfuric, phosphoric, chloric, formic, acetic, citric, maleic acids, etc.
    Compounds of general formula 1 can be converted into other compounds of formula 1 using known methods in some cases. Thus, for example, compounds of Form I, containing a carboxyl group in place of R, can be converted to the corresponding ester or esterification as a result of esterification. as a result of amidation, into the corresponding amides.
    The compounds used as starting materials, which correspond to the general formulas II, III, are known compounds, commercially available, or can be obtained from these compounds by methods known from the literature.
    The invention also relates to the potential stereoisomers of the compounds of general formula 1.
    The resulting compounds have well-pronounced analgesic and enhancing the effects of mrfi properties and can be applied to the form of therapeutic painkillers. Preferred groups of the general formula G are those derivatives in which R is a hydrogen atom, a methyl radical, an ethyl radical, a chlorine atom, a bromine atom, a nitro group, an amino group, a carboxyl group, a Meioxycarbonyl residue, an ethoxycarbonyl residue or a carbamoyl RJ group - hydrogen atom or methyl radical,; hydrogen atom, methyl rad. cal, ethyl radical or tertiary butyl residue 3 s1 ohms of hydrogen, or Cd and / or R together form a bond, X represents an oxygen atom, And - 0.1 or 2, m - 1-4, as well as their salts and quaternary salts valuable compounds of the general formula 1 are the following compounds: 7-methyl-2,3-trimethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine, its salts as well as quaternary, salts of this compound, 8 -methyl-2,3-trimethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine and its salt as well as quaternary salts, 6,8-dimethyl-2, 3-trimethylene-4-oxo-4H- pyrido (1,2-a) pyrimidine and its salt, as well as quaternary salts, 6-methyl-2,3-1getramethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine and its salts, as well as quaternary salts, 2,3-pentamethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine and its salts, as well as quaternary salts, 2,3-hexamethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine and its salts, as well as quaternary salts. The compounds obtained can be used, on the one hand, as pharmaceutical preparations, and, on the other hand, as intermediates in the preparation of compounds possessing biological activity. Some of the compounds have valuable anti-inflammatory, pain-relieving, antipyretic and other properties that affect the central nervous system (sedative, hypnotic sludge, and tranquilizing effect), as well as the opposite P-effect that inhibits thrombocyte aggregation activity, anti-asthmatic activity, anti-arteriosclerotic and beneficial effects affecting blood circulation. Some representatives show a microbial-destructive effect. the development of microbes action. Particularly strong are the analgesic and morphic enhancing properties of some derivatives. The results obtained during the tests are presented in table 1. To determine the toxicity, mice were examined 48 hours after the administration of the compounds and the LDgg value was determined graphically according to Litha-ice and Wilcoxon. In the study of painkillers and enhancing the effect of morphine properties Also used mice. In tab. Table 1 presents the results obtained in the test with a hot plate, and the results obtained in the laparotomic test according to Knoll 2, Table. Table 1 also gives the corresponding values for the compared compound prob. From the table. 1 data follows that the listed compounds. nor have the excellent ability to enhance the effect of morphine. Compounds enhance similarly the effect of other morphine-like pain relievers or main pain relievers, due to which the therapeutic dose of the latter can be reduced, as a result of which adverse side effects are less observed. Tricyclic compounds of pyrido (1,2-a) pyrimidine , corresponding to general formula 1, are used as biologically active substances in preparations containing inert, non-toxic, solid or liquid diluents or carrier substances. The preparations may be in solid form (tablets, capsules, dragees) or in liquid form (e.g., solutions, suspensions, emulsions). Conventional substances (for example, talc, calcium carbonate, magnesium stearate, water, polyethylene glycolate, etc.) should be used as carriers. In the desired case, the preparations may contain obelknye additives, for example, a means of contributing to the destruction, emulsifier, etc. Tricyclic pyridium (1,2-a) pyrimidine compounds of general formula I can be contained in the above preparations together with other painkillers such as morphine derivatives (morphine, azidomorphine, azidocodein), morphine derivatives, benzomorphane derivatives (phenazocine, pentazocine), derivatives phenylpiperidine (petiine, nizentil), etc. The latter prozvodnye due to their synergistic effect is used in smaller doah, thanks to what can adversely be eliminated
    side effects of these compounds (tolerance, passive dependence, difficulty breathing).
