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    1427945 Derivatives of 3-aminopyrrole GRUPPO LEPETIT SpA 25 July 1974 [22 Aug 1973] 39790/73 Heading C2C The invention comprises compounds of formula and their salts with pharmaceutically acceptable acids, wherein R is hydrogen, (C 1-4 )alkyl, benzyl or halo-substituted benzyl; R 1 is hydrogen, (C 1-4 )alkyl, phenyl or phenyl carrying one to three substituents chosen from (C 1-4 )alkyl, (C 1-4 )alkoxy, benzyloxy, fluoro, chloro, bromo, hydroxy and nitro; R 2 is hydrogen, (C 1-4 )alkyl, formyl, (C 2-4 )aliphatic acyl, benzoyl, carbo- (C 1-4 )alkoxy -(C 2-4 )aliphatic acyl, carbamyl, phenylcarbamyl, thiocarbamyl, phenylthiocarbamyl, benzoylthiocarbamyl, carboxyphenyl, benzenesulphonyl, (C 1-4 )alkylsulphonyl, toluenesulphonyl or phenacylsulphonyl; R 3 is hydrogen or (C 1-4 )alkyl or R 2 and R 3 together are (C 2-4 )alkylidene, benzylidene or halo-substituted benzylidene; R 4 is (C 2-4 )- aliphatic acyl, benzoyl, benzoyl carrying one to three substituents chosen from fluoro, chloro, bromo and (C 1-4 )alkoxy, carbo(C 1-4 )alkoxy, carboxy, carbamyl, methylcarbamyl or phenylcarbamyl and R 5 is hydrogen, (C 1-4 )alkyl, carbo(C 1-4 )alkoxy, carbo (C 1-4 )alkoxy-methyl, trifluoromethyl, carboxy, carbamyl or carbazoyl or R 4 and R 5 together are -CO-(CH 2 ) n -, wherein the carbonyl group is connected to the carbon atom of the pyrrole ring which bears the substituent R 4 and n is 2, 3 or 4, provided that when R 1 =R 5 =Me and R=H, then one of R 2 , R 3 #H and R 4 #CO 2 Et. These compounds are prepared (when R=R 2 =R 3 =H) by reacting RNH-CHR 1 -CN with either R 2 COCH 2 R 4 or R 5 C # CR 4 and cyclizing the thus formed inter-- mediate of formula the products may then be reacted further if desired to convert the 3-NH 2 groups or other functional groups present to different substituent groups and/or replace the 1-H atom by R(#H). Therapeutic compositions having anti-inflammatory antipyretic and analgesic activity, C.N.S. depressant activity, and in some cases sedative and myorelaxing activity, comprise compounds of the above formula, and may be administered orally, parenterally or rectally.
    公开号:SU843738A3
    申请号:SU742055571
    申请日:1974-08-21
    公开日:1981-06-30
    发明作者:Гарциа Джорджо；Панцоне Джанбаттиста
    申请人:Группо Лепетит С,П.А. (Фирма)；
    IPC主号:
    专利说明:

    one
    This invention relates to the preparation of new 3-aminopyrro derivatives of general formula (I)
    Bs r
    vt
    5 il)
    I
    R
    whether its salts with pharmaceutically acceptable acids,
    hydrogen, (C.l) -alkyl,
    de R benzyl or halogen substituted benzyl; hydrogen, (,) -alkyl, phenyl or substituted by a halogen atom, or methyl, or methoxy groups, phenyl; hydrogen, (C,) -alkyl, formyl, (C) - aliphatic adyl, benzoyl, carboethoxyacetals, carbamyl, phenylcarbamyl, thiocarbamyl, phenylthiocarbamyl, 1Venzoylthiocarbamyl, carboxyphenylbenzulfonyl, methylsulfone, aeyeher, aequatone, thiocarbamyl, carboxyphenyl benesulfonyl, methylsulfone, aequiatype, nitrocarbamyl, carboxyphenylbenesulfonyl, methylsulfone, and anhydrohydrocarbamyl, carboxyphenyl benesulfonyl, methylsulfone, and anhydroxy sulfonyl, nitrocarbamyl, carboxyphenyl benesulfonyl, methylsulfone, hydrochloromethylthiophenylcarboxylic acid hydrogen or (C.j) -alkyl;
    (Cg./,) -aliphatic acyl benzoyl, substituted by chlorine atom or methoxy group, benzoyl, carbo- (C) -alkoxy,
    0 carboxy, carbamyl, methylcarbamyl or phenylcarbamyl hydrogen, (C4.i) - alkyl, carbo- () -al5 coxy, carboethoxymethyl, trifluoromethyl, carboxy, carbamyl or carbazoyl;
    together - (,) -il kiliRO. and R,
    0 den, benzolidinone or substituted by chlorine atom benzolidin; together the group —CO — CH “CdI Rg, where the carbonyl portion is bound to the carbon atom of the pyrrole ring containing the substituent R, with 1 RgtH and R“ H
    0 one of the radicals R or RIJ, should not be hydrogen, and Rj. not until women are carboethoxy. 3-aminopyrrole derivatives and their salts with pharmaceutically acceptable acids are biologically active compounds. These compounds and their properties are not described in the literature. There are known methods for the synthesis of pyrrole derivatives by the interaction of oi -amine carbonyl compounds and compounds containing methylene groups in the os position to the carbonyl group 1 and 2. The proposed method allows new derivatives of 3-aminopirone, which MOFyT can be used as medicinal means. According to the invention, the 3-aminopirrus of the indicated general formula (I) with, 2 Rnj H or their salts are obtained by the interaction of (α-aminonitrile with the general formula (II) CN. CH. 00 or its acid additive salt, where R has the above value, with a compound of the general formula (IW where R ' and RC have the above values, and the X group or the group —GHfj — Cj.-, where —CHj is part bound to the substituent R. The reaction is usually carried out in an anhydrous organic solvent, for example in benzene, dioxane, tetrahydrofuran or in alcohols at an equimolecular ratio of the initial reagent Combustion. If necessary, p-toluenesulfonic acid is used as a catalyst.The reaction is carried out with heating for 2-28 h. The intermediate compound of the general formula ((V) CN X. L B & I) is isolated and then cyclized to the corresponding aminopyrrol of formula (I) in the presence of basic catalysts, such as carbonates, hydroxides, alkoxides, hydrides or amides of metals of the I and M groups of the periodic Mendeleev system, In this case, alkanols with carbon atoms not more than 4, and the reaction is carried out at If the reaction is carried out with a compound (and I) in which X is -CsC-, then intermediate (IV) is not isolated and the condensation is carried out in one stage. Anhydrous (C) -alkanol, chloroform, tetrahydrofuran, benzene or their analogues are used as a solvent, carbonates or hydroxides