• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    1535967 Anti - lipidemic pharmaceutical compositions containing amino-benzoic acid derivatives AMERICAN CYANAMID CO 16 Feb 1976 [12 March 1975] 06047/76 Heading A5B [Also in Division C2] Pharmaceutical compositions comprise a compound of formula I: wherein R 1 is selected from hydrogen, (C 1 -C 6 ) alkyl, benzyl, di(C 1 -C 6 ) alkylaminoethyl and (C 1 -C 6 ) alkoxyethyl; R 2 is selected from aryl and substituted aryl wherein the substituents are selected from halo, alkyl, alkoxy and benzyloxy, A is selected from C n H 2n , wherein n=1-16 and C n H 2n-2 wherein n=3-16; or a pharmaceutically acceptable salt thereof; in conjunction with a pharmaceutically acceptable carrier or diluent excluding in the compositions containing p - [(3-phenylpropyl) amino] benzoic acid; p-benzylaminobenzoic acid; ethyl-p-benzylaminobenzoate; p-[(p - methoxybenzyl) amino] benzoic acid; ethyl-p-(#-phenethylamino) benzoate; p-(#-phenethylamino) benzoic acid; and p-[#-(3, 4-dimethoxyphenyl) ethylamino] benzoic acid wherein the carrier or diluent is non sterile water or a non sterile simple organic solvent. The compositions have use in treatment of hyperlipidemia.
    公开号:SU803856A3
    申请号:SU762332503
    申请日:1976-03-12
    公开日:1981-02-07
    发明作者:Дональд Олбраит Джеи；Гари Маинер Томас；Гордон Шеферд Роберт
    申请人:Американ Цианамид Компани (Фирма)；
    IPC主号:
    专利说明:

    powder or sodium iodide, when arylalkyl or arylalkenyl halides are used as alkylating agents.
    Example 1, and- (Phenethylamino) benzoic acid.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 10.3 g of (2-bromoethyl) benzene and 50 ml of hexamethylphosphoramide heating IIOT on oil at 115-120 0 for 17 h.
    The mixture was poured into ice water and extracted with ether. The ether extracts are washed with water, dried over magnesium sulphate and concentrated in vacuo to an oily product. The resulting oil is mixed with 200 ml of ethanol-water solution (9: 1) and 20 g of potassium hydroxide and the mixture is heated under reflux for 3.5 hours. After cooling, the mixture is acidified with concentrated hydrochloric acid, diluted with 150 ml of water Cool, dilute with water and extract with chloroform. The chloroform extracts are washed with water, dried over magnesium sulfate, and concentrated in vacuo to form a sticky substance. Ethanol was added, the mixture was cooled, filtered, and yellow crystals were obtained. The mother liquor is cooled to -20 ° C and one more portion of crisps is obtained. Recrystallization of two portions of the obtained crystals from a mixture of hexane-ethanol gives yellow crystals, mp. 123-125 ° C. Recrystallization from ethanol yields pale yellow crystals; mp. 124-12bs.
    Example 2. p- (Decyloxy) -benzyl alcohol.
    To 100 ml of a 1.0 M solution of borohydride in tetrahydrofuran, cooled in an ice bath, 27.8 g of p-decyloxybenzoic acid in 300 m of tetrahydrofuran are added dropwise under a nitrogen atmosphere over 45 minutes. The mixture is stirred at room temperature for 6 hours and poured onto ice, diluted with water and 10 ml of concentrated hydrochloric acid. The mixture is filtered, the solid is sold with water and white crystals are obtained. Recrystallization from ethanol gives white plates, mp. 57.5-59c.
    PROMER 3, o Methanesulfonate p - Whereyloxy j-benzyl alcohol Ery.
    A mixture of 15.9 g of p- (decyloxy) benzyl alcohol (obtained by s according to the procedure of Example 2) and 9.1 ml of triethylamine in 300 ml of dichloromethane is cooled to -15 ° C in an iced bath. To the solution is added dropwise. 5.1 ml methanesulfonyl chloride B 5 ml dichloromethane for 10 min. stirred at -15 s for 30 min and drifted for 1Q min. The resulting mixture was washed with 100 ml of ice water, 100 ml of cold 10% hydrochloric acid, 100 ml of cold saturated sodium bicarbonate solution, 100 ml of cold saturated sodium chloride solution. The organic layer was dried over magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in dichloromethane and extracted with saturated sodium bicarbonate solution. Organic layer
    0 is dried over magnesium sulphate and concentrated in vacuo to give an oily product of a pale yellow color.