    Examples - 20. 20. Mole 2-ethoxycarbonyl-1-oxocycloalkane listed in table. 2, and 20. mol of α-aminopyridine are stirred in 20 g of polyphosphoric acid for 0 min at 100 ° C. The reaction mixture is then diluted with 20 ml of water and, after cooling, the pH of the mixture is adjusted to 7 by addition. Sodium hydroxide solution with a concentration of 10 w / v%. The crystalline product precipitated in the precipitate was filtered, washed with a small amount of water and then dried. The pyrido (1,2-a) pyrimidine compound obtained is recrystallized from the indicated solvent.
    The compounds obtained and their physical characteristics are presented in table. 2
    Examples 21 -35. 0.1 mol specified in table. 3 2-ethoxycarbonyl-1-oxocycloalkane and 0.1 mol of 2-aminopyridine are mixed in a mixture of 28 ml of phosphorus oxychloride and 7.0 g of polyphosphoric acid for .3 h at 100 ° C. The reaction mixture is decomposed with 100 ml of ethanol at 70, -. The mixture is then cooled and the precipitated hydrochloric salt is filtered off, washed with ethyl alcohol, dried and recrystallized from the indicated solution.
    The compounds obtained and their physical characteristics are presented in table. 3
    Example 36 15.6 g of 2-ethoxycarbonyl-1-oxocyclopentane and 10.8 g of 2-amino-6-methylpyridine are stirred for 3 hours in a water bath in a mixture containing 28 ml of phosphorus oxychloride and 7.0 g of polyphosphoric acid . The reaction mixture is then cooled and, when cooled outside, carefully decomposes 50 ml of water, after which the mixture is neutralized by adding sodium hydroxide solution with a concentration of 10% w / v. The oily product which has precipitated out is crystallized by trituration. The obtained crystalline product is filtered, washed with water, dried and recrystallized from ethyl alcohol. As a result, 17 g (85%) of 2,3-dimethylene-b-methyl-4-oxo-4H-pyrido {1, 2-O) pyrimidine, which has a melting point, are obtained. ISO-iei C. The resulting product does not depress the melting point when mixed with the product obtained in accordance with example
    21 .; .
    PRI me R 37. 0.02 mol of hydrochloride 2-Ash-1N-pyridine is heated for 16 hours in 50 ml of pyridine with
    0.03 mol of 2-ethoxycarbonyl-1-oxocyclopentane at reflux temperature of the reaction mixture. Then, the solvent and unreacted 2-ethoxycarbonyl-1-oxocyclopentane are distilled off from the reaction mixture under reduced pressure and the resulting residue is crystallized from a mixture of ethyl alcohol and diethyl ether. The result is 2.15 g (48%) of 2,3-Trimethylene-4-oxo-4H-pyrido hydrochloride (1,2 pyrimidine. The resulting product has a melting point of 222-224 ° C. And does not give a melting point depression at it is mixed with the product obtained in accordance with example 22.
    Example 38. The method is carried out by analogy with that described in Example 37; however, instead of 2-aminopyridine hydrochloride, hydrobromide-2-aminopyridine is used, and after carrying out the reaction for 8 hours, 3.3 g (62 g) are obtained. %) 2,3-trimethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine hydrobromide. After recrystallization from ethyl alcohol, the product has an mp. 275-277 ° C;
    Calculated,%: C 49.46, H 4.15, N 10.49, Br 29.91.
    StsNtsM VgO.
    Found,%: C 49.80, H 4.37, N 10.62, Br 29.85.
    A base is recovered from the hydrobromide salt in a free state using a conventional method, which is recrystallized from ethyl alcohol. The result is 2,3-trimethylene-4-oxo-4H-pyrido (1,2-01) pyrimidine, which does not depress the melting point when it is mixed with the product obtained in accordance with Example 1.
    PRI me R 39. The method was carried out by analogy with that described in Example 37, however, instead of 2-aminopyridine hydrochloride, 2-aminopyridine hydroiodide is used. After reacting for 6 hours, 4.74 g (76%) of 2,3-trimethylene-4oxo-4H-pyrido (1,2-a) pyrimidine hydroiodide are obtained, which, after recrystallization from ethyl alcohol, has m, pl. 212-214 ° C.
    Calculated,%: C 42.06, H 3.53, N 8.92, 3 40.40.
    CjjHiiNglO.
    Found: C, 41.85; H, 3.60; N, 9.09.3, 40.21.