of alkali or alkaline earth metals are used as a catalyst. The reaction is carried out by heating for 3-5 hours. The desired products are isolated by conventional methods in the form of bases or their salts with pharmaceutically acceptable acids and the corresponding hydrochlorides, hydrobromides, hydroiodides, sulfates, phosphates, benzoates, oxalates, acetates, methanesulfonates, cyclohexylsulfonates are obtained. and their analogues. Of the salts, the free bases are obtained by treating them with an equimolar amount of the base. 3-Aminopyrrols of the general formula (I), where Rjj and R do not mean hydrogen, are obtained from the compound of formula (I), with R2 RTj H, by acylation, alkylation, sulfonylation, carbamylation, thiocarbamylation, formation, arylation, formation of Schiff bases. For example, a 3-aminopyrrole of the formula (|) is reacted with RR, 2 Rj H with (Cj) alkyl halides, di (.) Alkyl sulfates, formic acid mixtures and formaldehyde, monohalides (Cj.g) dicarboxylic acids where the second carboxyl group is esterified into ester (C,) alkanol idols, formic acid, alkali metal cyanates or thiocyanates, phenylisocyanate, aphyl acetate, cyanate, benzoylisotio cyanate, benzoic acid, substituted by an halogen atom in an aromatic ring, (Cj.i) aliphatic aldehyde Y (and, (C)) aliphyde, (Cj.i) aliphatic aldehyde U (and, (C)) aliphyde, (Cj.i) a ring by halogen atoms. 3-aminopyrrole compounds of formula (I) with R- other than hydrogen are obtained by reacting a compound of formula (|), where R is hydrogen with (C.) a) alkyl halide, benzyl or with a substituted benzyl halide in the presence of a strong base, for example an alkali metal, or an alkali metal hydride in an inert organic solvent such as dimethylformamide under a nitrogen atmosphere. The reaction is carried out at room temperature. If the reaction is carried out with compounds of formula (I), where one or both of the radicals R or R are hydrogen, then they can also be substituted by the substitutes listed above. To obtain the desired products with a free amino group, in the third position and K-different from hydrogen, first protect the amino group by conventional methods, then carry out the reaction in position 1 of the pyrrole ring and remove the protection of the amino group in the usual way. 3-aminopyrrole general formula. (I) where R is hydrogen, R, j is hydrogen, and RIV is (,) is an alkyl group, derived from a compound of formula (I), where, by preliminary sulfonylation of the amino group, followed by alkylation of the monosubstituted amine. The sulfonyl group is removed by acid hydrolysis by known methods. The radicals R and Rg can be converted by chemical reactions into other groups. For example, if a compound of structural formula (I) is required, where either one of the symbols Rd and Rgg or both represent a carboxyl group, it is obtained by hydrolysis under basic or acidic conditions of the corresponding mono- or dicarboxylic (,) alkoxy group . In addition, compounds of structural formula (I), where one or both of the radicals R and R are carbamyl groups, are obtained by saturating the alcoholic solution of the corresponding mono- or dicarbo- (C.j ;,) alkoxysolenoses with ammonia. The 3-aminopyrrols of formula (I), where Rg is carbazoyl, are obtained by the interaction of hydrazine with compounds of structural formula (I), where RS is carbo- () alkoxy, at room temperature. These 3-aminopyrroles and their salts are pharmacologically active compounds. Example 1. Preparation of 4-acetyl-3-amino-5-methyl-2-phenyl-propol-hydrochloride a. a) A solution of 2 g (0.015 mol) of 2-amino-2-phenylacetonitrile and 1, -4 g (0.014 mol) of acetylacetate in 30 ml of anhydrous benzene is heated under reflux on an oil bath in the presence of 100 mg of o-toluenesulfonic acid. After cooling, the reaction mixture is filtered, the solvent is distilled off, the resulting oily residue of the intermediate compound is distilled under reduced pressure at 150 ° C / 0.1 mm Hg. Art. b) 0.40 g of sodium is dissolved in 15 ml of anhydrous ethanol, then a solution (2.5 g) of the compound obtained as described in section a in anhydrous ethanol is added dropwise, the mixture is kept at room temperature for 4 hours. After passing dry hydrogen chloride to an ethanol solution, a precipitate formed, which was isolated by filtration. The recrystallization was carried out from ethanol-diethyl ether. Output 2.0 g, so pl. 242 ° C (with decomposition), the free base is obtained by extraction with ethyl acetate of an aqueous solution of hydrochloride, alkalized with sodium hydroxide (5%), so pl. (from methanol). Example 2. Obtaining 3-amino-4-carbethoxy-5-methyl-2-phenyl-pyrrol-hydrochloride. a) A solution of 6 g (0.042 mol) of 2-amino-2-phenylacetonitrile and 5 g (0.042 mol) of ethylacetoacetate in 30 ml of anhydrous benol is heated under reflux for 4 hours in an oil bath in the presence of 100 mg of p-toluenesulfonic acid. Upon cooling, the reaction mixture is filtered, the solvent is distilled off, the resulting oily residue is distilled under reduced pressure at, 05 mm Hg. b) 0.80 g of sodium is dissolved in 15 ml of anhydrous ethanol, then a solution (5 g) of the above-described compound is added dropwise in 35 ml without aqueous ethanol, the mixture is kept for 4 hours at room temperature. By passing dry hydrogen chloride into an ethanol solution, a precipitate is formed, which is filtered and recrystallized from a mixture of ethanol and diethyl ether. Yield 4 g, so pl. 249-252 s (from ethanol / ethyl ether). The following compounds are prepared analogously to Example 1, starting from a variety of compounds of structural formulas (I1) and (III) using alkali metal alkoxides or carbonates as the main cyclization catalyst. If intermediates IV are isolated, their physicochemical properties are reduced, otherwise it is assumed that these intermediates directly cyclize into the desired products. Example 3. Obtaining 3-amino-4-benzoyl-5-methyl-2-phenyl-pyrrole-hydrochloride. Starting from 2-amino-2-phenyl-acetonitrile and benzoyl acetone, a branched intermediate with a melting point is obtained. 