    Example 4. (Decyloxy5 benzyl) -amino-benzoic acid.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 15.6 g of p- (decyloxy) benzyl alcohol O-methanesulfonate {obtained according to the procedure of example 3) and 50 ml of hexamethylphosphorus amide are heated at 120 ° C for 22 hours. Solution cooled, diluted with 10 ml of water and 50 ml of ethanol and cooled again. Filtration gives a solid which is washed.
    5 50 ml of ethanol and water. The second portion of the substance is obtained from the filtrate. Two portions of the adhesive are heated with ethanol and the solvent is decanted until 200 ml of extractivate is obtained (some insoluble oily substance remains). Ethanol extracts are cooled, filtered, the solid is washed with ethanol and get
    5 crystals of reddish-brown color. Recrystallization from ethanol gives an off-white crystalline substance.
    The resulting material was combined with 50 ml of ethanol, 10 ml of water and 6 g of potassium hydroxide and the mixture was heated under reflux for 4 hours, then diluted with water and cooled. Filtration gives a solid, which is washed with water, dried, washed with benzene (50 ml) and crystals are obtained, m.p. 130-135 C and 158-160 C. Recrystallization from ethanol and from acetone gives white crystals, mp. 131-134 and 159-161 ° C.
    0
    Example 5. Ethyl-p- (4-biphenylmethyl) aminoZ-benzoate and p- (4-biphenylmethyl) amino benzoic acid.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 10.1 g of 4-chloromethylbiphenyl and 50 g of hexamethylphosphoramide is heated at 120 ° C for 22 hours. The mixture is cooled, diluted with 18 ml of water, cooled again and filtered. The solid is washed with water, ethanol and get reddish-brown crystals. Recrystallization from a mixture of 300 ml of ethanol and 75 ml of benzene gives reddish-brown crystals, mp.
    165-168 ° C, and from acetone - crystals of reddish-brown color, so pl. 164-167 ° C.
    A mixture of 5 g of the above ethyl ester, 5 g of potassium hydroxide, and 100 ml of ethanol-water (9: 1) was heated under reflux for 3 hours. The mixture was acidified with concentrated hydrochloric acid, diluted with 25 ml of water, cooled , filtered and receive pale yellow chips; taly, mp, 231-2Z5s. Recrystallization (lysis from ethanol-benzene to give yellow crystals, mp 234-23.7 ° C.
    Example 6. 11-Phenyl-1-undecanol.
    To 200 ml of a 1 m solution of borane in tetrahydrofuran cooled in an ice bath, a solution of 52.5 g of phenylundecanoic acid in 150 ml of tetrahydrofuran is added dropwise under nitrogen atmosphere over 35 minutes. The solution is left at room temperature for 5.5 hours; after what poured on the ice. To the mixture was added 8 ml of concentrated hydrochloric. acids and the mixture is diluted with water to 2.2 l. The mixture is extracted with ether (ca. 500 ml) and the extracts are dried over magnesium sulfate. Concentration in vacuo gives a colorless oil.
    P.P. and mep. 7. 11-Phenyl-1-undecanol-0-methanesulfonate.
    To a mixture of 750 ml of dichloromethane, 37, 2 g of 11-f-enyl-1-undec {-: ol (prepared in accordance with the procedure of example 6) and 32 ml of triethanolamine cooled in a salt-ice bath before 13-, 2 ml of methanesulfonyl chloride are added dropwise over 15 minutes. The mixture is cooled at (-10) (-15) ° C for 30 minutes and then washed with 300 ml of cold water, 300 ml of cold 10% hydrochloric acid, 300 ml of cold 5% sodium carbonate solution and 200 ml of cold saturated sodium chloride solution. The organic layer is dried over magnesium sulfate, concentrated in vacuo, and a pale yellow oil is obtained.