    Example 40 2.0 g of 2,3-trimethylene-6-methyl-4-oxo-4H-pyrido (1,2-a) pyrimidine is dissolved in 25 m of acetone and the prepared solution together with 7.1 g of methyl iodide is placed into a refractory ampoule. Placed vial incubated for 10 h at. After cooling and opening the ampoules, its contents are evaporated to 15 ml. The mixture is kept in. Overnight and the precipitated crystalline product is then filtered and treated with a small amount of acetone. As a result, 2.15 g (67%) of the yellow iodide of 1,6-dimethyl-2, 3-trimethylene-4 - ;; oxo-4H-pyrido (1, 2-a) pyrimidine, yellowed; which, after recrystallization from ethyl alcohol, has a melting point of 228-230 ° C. Calculated,%: C 45.63, H 4.42. , 5N2 OD. Found,%: C 45.62, H 4.43. Example41. 4.0 g of 2, 3-trimethylene-6-methyl-4-oxo-4H-pyrido (1,2-a) pyrimidine is dissolved in 50 ml of acetone and the mixture obtained after adding 2.52 g of dimethyl sulfate is heated for 16 h at boiling point. The volume of the reaction mixture is then reduced by approximately evaporation by about half. Upon cooling, precipitation of the crystalline product occurs. The resulting crystalline product is filtered and washed with acetone. As a result, 4.96 (76%) methylsulfate 1,6-dimethyl-2, 3-trimethylene-4-oxo-4H-pyrido (1,2-a) pyrimidine is obtained, which after recrystallization from a mixture of ethyl alcohol and diethyl ether has so pl. 148-150s. Calculated,%: C 51.52, H 5.56, N 8.58. Found,%: C 51.98, H 5.58, N 8.53. Example 42 15.6 g of 2-ethoxycarbonyl-1-oxocyclopentane and 11.1 of 2-amino-3-hydroxypyridine are reacted by analogy with that described in example 36, resulting in 10.2 g of 2-3- Trimethylene-9-ox-C1-4-oxo-4H-pyrido (1,2-a) pyrimid in the form of a crystalline substance, which has a mp. 152-15bs. After recrystallization from 70% ethyl alcohol, the product does not give a compression of the melting point when mixed with the product, according to Example 6. EXAMPLE 43. 2-hydroxy-4-methyl-pyridide hydrochloride as described in β-example 37, is reacted with 2-ethoxycarbonyl-1-oxo-cyclopentane, resulting in 2.08 g (44%) of 2,3-trimethylene-8-methyl-4-oxo-4H-pyrido hydrochloride (1, 2-a) pyrimidine, which has m. Pl. 200-205 C, and the product does not give a depression to the melting point when it is mixed with the product obtained in Example 24. Example 44.0.02 mol 2-ethoc of sycarbonyl-1-oxocyclohexane, enter into interaction with 0.02 mol 2-am of nonicotinic acid according to analogies with those described in examples 1-20. 2, 3-tetramethylene-9-carboxy-4-oxo-4H-pyrido (1,2-a) pyri, midin are obtained in a recipe in 46% yield. After recrystallization from ethyl alcohol, the product has a melting point of 200 202-204 ° C. Calculated: C 63.52, H 4.95,,. Found,%: C, H 4.95. , Example 45. By analogy with Examples 1-20, 0.02 mol of 2-ethoxycarbonyl-1-oxocyclohexane is reacted with 0.02 mol of 2-amino-3-ethoxycarbonylpyridine. as a result, with a yield of 63%, 2,3-tetramethylene-9-ethoxycarbonyl-4-oxo-4H-pyrido (1,2-a} -pyrimidine) is obtained. After recrystallization from ethyl alcohol, the melting point is 143-1.44 s. Calculated,%: C 66.16, H 5.92. CijHi NgO. Found,%: C 66.20, H 5.87. Example 4g. 1 g obtained according to apr; 1mersh 45 2,3-tetramethylene -9-carboxy-4-oxo-4H-pyrido (1,2-a) - pyrimidine is heated for 3 hours at the boiling point of the reaction mixture under reflux in 20 ml of ethyl alcohol containing 20% w / v hydrochloric acid. Then the solution is evaporated, with the result that I get a yellow colored crystalline substance which is dissolved in 25 ml of water. The solution obtained is neutralized with a saturated solution of sodium carbonate. The result is 2,3-tetramethylene-9-ethoxycarbonyl-1-oxo-4H-pyrido (1,2-st) pyrimidine (0.92 g, 82%). The product obtained after recrystallization from ethyl alcohol has a melting point of 144-145 C. The resulting product does not depress the melting point when mixed with the product obtained in Example 45. Example 47. 0.02 mol of 2-ethoxycarbonyl-1-oxocyclohexane is reacted by analogy with that described in examples 1-20 with 0.02 mol of 6-aminonicotinic acid amide. As a result, 2,3-tetramethylene-7-carbamoyl-4-oxo-4H-pyrido (1, 2-a) -pyrimidine is obtained in a yield of 41%. After recrystallization from ethyl alcohol, m.p. product is 313-315C. Calculated,%: C64.18, H5.39, N 17.28. 13 13 3 2 Found: C, 64.22; H, 5.61. PRI me R 48. By analogy, with written in examples 1-20 0.02 mol. 2-ethoxycarbonyl-1-oxocyclohexane is added under the interaction with O, 02 mol of 2-amino-5-ethoxycarbonyl pyridine. As a result, 2,3-tetramethien-7-ethoxycarbonyl-4-oxo-4H-pyrio (1,2-a) pyrimidine is obtained. The yield of the product is 67%. After recrystallization from diethyl ether, the product has an mp. 100-1Q2 ° C. Calculated,%: C 66.16, H 5.92.