134-135s (from diethyl ether / hexane). The output of the hydrochloride 60%, so pl. 285-290С (from methanol / diethyl ether). T. pl. free base 203-205C (from methanol). Example 4. Obtaining 3-amkno-6, 7-dihydro-2-phenyl-indole-4 (5H) -one hydrochloride. Starting from 2-amino-2-phenyl-acetonitrile and cyclohexane-1,3-dione, a branched intermediate is obtained, mp. 138-140s (from benzene). Output after cyclization 58%, so pl. 290-291 ° C (from ethanol / diethyl ether). Example 5 Preparation of 3-amino-4-benzoyl-2-phenyl-pyrrole-hydrochloride. Branched intermediate compound with so pl. 88-90s (from hexane is obtained from 2-amino-2-phenyl-acetoneItril and benzoylacetaldehyde. Yield after cyclization 47%, so pl. 272-274 0 (from ethanol). Example 6. Obtaining 4-acetyl-3-amino -2-ethyl-5-methyl-pyrrole-hydrochloride., Starting from 2-amino-butyronitrile and acetylacetone, a branched intermediate is obtained, ie, 10,000 / 0.02 mm Hg Total yield of the left product after cyclization 49%, m.p. 254-248C (from ethanol / distil ether). Mp of free base 219-221c (from methanol Example 7. Preparation of 3-amino-4-carbethoxy-2-phenyl-pyrrole- hydrochloride A. Named connected e is prepared from 2-amino-2-phenyl-acetonitrile and ethyl propionate in 45% overall yield, mp 244-245c (from ethanol / diethyl ether). Example 8. Preparation of 3-amino-4-benzoyl-5- carbethoxy-2-phenyl-pyrrole-hydrochloride. The named compound is obtained from 2-amino-2-phenyl-adonitrile and benzoyl-pyridinic acid ethyl ester, mp 2182190s (from ethanol / diethyl ether). Example 9. Preparation of 4-acetyl-3-aminr-2-phenyl-pyrrole-hydrochloride. Starting from 2-amino-2-phenylacetonitrile and acetylacetaldehyde, a branched intermediate compound is obtained, t. Bale. 140C / 0.05 mmHg Total product yield after cyclization is 56%. T. pl. not lower than 335 ° C. njtP-Imer 10. Preparation of 4-acetyl-3-amino-2- (p-methoxyphenyl) -pyrrole. Starting from 2-amino-2- (p-methoxyphenyl) -acetonitrile and acetylacetaldehyde, get a branched intermediate product, so Kip. 1800С / 0.03 mm Hg Art. The total yield of the product after cyclization 44%. T. pl. 198 200®C (from diethyl ether). Example 11. Preparation of 3-C1mino-benzoyl-5-methyl-pyrrole-hydrochloride. Starting from aminoacetonitrile and benzoyl acetone, a branched intermediate is obtained with a mp. 111-112 ° C (from diethyl ether). The total yield of the product after cyclization 52%, so pl. 225-270 C (from ethanol / diethyl ether). Example 12. Preparation of 4-acetyl-3-amino-5-methio-pyrrole-hydrochloride a. Starting from aminoacetonitrile and acetylacetone, a branched intermediate is obtained with a mp. Yub-SE with (from diethyl ether). The total yield of the product after cyclization 64%, t, pl. 211-212 C (from ethanol). . . Example 13: Preparation of 3-amino-4-carbethoxy-5-carbatetocoimethyl -2-phenyl-pyrrole-hydrochloride. The title compound was prepared from 2-amino-2-phenyl-acetonitrile and 1,3-dicarbethoxyacetone in 42% yield. T. pl. 232-23b C (from diethyl ether / ethanol). Example .14. Preparation of 4-acetyl-3-amino-5-methyl-2- (p-tolyl) -pyrrole. The title compound is obtained and; 2-amino-2- (p-tolyl) -acetonitrile and acetylacetone with a yield of 94%, so pl. 232-234 0 (from ethanol / diethyl ether). Example 15. Obtaining 4-acetyl-3-amino-2- (p-methoxyphenyl) -5-methyl-pyrrole. The title compound was prepared from 2-amino-2- (p-methoxyphenyl) -acetonitrile and acetylacetone in 92% yield, mp. 222-223 0 (from ethanol). Example 16. Obtaining 3-amino-4-carbethoxy-5-methyl-2- (p-tolyl) -pyrrole-hydrochloride. Starting from 2-amino-2- (l-tolyl) -acetonitrile and ethyl acetoacetate, a branched intermediate compound is obtained with m.p. 160Oo / 0.05 mm Hg. Art. The overall yield of the product after cyclization is 88%. T. pl. 266-268 O (from methanol). Example 17. Preparation of 3-amino-4-carbethoxy-2-phenyl-5-trifluoro-pyrrole-hydrochloride. The title compound was obtained from 2-amino-2-phenyl-acetonitrile and trifluoroacetyl ethyl acetate in 52% yield; mp. 203-205 0 (from ethanol). Example 18. Preparation of 4-aceyl-3-amino-2- (p-fluorophenyl) -5-methyl-pyrrole. Starting from 2-amino-2- (p-fluorophenyl) acetonitrile and acetylacetone, a branched intermediate compound, t. Kip. 1500 / 0.3 mm Hg The yield of the product after cyclization 47%, so pl. 211-212 ° C (from this nola).
    Example 19. Obtaining 3-C1-4-carbethoxy-2- (p-fluorophenyl) -5-methyl-pyrrole-hydrochloride.
    The branched intermediate is prepared from 2-cc-2- (p-fluorophenyl) -acetonitrile and ethyl acetoacetate. T. Kip. , 2 mm Hg The total yield of the product after cyclization is 53%, m.p., 258-260s (from ethanol / diethyl ether). .
    Example 20. Obtaining 3-amino-4-carbethoxy-5-methyl-pyrrole-hydrochloride.
    The branched intermediate is obtained from amino acetonitrile and ethyl acetoacetate. T. pl. 90980s (from methanol). The total yield of the product after cyclization is 44%. T. pl. 211-214C (from methanol).
    Example 21. Obtaining 3-amino-4-isobutyryl-5-methyl-2-phenyl-pyrrole.
    The branched intermediate is obtained from 2-amino-2-phenyl-acetonitrile and 5-methyl-hexane-2,4-dione, T. bale. 3 mmHg The total yield of the product after cyclization is 64%, mp. 180-183 ° C (from methanol / diethyl ether).
    Example 22. Preparation of 3-amino-5-methyl-2-phenyl-4-propionyl-pyrrole.
    Starting from 2-amino-2-phenyl-acetonitrile and hexane-2,4-dione, get a branched intermediate compound with so Kip. 1 ° C / 0.3 mm Hg The total yield of the product after cyclizadny 53%, so pl. 166-168 C (from methanol)
    Example 23. Preparation of 4-acetyl-3-amino-5-methyl-2- (meta-tolyl) -pyrrole.