    Example 8.P- (11-Phenylundecyl) amino benzoic acid.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 16.3 g of 11-phenylundecanol-O-methanesulfonate (prepared as described in Example 7) and 50 ml of hexamethylphosphoramide are heated in an oil bath at 120 ° C for 20 hours. The mixture is poured into water with ice and extracted with chloroform. The extracts are washed with water 0.1 n. NaOH solution, saturated sodium chloride solution and water. After drying over magnesium sulfate, the extract is filtered through silica gel and the latter is washed with chloroform. The filtrate was concentrated in vacuo to an oil, which was mixed with 200 ml of an ethanol-water mixture (9: 1), 15 g of potassium hydroxide, and the mixture was heated under reflux for 3.5 hours, then acidified with concentrated hydrochloric. The acid is diluted with 50 ml of water and cooled. Dilution with 100 ml of ethanol and 25 ml of water, followed by filtration, gives a sticky substance that is washed with water. Remainder
    .. is dissolved in a mixture of hexane-ethyl acetate-acetic acid (40: 5: 5: 2) and; filtered through silica gel. The latter is washed with the same solvent (2 fractions). The first fraction is concentrated in vacuo to form a mash, which is recrystallized from hexane to give pale yellow crystals, m.p. 50-52C. Recrystallization from ether-hexane (1: 1). gives white crystals, so pl. 5530 55 C.
    Example 9. Ethyl p-benzylaminobenzoate.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 8.55 g of benzyl bromide and 45 ml
    5 hexamethylphosphoramide is heated in an oil bath for 20 hours. The mixture is diluted with water, cooled, filtered,. and the solid is washed with water to obtain
    -. reddish brown crystals,
    m.p. 90-93 ° C. The sample is recrystallized from ethanol to obtain
    crystals of reddish-brown color, so pl. 96-97 ° C.
    Example 10. p-Benzylaminobenzoic acid.
    A mixture of 6.0 g of ethyl p-benzylaminobenzoate (prepared according to the procedure of Example 9), 100 ml of ethanol-water (9: 1) and 6.0 g of potassium hydroxide are refluxed.
    3.5 hours. The mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled, filtered, and the solid washed with water. Pale cream crystals are obtained.
    colors, so pl. , 165-168с. Recrystallization from ethanol gives reddish-brown crystals, m.p. 167-1b9 ° C. Example 1. It.il-p-p- (benzyloxy) benzylamino} -benzoate.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 11.64 g of p-benzyloxybenzyl chloride and 50 ml of hexamethylphosphoramide is heated in an oil bath for 20 hours. The mixture is cooled, diluted with 25 ml of water, cooled again and the resulting solid the mass is diluted with an additional portion of water to allow filtration. Solid residue
    washed with water, recrystallized from ethanol and get crystals, not quite white, so pl. 144-146 C. The sample is recrystallized from ethanol to give crystals, mp. 146-147 ° C.
    Example 12. (Benzyloxy) benylamino-benzoic acid.
    A mixture of 10 g of ethyl p-p- (benzyloxy) benzylamino-benzoate (prepared according to the procedure of Example 11), 10 g of potassium hydroxide and 200 ml of a mixture of ethanol and water (9: 1) are refluxed for 4.5 The mixture was acidified with concentrated salt of HOiTt acid during heating. As a result of dilutions with water and filtration, reddish-brown crystals are obtained, which are recrystallized from glacial acetic acid to give off-white crystals, mp. 206-208С.
    Example 13. (Phenylhexyl) amino benzoic acid.
    A solution of 8.13 g of ethyl p GB- (phenyl hexyl) amino benzoate and 2.81 g of potassium hydroxide in 90 ml of 95% ethanol is heated and heated under reflux for 5 hours. To the hot reaction mixture 5 ml of concentrated hydrochloric acid is added. The mixture is cooled to room temperature, 100 ml of water is added and it is cooled again. The first product is collected, filtered, washed with water, dried, and then recrystallized from absolute alcohol to give tan crystals, t. Pl. 126-129 ° C.
    Example 14. Ethyl p- (p-methoxybenzyl) amino benzoate.
    A mixture of 33 g of ethyl p-aminobenzoate, 100 ml of hexamethylphosphoramide and 15.7 g of p- (chloromethyl) anisole is heated at 100-110 ° C for 22 hours. The solution is cooled, diluted with 60 ml of water, cooled again, filtered, the solid obtained is washed with ethanol and water and yellow crystals are obtained. Recrystallization from ethanol yields pale yellow crystals; mp. 128-130 ° C.