    CijHi MgO.
    Found: C 66.20, N.
    Example 49. By analogy with opian in Example 36, 0.02 mol of 2-ethoxycarbonyl-1-oxocyclohexane is introduced into the reaction with 0.02 mol of 6-aminonicotinic acid. As a result, 2,3-tetramethylene-7-car-oxy-4-oxr-4H-pyrido (1,2-a) pyrimidine is obtained. Exit 44%. After recrystallization from ethyl alcohol, the product has a melting point of 207 256-258s,
    Calculated,%: C 63.92, H 4.95.
     er
    Found,%: C 63.84, H 5.00,
    Example 50. 0.02 mol of 2-ethoxycarbonyl-1-oxocyclohexane and 0.02 mol of b-aminonicotinic acid are stirred for 2 hours while in a mixture of 10 ml of chlorophosphate and 2 g of polyphosphoric acid. Then the reaction mixture is decomposed with TO-vO of 20 ml of ethyl alcohol. The solution, while cooling with ice, is neutralized with sodium hydroxide solution with a concentration of 10% w / v. Ethyl alcohol was removed by distillation, the residue was extracted with chloroform (4x25 ml). The combined extracts are dried and then evaporated. The residue is triturated with diethyl ether, 6 causing the product to crystallize. 2,3 tetramethylene-7-ethoxycarbonyl-4-oxo-4H-pyrido (1, 2-o) pyrimidine is obtained. Yield 40%. After recrystallization from diethyl ether, a product is obtained with m.p. 10 -102c, which does not result in depression of the melting point with the product obtained in Example 48.
    Example 51. By analogy with Example 51, 0.02 mol of 2-ethoxycarbonyl-1-oxocyclohexane is introduced.
    in the interaction with 0.02 mol of 2-amino-5-ethoxycarbonylpyridine. The result is 2, 3-tetramethylene-7-ethoxycarbonyl-4-oxo-4H-pyrido (1,2-a) pyrimidine. Yield 49%. After recrystallization from diethyl ether, m.p., the P1 product is 100-102 seconds, and the product does not depress the melting point when it is mixed with the products corresponding to dimmes 48 and 50.
    and:
    Example 56. A 2,3-tetra-1-methylene-7-carboxy-4-oxo-4H-pyrido (1,2-a) pyrimidine prepared according to Example 50 is etherified.
    5 ethyl alcohol by analogy with that described in Example 81. As a result, 2,3-tetramethylene-7-ethoxycarbonyl-4-oxo-4H-pyrido (1,2-o) pyrimidine is obtained. Yield 91%, T. pl. after
    0 recrystallization from ether 101102 С. The product does not depress the melting point with the products obtained in Examples 48, 50 or 51.
    Example 53: 2.82 g (0.02 mol). 2-oxocyclohexane-1-carboxamide and 1.88 g (0.02 mol) of 2-aminopyridine are heated for 1.5 hours while stirring in 20 ml of polyphosphoric acid in water Noah bath. The reaction mixture is pouring-. 20 ml of water and neutralized with sodium hydroxide solution with a concentration of 10% by weight. The resulting crystalline product is filtered and washed with water. The result is 2.6 g (46%) of 2,3-tetrame, tylen-4-oxo-4H-pyrido (1, 2-a) pyrimidine, which is recrystallized from diisopropyl ether.
    0 T. pl. . The product does not depress the melting point when mixed with the product obtained in accordance with Example 12.
    dp
    I
    o (BUT)
    q an
    S "s
    -n and with about
    p m about g
    Sri
    iso
    Xi.