    Starting from 2-amino-2- (m-tolyl) -acetonitrile and acetylacetone, a branched intermediate compound is obtained, i.p. 170C / 0.02 mmHg
    Overall, the product yield after cyclization 59%, so pl. 195-197 ° C (from ethanol).
    Example 24. Obtaining 4-acetyl-3-amino-2-ethyl-5-methyl-pyrrole-hydrochloride.
    The title compound is obtained with a total yield of 73% from 2-amino-butyronuitrile and acetylacetone. T. pl. 245-24 Pc (from methanol). .
    Example 25. Obtaining 3-amino-4- (p-methoxybenzoyl) -5-methyl-2-phenyl-pyrrole.
    The title compound was prepared from 2-amino-2-phenyl-acetonitrile and (p-methoxybenzoyl) acetone in 43% yield, mp. 219-221 ° C (from ethanol).
    Example 26. Obtaining 4-acetyl-3-amino-2- (p-benzyloxyphenyl) -5-methyl-P11rrol.
    The named compound is obtained from 2-C1-MINO-2- (p-benzyloxyphenyl) acetonitrile and acetylacetone in 51% yield, mp, 245-250 0 (from ethanol).
    PRI-MER 27. By; teaching of 4-acetyl-3-amino-2- (p-chlorophenyl) -5-methyl-pyrrol.
    The title compound is obtained in 67% yield, starting from 2-amino-2- (p-chlorophenyl) -acetonitrile and acetylacetone. T. pl. 205-208 (of
    o ethanol).
    Example 28. Obtaining 3-amino-4-carbethoxy-2- (p-methoxyphenyl) -5-methyl-pyrrole.
    The title compound was prepared from 2-amino-2- (p-methoxyphenyl) -acetonitol 5-ethyl and ethyl acetate in 44% yield, m.p. 234-2360С.
    Example 29. Obtaining 3-amino-4-benzoyl-2- (p-fluorophenyl) -5-me0 til-pyrrole.
    Starting from 2-amino-2- (p-fluorophenyl) -acetonitrile and benzoyl acetone, a branched intermediate is obtained. T. Kip. 0.2 mm Hg After cyclization, the yield of the target product is 6.6%, so pl. 209-210s (from ethanol / diethyl ether).
    Example 30. Preparation of 4-acetyl-3-amino-2- (o-tolyl) -5-methyl-pyr0 roll.
    Starting from 2-amino-2- {o-tolyl) -acetonitrile and acetylacetone, a branched intermediate product is obtained, t. kip 120s / 0.2 mm Hg Output
    5 products after cyclization 77%, so pl. (from methanol).
    Example 31. Preparation of 3-amnno-4-carbomethoxy-5-carbomethoximtil-2-phenylpyrr-hydrochloride.
    0
    The title compound is obtained in 48% yield, starting from 2-amino-2-fe -. nyl-acetonitrile and 1,3-dicarbomethoxyacetone. M.p. 210-213Ос (from methanol).
    Example 32. Preparation of 3-am5 but-5-methyl-4-methylcarbamyl-2-phenium-pyrrole-hydrochloride.
    The title compound is obtained in 55% yield, starting from 2-amino-2-phenyl-acetonitrile and ct -acetyl-M-methyl-acetamide. T. pl. 247-250 C (from ethanol).
    Example 33. Preparation of 3-amino-4- (o-chlorobenzoyl) -5-methyl-2-phenyl-pyrrole.
    five
    The title compound is obtained with a total dosage of 51%, starting from 2-amino-2-phenyl-sshchetonitrile and o-chlorobenzoyl of Scarlet. T. pl. 214-2160С (from ethanol) .0
    Example 34. Preparation of 3-amine-4-carbamyl-5-methyl-2-phenyl-pyrrole-hydrochloride.
    Starting from 2-amino-2-phenyl-acetonitrile and ct-α-acetyl-acetylmide, a branched intermediate is obtained.
    compound. T. pl. 128-130С (from ethyl ether). After cyclization, the target product is obtained with a yield of 49%, so pl. 307-309 C (from methanol).
    Example 35: Preparation of 3-amino-4-butyryl-2-phenyl-5-propyl-pyrrole-hydrochloride.
    The title compound is obtained in a total yield of 60%, starting from 2-amino-2-phenyl-acetonitrile and nonan-4, 6-dione. T. pl. 228-230 0 with decomposition (from methanol / diethyl ether).
    Example 36. Preparation of 3-amino-4-butyryl-5-methyl-2-phenyl-pyrrole-hydrochloride.
    The title compound is obtained in 48% yield from 2-amino-2-phenyl-acetonitrile and heptane-2,4-dione. T. pl. 240-245 With decomposition (from methanol / diethyl ether).
    Example 37. Preparation of 3-amino-4, 5-dicarbomethoxy-2- (p-chlorophenyl) -py15rol hydrochloride.
    Starting from 2-amino-2- (p-chlorophenyl) -acetonitrile and dicarbomethoxyacetylene, an intermediate compound is obtained, melting point, 74-7b C (from diethyl ether).
    The yield of cyclized product 48% so pl. 216-218 ° C (from methanol / diethyl ether).
    I38 Example Preparation of 3-amino-4, 5-dicarbomethoxy-2- (p-tolyl) -pyrrole-hydrochloride.
    Starting from 2-amino-2- (p-tolyl) -acetonitrile and dicarbomethoxyacetylene, a branched intermediate is obtained, mp. 76-77 ° C (from diethyl ether / hexane). The total yield of cyclized product 70%, so pl. 193-19b C (from methanol / diethyl ether).
    Example 39. Preparation of 3-amino-4, 5-dicarbomethoxy-2-phenyl-pyrrole-hydrochloride.
    Starting from 2-amino-2-phenyl-acetonitrile and dicarbethoxyacetylene, a branched intermediate is obtained, b.p. 140s / 0.03 mm Hg Art. The total yield of the cyclized compound is 78%, m.p. 193196 0 (from ethanol / diethyl ether).
    Example 40. Preparation of 3-amino-4, 5-dicarbomethoxy-2- (p-methoxyphenyl) f-pyrrole hydrochloride.
    Starting from 2-amino-2- (p-methoxyphenium; |) -acetonitrile and dicarbomethoxyacetylene, a branched intermediate is obtained, mp. 8688 C (from hexane). The total yield of the cyclized compound is 63%, so pl. 195-197 ° C (from methanol / diethyl ether).
    Example 41. Preparation of 3-amino-4, 5-dicarbomethoxy-2-ethyl-pyrrole-hydrochloride.
    The title compound is obtained with a total yield of 66% from 2-amino-butyronitrile and dicarbomethoxyacetylene. T. pl. 209-210 C (from diethyl ether / methanol).