    Example 15. p- (p-Methoxybenzyl) amino-benzoic acid.
    A mixture of 15 g of ethyl p-tsetoxybenzyl amino benzoate (prepared according to the procedure of Example 14), 15 g of potassium hydroxide and 200 ml of a mixture of ethanol and water (9: 1) are refluxed for 3 hours, acidified the hot solution is concentrated hydrochloric acid, diluted with water, cooled, filtered, the solid is washed with water, and tan crystals are obtained. 208-210s. Recrystallization from ethanol is obtained. not quite white crystals, so pl. 209210 ° C ..
    Example 16. p- (Benzyloxy) phenethanol.
    To 120 ml of a 1.0 M solution of borane in tetrahydrofuran, cooled in an ice bath, 14.5 g of (p-benzyloxyphenyl) acetic acid in 100 ml of dry tetrahydrofuran are added dropwise over 25 minutes. After 17 hours at room temperature, the mixture is poured onto ice. After the ice has melted, it is filtered to obtain white crystals, m.p. 7275 ° C.
    Example 17. p- (BenzylCi) phenethanol-0-methanesulfonate.
    o
    To a mixture of 250 ml of dichloroethane, 11.42 g of p- (benzyloxy) -phenethanol (obtained in accordance with the procedure of example 16) and 10.7 ml of triethylamine, cooled to -10 ° C, are added dropwise within 10 minutes . 6.23 g (4.21 ml) of methanesulfonyl chloride in 10 ml of dichloromethane. After 45 min, the mixture is washed with 100 ml of ice water, 100 ml of 10% hydrochloric solution.
    Acidic acid, 100 ml of cold saturated sodium bicarbonate solution, 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solvent removed in vacuo. The oil crystallizes and gives white.
    5 crystals, so pl. 62-65 ° C.
    Example 18. Ethyl p- (p-benzyloxyphenethyl) amino benzoate.
    A mixture of 16.5 g of ethyl p-aminobenzoate, 15.3 g of p- (benzyloxy) phenethanol D 0-methanesulfonate (prepared as described in Example 17), and 50 ml of hexamethylphosphoramide are heated in an oil bath at 110 ° C for 20 h. The solution is cooled, diluted with 30 W
    5 water, 10 ml of ethanol, cool again, filter, and the solid is washed with an aqueous solution of ethanol and water. The solid obtained is recrystallized (twice) from ethanol and market-brown crystals are obtained, mp. 94-97c. Recrystallization from ethanol gives reddish-brown crystals, so pl. 95-97C.
    Example 19. p-1 (p-Benziloc5 siphenetil) amino-benzoic acid.
    A mixture of 6.0 g of ethyl-p- (p-benzyloxyphenethyl) amino-benzoate (prepared according to the procedure of example 18), 6.0 g of potassium hydroxide and
    0 100 ml of an ethanol-water mixture (9: 1) are refluxed for 3.5 hours. The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, filtered, the solid is washed with water and reddish-brown crystals are obtained. t. pl. 180-185 C. Recrystallization-. It from the glacial acetic acid get reddish-brown crystals, so pl. 187-189 ° C.
    0
    Example 20. p- (Tridecyloxy) benzyl alcohol.
    To 200 ml of a 1.0 M solution of borane in tetrahydrofuran, cooled in an ice bath, is added dropwise.