    I
    OooX o a:
    iooo R 1v
    SPA I
    X n x
    I (wto
    (NXI
    l r
    n
    00
    in
    T- (
    l
    T
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    VO
    ts
    n
    PM
    权利要求:
    Claims (7)
    [1]
    H. Claim 1. Method for the preparation of 2,3-polymeth le-4-oxo-4H-pyrido (1, 2-q) pyrimidines of general formula I: Bi Bit BS BZ, "t-I I (ng). where R is hydrogen, halogen, C alkyl, hydroxy, nitro, karsi, C - Cd-alkoxycarbonyl or carbamoyl, R - hydrogen or C - C. - al Rg - hydrogen or Cj - al Rj - hydrogen, R - hydrogen or C is al RC and R-hydrogen, or Rg and, I and R form a bond, m 1,2,3 or 4, provided that h in the case when w 1 and in x 2, 3, 6,7,8,9 and 1,10 is double. the bond and RI to 2 are hydrogen then R does not mean 9-hydroxy or 9-methi group, or in the case when tn 2 and R are hydrogen, then at least one of the symbols R and Rj. does not mean hydrogen, or their quaternary salts, which is different from the fact that a 2-aminopyridine derivative of general formula II is Ti where R and RI have the indicated values or its acid addition salt is reacted with an oxo compound of general formula III (y ) "(T}. Where R and L1 have the indicated meanings, R is an alkoxycarbonyl residue containing 1-4 carbon atoms in the alkyl part, or a carboxyl, carboxamide or nitrile residue, followed by isolation of the target product or followed by esterification of the resulting product to obtain Neny formula 1, wherein R - alkoxycarbonyl group, and isolating the desired produ KTA in the form a base or salt .chetvertichnoy..
    [2]
    2. A method according to claim 1, characterized in that the process is carried out in the presence of polyphosphoric acid.
    [3]
    3. Method according to paragraphs. 1 and 2, that is, that the process is carried out in the presence of phosphorus oxychloride.
    [4]
    4. A method according to claim 1, wherein the process is carried out in the presence of a tertiary amine.
    [5]
    5. The method according to claim 4, characterized by the fact that pyridine, picoline, quinoline, lutidine or lepidine is used as a tertiary amine. ..
    [6]
    6. Method according to paragraphs. 1-5, characterized in that the process is carried out at 20-250 ° C.
    [7]
    7. Method according to paragraphs. 1-5, characterized in that an alkyl halide or a dialkyl sulfate is used to obtain a quaternary salt. Sources of information taken into account in the examination 1.Bowden Co. Brown Brown TN The Reaction of 2-Amipore Gidine with Some / 6-Keto-esters in the Presence of PoJyposphori Acid Ethye Ester-J. Chem. Soc. C, 1971, p. 2163. 2, Aminal aud Clinical Pharmccologic Technigues in Drug Evaluation, Year Book Publ. Chicago, 1967, Vol. 2, p. 305-321.
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    同族专利:
    公开号 | 公开日
    YU196578A|1983-10-31|
    SE7808771L|1979-02-20|
    DD138902A5|1979-11-28|
    DE2836449A1|1979-03-22|
    CA1117525A|1982-02-02|
    DE2836449C2|1990-09-06|
    JPS5459299A|1979-05-12|
    CS541878A1|1985-05-15|
    FI782517A|1979-02-20|
    AT371818B|1983-08-10|
    DK157021B|1989-10-30|
    PL116688B1|1981-06-30|
    ATA597178A|1982-12-15|
    FI67547B|1984-12-31|
    FI67547C|1985-04-10|
    GB2003870B|1982-07-21|
    US4220771A|1980-09-02|
    CH638207A5|1983-09-15|
    HU182009B|1983-12-28|
    BE869833A|1978-12-18|
    FR2416893A1|1979-09-07|
    SE436279B|1984-11-26|
    CS240351B1|1986-02-13|
    NL7808571A|1979-02-21|
    DK157021C|1990-04-02|
    ES473182A1|1979-04-01|
    DK367378A|1979-02-20|
    PL209131A1|1979-06-04|
    GB2003870A|1979-03-21|
    GR65275B|1980-07-31|
    FR2416893B1|1983-07-22|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU77CI1766A|HU182009B|1977-08-19|1977-08-19|Process for producing substituted pirido-square bracket-1,2-a-square bracket closed-pyrimidines, pyrrolo-square bracket-1,2-a-square bracket closed-pyrimidines|
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