    Example .42. Preparation of 3-amino-4, 5-dicarbomethoxy-2-phenyl-pyrrole-hydrochloride.
    The title compound is obtained in 39% overall yield from 2-amino-2-phenyl-acetonitrile and dicarbomethoxyacetylene. T. pl. 205-207с (from methanol diethyl ether) .Т. square free base 142-143-C (from diethyl ether).
    Example 43 Preparation of 4-acetyl-3- (2-carbethoxyacetylamino) -5-methyl-2-phenyl-pyrrole.
    16 g (0.0748 mol of 4-acetyl-3-amino-5-methyl-2-phenyl-pyrrole hydrochloride of Example 1) is dissolved in 300 m of chloroform, a saturated solution of sodium bicarbonate is added and 14 g are added dropwise ( 0.0933 mol) of malonic acid ethyl ester chloride, the mixture is vigorously stirred for 2 hours at room temperature. The solution is evaporated to dryness, the residue is dissolved in diethyl ether and filtered. Upon recrystallization from acetone / hexane, 13.5 of the title compound are obtained with m.p. 178180SS.
    Example 44. Preparation of 4-carbethoxy-3- (2-carbethoxyacetylamino) -5-methyl-2-phenyl-pyrrole is carried out analogously to example 43. from the compound of example 2 and malonic acid ester chloride. Yield 86%. T. pl. 156-158 C (from acetone).
    Example 45. Preparation of 4-acetyl-3-benzoylaminr-5-methyl-2-phenyl-pyrrole is carried out analogously to example 43 from the compound of example 1 and benzoyl chloride. Yield 79%. T. pl. (from ethanol / water).
    The following 3-aminopyrrole derivatives are acetylated with acetic anhydride in the presence of pyridine in the usual manner.
    Example 46. 3-Acetylamino-4-carbethoxy-5-methyl-2-phenyl-pyrrole is obtained by acetylation of the compound of Example 2. 89% yield, m.p. 213215 With (from ethanol).
    Example 47. 3-Acetylamino-4-benzoyl-5-methyl-pyrrole is obtained from the compound of Example 11. The yield is 86%, so pl. 182-183 seconds (from ethyl acetate / water).
    Example 48. 4-Acetyl-3-acetyamino-5-methyl-pyrrole is obtained from the compound of Example 12. The yield is 72%, so pl. 206-2080С (from methanol).
    Example 49. 4-Acetyl-3-acetyamino-5-methyl-2-phenyl-pyrrole is prepared from the compound of example 1. Yield
    80%, mp. 215-2170С (from acetone / hexane).
    Example 50. Acetylamino-4-carbethoxy-5-methyl-pyrrole is obtained from the compound of Example 20, Yield 90% / m.p. IGS-lTO c (from ethyl acetate).
    Example 51. 4-Acetyl-3-6enzenesulfonamido-5-methyl-2-phenyl-pyrrole b (0.0332 mol) of the compound of Example 1 is suspended in 100 ml of aqueous 10% sodium hydroxide, then, by stirring, 20 ml (0,0154 mol) of benzenesulfonyl chloride at 5 ° C. The resulting oily residue is separated from the aqueous layer, dissolved in ethyl acetate and washed three times with aqueous 10% sodium hydroxide. The alkaline aqueous solutions are combined, the pH of the resulting solution is adjusted to 2.5 with aqueous 10% hydrochloric acid. The precipitate formed is filtered and recrystallized. It is isolated from aqueous ethanol with a yield of 6.7 g. M.p. 170-173 0.
    Example 52. Preparation of 4-acetyl-3-methanesulfonamyl-5-methyl-2-phenyl-pyrrole.
    To a solution of 5 g (0.0278 mol) of the compound of example 1 in 40 ml of pyridine, with stirring, 2.6 g (0.0228 mol) of methanesulfonyl chloride at OOC were added. Stirring is continued for 1 hour and the mixture is stirred overnight at, then poured into aqueous 1O% hydrochloric acid, the resulting precipitate is filtered and recrystallized. The aqueous is extracted from aqueous ethanol in a yield of 4.1 g. 172-175 C.
    Example 53. 4-Carbethoxy-3-methanesulfonamido-5-methyl-2-phenyl-pyrrole was prepared as in Example 52 from the compound of Example 2 and methanesulfonyl chloride in 83% yield. M.p. 173-174 ° C (from aqueous ethanol),
    Example 54: 4,5-Dicarbomethoxy-3-methanesulfonamido-2-phenyl-pyrrole is prepared as in Example 52 from the compound of Example 42 and methane sulfonyl chloride in 77% yield. Mp, 158-1 ° C (from aqueous ethanol).
    Example 55. 4-Acetyl-5-methyl-3-phenacylsulfonamido-2-phenyl-pyrrole is prepared analogously to example 52 from the compound of example 1 phenacylsulfonyl chloride in 89% yield, y. square 201-20 ° C (from acetone / hexane).
    Example 56 4-Benzoyl-5-methyl-2-phenyl-3- (p-toluenesulfonamido) -pyrrole was prepared as in Example 52 from the compound of Example 3 and p-toluenesulfonyl chloride in 83% yield. T. pl, 230-2330С (from ethanol / water).
    Example 57 Preparation of 4-acetyl-5-methyl-3- (N-methylphenacylsulfonamide) -2t-phenyl-pyrrole.
    A mixture of 5.0 g (0.0126 mol) of the compound of Example 55; 5.0 g of potassium carbonate and 15 ml (0.159 mol) of dimethyl sulfate in 400 ml of acetone are heated under reflux for 35 hours. The reaction mixture is concentrated to a small volume, 400 ml of water are added, the precipitated precipitate is filtered and recrystallized from hexane in 4, 5 g. T. pl. 195197 S.
    0
    In the same manner as in Example 57, alkylation is carried out and the following compounds are prepared.
    Example 58. 4-Acetio-5-methyl-3- (N-methylbenzenesulfonamide) 5 -2-phenyl-pyrrole is obtained from the compound of Example 51 and dimethyl sulfate in 72% yield. T. pl, 247-249 0 (from acetone / water).
    Example 59. 4-Acetyl-3-dimethylammono-5-methyl-2-phenyl-pyrrole
    0 is prepared from the compound of example 1 and dimethyl sulfate in 65% yield. T, pl. 153-155 C (from chloroform),
    Example 60. 4-Benzoyl-3- (N-ethyl-p-tolysulfonamido) -55-methyl-2-phenyl-pyrrole is prepared from the compound of example 56 and diethyl sulfate in 67% yield. T. pl. 224-225 C (from ethanol).
    EXAMPLE 61. Preparation of 4-ben-zoyl-3-isoprpylamino-5-methyl-2-phenyl-pyrrole.
    The title compound was prepared by reacting equimolar amounts of the compound of Example 3 with iso5 propyl bromide at room temperature. Yield 31%, so pl. 132-136 C (from hexane).
    Example 62. Preparation of 4,5-dicarbomethoxy-2-phenyl-3-ureido-0-pyrrole.
    To a solution (5 g) of the compound of Example 42 in 50 ml of acetic acid, while stirring at room temperature, a solution of (13. g) sodium cyanate in 20 ml of water is added. The reaction mass is kept for about 1 hour. The crystallizing product is filtered and recrystallized from methanol with a yield of 5.1 g. So pl. 246-248 0.
    0
    According to the method of Example 62, the following compounds were prepared.
    Example 63. 4-Acetyl-5-methyl-2-phenyl-3-ureido-pyrrole is obtained from the compound of example 1 and sodium cyanate and sodium in a yield of 82%. m.p. 234-238 ° C (from acetone / hexane),
    Example 64. 4-Carbethoxy-5-methyl-2-phenyl-3-ureido-pyrrole is prepared from the compound of Example 2 and sodium cyano with a yield of 66%. T. pl. 217-219s (from ethanol),
    Example 65. 4-Carbethoxy-: 5-methyl-2-phenyl-3- (3-phenylureido) -pyrrole is prepared from the compound of example 2 and the phenyl isocyanate to yield
    five
    70%. T. pl. 224-22 BOC (from methanol / water).
    Example 66. 4-Acetyl-5-methyl-2-phenyl-3- (3-phenylureido) -pyrrol is obtained from the compound of example 1 and phenyl isocyanate in 62% yield. T. pl. 256-257®C (from acetone).
    Example 67. 4-Acetyl-3- (3-benzoylthioureido) -5-methyl-2-phenyl-pyrrole is obtained from the compound of Example 1 and the benzoylisothiocyanate in 69% yield, mp. 228-230s (from ethan / water).
    Example 68 Preparation of 4-acetyl-3-formamido-2- (p-methoxyphenyl) -5-methyl-pyrrole.
    5 g (0.0206 mol) of the compound in Example 15 are dissolved in 50 ml of 85% formic acid, the resulting solution is heated under reflux for 15-20 minutes. Then the reaction mixture is cooled and poured into ice water. The precipitate is filtered and recrystallized from methanol with a yield of 2.5. T. pl. 210-211 C.
    Example 69. 4-Carbethoxy-3-formamido-5-methyl-2-phenyl-pyrrole is prepared as in Example 68, starting from the compound of Example 2. Yield 83%. T. pl. 180-182C with (from ethanol / water).
    Example 70. Preparation of 4-acetyl-3- (p-chlorobenzylideneamino) -5-methyl-2-phenyl-pyrrole.
    A solution of 5.0 g (0.0234 mol) of the compound of Example 1 in 200 ml of ethanol was added to a solution of 5.0 g (0.0358 mol) of p-chlorobenzaldehyde in 100 ml of ethanol at 45-500 s, then the resulting mixture was heated to reverse fridge about 4h. After cooling, the reaction mixture is poured into 1200 ml of water saturated with sodium chloride. The precipitate is filtered and recrystallized from ethanol / water. Exit 9.5 g. T. pl. 214215 C.
    Example 71. 4-Acetyl-3-benzylideneamino-5-methyl-2-phenyl-pyrrole was prepared as in Example 70 from the compound of Example 1 and benzaldehyde. 87%. T. pl. 173-176 ° C (from methanol).
    Pmeper 72. 4-Carbamyl-3-isopropylLidenamino-5-methyl-2-phenyl-pyrrole is prepared in the same manner as in Example 70 of the following 11 compounds of Example 34 and acetone in 82% yield. T. pl. 221-223 ° C tH3 4-tanol / hexane). -.,
    Example 73, 3-Benzylideneamino-4, 5-dicarbomethoxy-2-phenyl-pyrrole, was prepared as in Example 70 from the compound of Example 42 and benzaldehyde in 78% yield. m.p. 218220 0 (from methanol).
    Example 74. Preparation of 4-ats. Tetyl-3-amino-1, 5-dimethyl-2-phenyl-pyrrole,.
    a) A solution of 1.4 g (0.00467 mol) of the compound of Example 71 in 25 ml of dimethylformamide was added dropwise to a cold suspension of sodium hydride in 10 ml of dimethylformamide. The resulting mixture was washed 15 times at 0-5CC, then 1 ml of methyl iodide (0.0161 mol) was added. Stirring is continued for 30 minutes at and 30 minutes at room temperature, then 150 ml of water is added and then the reaction mixture is extracted with diethyl ether. The organic phase is separated, the solvent is distilled off. The resulting residue (1.2 g) is recrystallized from isopropanol / water. T. pl. 136-138C. The product is 4-acetyl-3-benzylideneamino-1; 5-dimethyl-2-phenyl-pyrrole.
    b) 1.0 g (0.00316 mol) of the compound obtained in paragraph a is dissolved in 30 ml of 10% hydrochloric acid, the resulting solution is heated at 80-90 0 for about 2 hours. Upon cooling and neutralization with sodium hydroxide, a precipitate forms which is recrystallized from ethanol / water to yield 0.8t of the title compound. .T. square 124-12b S.T. pl. the corresponding hydrochloride 208-209 from ethanol / diethyl ether).
    Example 75. Preparation of 4-acetyl-3-amino-1-ethyl-5-methyl-2-phenyl-pyrrole.
    Similarly to point 74 of Example 74 and starting from the compound of Example 71 and ethyl iodide, 4-acetyl-3-benzylidene-amino-1-ethyl-5-methyl-2-phenyl-pyrrole is obtained. T .. pl. 139-141 (from isopropanol / water),
    This compound is hydrolyzed in a manner similar to paragraph b of Example 74. The total yield of the obtained compound is 54%. T. pl. 107-108 C (from ethanol).
    . Example 76. Preparation of 4-acyl-3-amino-5-phenyl-1-propyl-pyrrole.
    Using propylene iodide as the starting material of Example 71, proceeds as described in Example 74, and 4-acetyl-3-benzylideneamino-5-methyl-2-phenyl-1-propyl-pyrrole is obtained as an oil. This compound is hydrolyzed in a manner similar to paragraph b of Example 74. The yield of the obtained compound is 50%. T. pl. 113-115 0 (from ethanol).
    Example 77 Preparation of 4-acetyl-3-amino-1- (p-chlorobenzyl) -5-methyl-2-phenyl-pyrrole.
    4-Acetyl-3-benzylideneamino-1- (p-chlorobenzyl) -5-methyl-2-phenyl-pyrrole is obtained from the compound of example 71, and p-chlorobenzyl chloride, proceeding as in point 74 of example 74. So pl. 136-137 ° C (from ethanol / water). This compound is hydrolyzed in a manner similar to paragraph b of Example 74. The yield of the obtained compound is 58%. T. pl. 1616b C (from ethanol / water).
    Example 78. Preparation of 4-acetyl-1- (o-chlorobeneyl) -5-methyl-3-dimethyl-1-amino-2-phenyl-pyrrole is carried out by using the substance of example 59 and o-chlorobenzyl chloride as the starting compound and proceeding analogously to paragraph a Example 74. The yield of the obtained product is 67%. T. pl. 103-1050С (from isopropanol).
    Example 79. The preparation of 4-acyl - (p-chlorobenzyl) -5-methyl-3-dimethylamino-2-phenyl-pyrrole is carried out by using the compound of example 59 as the starting compound and p-chlorobenzyl chloride and acting as in Example 74. The yield of the obtained product is 52%. T. pl. 118-119s (from hexane).
    Example 80. Preparation of 4-cartoxy-3- (N-methyl-methanesulfonamido-1, 5-dimethyl-2-phenyl-pyrrole) is carried out starting from the compound of example 53 and methyl iodide and proceeding in the same way as in Example 74. The yield of the resulting product 71 ,%, Mp 138-140 ° C (from ethanol / acetone).
    Example 81. Preparation of 4-acyl-3- (o-carboxyphenyl) -amino-5-methyl-2-phenyl-pyrrole.
    A suspension of 2 g (0.00934 mol) of the compound of Example 1, 1.87 g (00934 mol of o-bromobenzoic acid, 2 g of sodium acetate and 0.5 g of powdered copper in 150 ml of water is heated under reflux for 4 hours. After cooling, the mixture incubated overnight. A precipitate is formed, it is filtered and recrystallized from aqueous methanol. The yield of the title product is 105 g.P.
    Example 82: Preparation of 3-amino-5-carbamyl-4-carbomethoxy-2-phenyl-pyrrole.
    A solution of 5 g (0.0161 mol) of the compound of Example 42 is saturated with ammonia, allowed to stand for 2 days, and the precipitated precipitate is filtered. Exit 2.8 g. T. pl. 177179 C (from methanol / water).
    Take p83. Preparation of 3-amino-4, 5-dicarboxy-2-phenyl-pyrrole. To a solution of 15 g (0.0545 mol) of the compound of Example 42 in 200 ml of methanol was added 90 ml of aqueous 10% lithium hydroxide and heated under reflux for 20 minutes while stirring. The solution is then poured into water, the mixture is acidified with aqueous 10% hydrochloric acid. The precipitate formed is filtered and recrystallized from dimethylformamide / ethyl ether. Exit 12.5 g. T. pl. 191-194 C (the compound contains one molecule of water of crystallization).
    Example 84. Preparation of 3-amino-5-carboxy-4-carbomethoxy-2-phenyl-pyrrole.
    A solution of 10 g (0.0322 mol) of the compound of Example 42 in 150 ml of methanol and 30 ml of aqueous 10% sodium hydroxide is heated under reflux for 3 hours. The methanol is distilled off, the pH of the resulting solution is adjusted to 7 with hydrochloric acid. The precipitate is filtered,
    dissolved in aqueous sodium bicarbonate and then neutralized with 10% hydrochloric acid. Exit 5 g. T. pl. 206-2070С.
    Example 85. Preparation of 3-am5 of but-4-carboxy-5-Xbfomethoxy-2-phenyl-pyrrole 2 g (0.00644 mol) of the compound of example 42 are dissolved in 20 ml of concentrated true acid, the solution is kept at room temperature for about 35 minutes The mixture is then poured into ice water, and the mixture is neutralized with aqueous 10% sodium hydroxide. The precipitated precipitate 5 is filtered and recrystallized from aqueous methanol. Yield 0.5 g. T. pl. 218-219 ° C.
    In accordance with the hydrolysis described in Example 85, a barely - is obtained. Q blowing.
    Example 86. 4-Carboxy-3- (2-carbethoxy-acetylamino-5-methyl-2-phenyl-pyrrole is obtained in 64% yield, starting from the compound of Example 44. P. mp 92-98 0 (from ethanol).
    five
    Example 87: 3-Acetylamino-4-carboxy-5-methyl-2-phenyl-pyrrole is obtained in 49% yield, starting from the compound of Example 46. M.P. 258260 C (from ethanol / water). 0 Example 88. 4-Carboxy-3-methanesulfonamido-5-methyl-2-phenyl-pyrrole is obtained in 54% yield, starting from the compound of Example 53, mp. 269-271 ° C (from acetone / water). 5 Example 89. Preparation of 3-amino-5-carbazoyl-4-carbomethoxy-2-phenyl-pyrrole.
    5 g (0.0161 mol) of the compound of Example 42 was dissolved in 60 ml of methanol, 1.3 g of pyridine was added and 25 ml of hydrazine was poured into 20 ml of water. The mixture is kept for 15 minutes at room temperature. The crystallized product is isolated by filtration and recrystallized from methanol. Exit 3 g. T. pl. 166-167 ° C.
    Example 90. Preparation of 4-acetyl-3-amino-5-methyl-2- (p-hydroxyphenyl) -pyrrole is carried out starting from the compound of example 15 and similarly to the known method for the hydrolysis of o-alkylphenols. Yield 71%. T. pl. 273274 C (from ethanol / water),
    Example 91. Preparation of 3-amino-5-methyl-2-phenyl-4-phenylcarbamyl-5-pyrrole is carried out similarly to that described for Examples 1-42, starting from 2-amino-phenyl-acetonitrile and 2-acetyl-M-fe -acetamide. Total yield 73%. M.p. 271-273С (from ethanol).
    Example 92: Preparation of 3-amino-4, 5-dicarbomethoxy-2-phenyl-pyrrole-hydrochloride.
    9.0 g of potassium carbonate was added to a solution of 9.5 g (0.0565 mol) of 2-amino-2-phenyl-acetonitrile hydrochloride in 90 ml of anhydrous methanol, stirring the mixture for 15 minutes and adding 8.0 g (O , 063 O mol) 1,2-dicarbomethoxyacetylene. The reaction mass is heated under reflux for 3.5 hours, the solvent is distilled off, the residue is dissolved in ethyl acetate and washed three times with 10% hydrochloric acid. The resulting hydrochloric acid solution is neutralized with 10% sodium hydroxide and extracted again with ethyl acetate. After removing the solvent, a solid is obtained which is recrystallized from a mixture of methanol and diethyl ether saturated with hydrogen chloride. The yield of the title compound 5 g. T. pl. 205-20700. T. pl. 142-143 seconds of free base (from diethyl ether).
    Example 93. Preparation of 4-acetyl-5-methyl-3-methylamino-2-phenyl-pyrrole.
    1.5 g (0.0036 mol) of the compound of Example 57 are suspended in 5 ml of acetic acid and 5 ml of concentrated hydrochloric acid, then zinc powder is added in small portions. The reaction mixture is stirred at room temperature for 2 hours, the zinc is filtered off and the filtrate is extracted twice with 200 ml of ethyl acetate. After distilling off the solvent, the precipitate is treated with ether and filtered. Yield 0.3 g. T. pl. 174-17 bOs . EXAMPLE 94. 4-Benzoyl-3-ethylamine 6-5-methyl-2-phenyl-pyrrole is prepared from the compound of Example 60 as described in Example 93. The yield of the obtained compound is 44%. T. pl. 178-1800s (from ethanol / water).
    Example 95. 3-Acetylamino-4-benzoyl-5-methyl-2-phenyl-pyrrole is prepared in a manner similar to Method 43 from the compound of Example 3 and acetyl chloride. Exit 87%. T. pl. 140-142 ° C (from ethanol and // into odes).
    权利要求:
    Claims (1)
    [1]
    i. Claim method for preparing aminopyrrole derivatives of general formula (I)
    ..LL
    i W
    or its salts with pharmaceutically acceptable acids,
    . where R is hydrogen, (C) -alkyl, benzyl or benzyl substituted by chlorine atom;
    5 R is hydrogen, (C ,.) -alkyl, unsubstituted or substituted by a halogen atom, methyl or methoxy phenyl
    QH is hydrogen, (C) is alkyl, formyl, (h-) aliphatic acyl, benzoyl, carboethoxycyl acetyl, carbamyl, phenylcarbamyl, thiocarbamyl, phenylthiocarbamyl, benzoylthiocarbamyl, carboxyphenyl, benzenesulfonyl, methylsulfonyl / cycloxyphenyl, and R is hydrogen or (s.) -Alkyl;
    R - (Cr.i) is an aliphatic acyl, benzoyl, substituted by a chlorine atom or a methoxy group, benzoyl, carbo- () -alkoxy, carboxy, carbamyl, methylcarbamyl or phenylcarbamyl;
    Rp is hydrogen, () -alkyl, carbo- () -alkoxy, carboethoxymethyl, trifluoromethyl, carboxy, carbamyl, or carbazoyl; I R- and Rn - together - (Cg,) - al; kiliden, benzylidene
    or substituted by atom
    benzylidene chlorine; R and R- - together - the group -CO-CHi -CHj -CHj-, where
    the carbonyl part is bonded to the carbon atom of the pyrrole ring containing the substituent RA, an is an integer equal to 2, 3 or 4 with R,, j and RH; one of the radicals R, or RI must not be hydrogen, and R / must not to be a carboq ethoxy group, characterized in that equimolar amounts of ot-aminonitrile of the general formula (II)
    :. -l :: .-. / “V (in
    5 V
      - In - or its acid additive salt,
    where R is H and R has the above values, reacts with a compound of general formula (III)
    RA
    . X (III)
     "5 where R and Rg have the above
    5 values, and X means -C5C groups
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    同族专利:
    公开号 | 公开日
    NO742862L|1975-03-24|
    ES429446A1|1977-02-16|
    CH605741A5|1978-10-13|
    YU214174A|1982-06-18|
    CA1050556A|1979-03-13|
    BE819088A|1974-12-16|
    JPS5328914B2|1978-08-17|
    NO143845C|1981-04-22|
    SE394429B|1977-06-27|
    RO70534A|1981-07-30|
    RO70535A|1981-08-17|
    CS188201B2|1979-02-28|
    FI61879B|1982-06-30|
    FR2241308B1|1977-09-09|
    DE2439284C2|1982-07-29|
    AU7221074A|1976-02-12|
    DE2462963C2|1982-12-02|
    ATA684774A|1976-09-15|
    AR210246A1|1977-07-15|
    AR210133A1|1977-06-30|
    DK156391C|1990-01-08|
    YU36926B|1984-08-31|
    RO72882A|1987-02-27|
    DK445974A|1975-04-28|
    DE2462967C2|1982-12-02|
    FI61879C|1982-10-11|
    DK156391B|1989-08-14|
    PL95235B1|1977-09-30|
    IN140329B|1976-10-16|
    NL7411092A|1975-02-25|
    ZA744754B|1975-08-27|
    IE40290B1|1979-04-25|
    IE40290L|1975-02-22|
    DE2439284A1|1975-03-06|
    GB1427945A|1976-03-10|
    HU169728B|1977-02-28|
    ES449425A1|1977-07-01|
    PL96806B1|1978-01-31|
    AR210132A1|1977-06-30|
    ES449426A1|1977-07-01|
    NO143845B|1981-01-12|
    IL45368D0|1974-10-22|
    DE2462966C2|1983-12-29|
    FI246274A|1975-02-23|
    JPS5070356A|1975-06-11|
    DD113756A5|1975-06-20|
    SE7410636L|1975-02-24|
    IL45368A|1977-10-31|
    FR2241308A1|1975-03-21|
    AT336600B|1977-05-10|
    RO72882B|1987-02-28|
    LU70764A1|1975-01-02|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    GB1148908A|1965-04-19|1969-04-16|Sumitomo Chemical Co|Indole derivatives and processes for making them|
    GB1187903A|1967-09-29|1970-04-15|Sumitomo Chemical Co|Glucuronides of 3-Indolylaliphatic Acid Derivatives and Processes for Producing them|GB1492663A|1975-02-20|1977-11-23|Lepetit Spa|4-amino-3-pyrrole carboxamides|
    GB1548398A|1975-06-05|1979-07-11|Lilly Industries Ltd|Acylamino pyrroles furans and thiophenes|
    DE3212591A1|1982-04-03|1983-10-13|Gödecke AG, 1000 Berlin|2-PYRROLIN-3-CARBONITRIL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THE SAME|
    JPH0216740U|1988-07-21|1990-02-02|
    EP0390739B1|1989-03-28|1995-08-09|Ciba-Geigy Ag|Substituted aminopyrroles as stabilisers in chlorinated polymers|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB3979073A|GB1427945A|1973-08-22|1973-08-22|Aminopyrrole derivatives|
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