    5 for 30 min. 32.0 g of p-tridecyloxybenzoic acid in 450 ml of tetrahydrofuran.  After holding the mixture for 22 hours at room temperature, it is poured onto ice.  After the ice is growing The solid is filtered, washed with water to give white crystals, t.  square  72-75 ° C.  Recrystallization from ethanol gives white crystals, t.  square  74-75 0.  Example 21  O-Methanesulfonate p- (tridecyloxy) benzyl alcohol.  To a mixture of 19.1 g of p- (tridecyloxy) benzyl alcohol (prepared in accordance with the procedure of Example 20), 9.1 for (6.51 g) of triethylamine and 300 m of dichloromethane, cooled to -10 ° C, are added dropwise over 10 mi 7.5 g (5.1 ml) of methanesulfonyl chloride in 5 ml of dichloromethane.  After stirring at (-10) - (-15) for 1 h, the mixture was washed with 100 ml of ice water, 100 ml of cold 10% HCf solution, 100 ml of cold saturated sodium bicarbonate solution and 100 ml of cold, saturated solution sodium chloride and 100 ml of cold saturated sodium bicarbonate solution.  The organic layer is dried over magnesium sulfate and concentrated to a waxy solid.  Example 22  Ethyl p- (p-tridecyloxybenzyl) amino benzoate.  A mixture of 16.5 g of ethyl p-aminobenzoate, 19.1 g of p- (three decyloxy) benzyl alcohol O-methanesulfonate (prepared according to the procedure of Example 21) and 50 ml of hexamethylphosphoramide is heated for 20 h.  The solution is cooled, diluted with 100 ml of an ethanol-water mixture (1: 1), cooled again, filtered, and the solid is washed with an ethanol-water mixture (1: 1).  water and ethanol.  The resulting product is recrystallized from ethanolbenzene (7: 3). White crystals are obtained, t. . square  95-105 ° C.  Recrystallization from ethanol-benzene (9: 1) gives white crystals, m.  square  100-105 ° C.  Example 23  p- (p-tridecyloxybenzyl) amino benzoic acid.  .  A mixture of 7.0 g of ethyl p- (p-tridecyloxybenzyl) amino benzoate (prepared according to the procedure of Example 22), 7.0 g of potassium hydroxide and 150 ml of an ethanol-water mixture (9: 1) are boiled under reflux 3.5 The hot solution is acidified, diluted with water, filtered, and the solid is washed with water, thus obtaining white crystals, t.  square  110-11 and 145-150 ° C.  the product obtained is heated with 200 ml of glacial acetic acid, the solution is cooled, filtered and crystals are obtained, t.  square  110-112 and 155-160 S.  The filtrate is diluted with water.  White crystals are formed (pure according to thin layer chromatography), t.  square  108-122 and 15a-155s.  The first portion of the crista; - the solution is dissolved in 75 ml of acetone, filtered, and the filtrate is cooled and filtered. The filtrate is diluted with water and white crystals are obtained (pure by thin layer chromatography).  The two portions of pure crystals are combined, dried under vacuum, and white crystals / t are obtained.  square  110-112 and 155-160s ,.  Example 24  Ethyl p- (zinnamyl) amino benzoate.  A mixture of 33 g of ethyl p-aminobenzoate, 15.3 g of (3-chloropropenyl) benzene and 80 ml of hexamethylphosphoramide is heated on an oil bath for 21 hours.  The solution is cooled, diluted with 25 ml of water, cooled again, filtered, and the solid is washed with water, thus obtaining cream-colored crystals, t. square  123131 ° C.  Recrystallization from ethanol-benzene (9: 1) gives a pale yellow gel.  th crystals, t.  square  135-137 ° C.  White crystals are obtained by recrystallization from benzene, t.  square  135137 ° C.  Example 25  p- (Cinnamon dalamino) -benzoic acid.  A mixture of 10 g of ethyl p- (cinnamyl) amino) 1-benzoate (obtained in accordance with the procedure of Example 24), 10 g of potassium hydroxide and 200 ml of a mixture of ethanol and water (9: 1) are boiled under reflux: 3 h  The hot solution is acidified with concentrated hydrochloric acid, diluted with water, cooled, filtered and an off-white crystals are obtained.  By recrystallization from ethanol, pale yellow crystals are obtained.  square  200202С.  Example 26  Ethyl p- (3-phenylpropyl) amino3-benzoate.  A mixture of 33 g of ethyl p-aminobenzoate, 19.9 g of (3-bromopropyl) benzene and 80 ml of hexamethylphosphoramide is heated at 110 ° C for 20 h. . The mixture is cooled, diluted with 25 ml of water, CHOBS.  cooled, diluted with 50 ml of ethanol and filtered.  Solid matter  washed with cold ethanol-water mixture (1: 1) and get tan crystals, t.  Ш1.  80-83 C.  Recrystallization from ethanol is carried out twice to give tan crystals, t.  square  87-89 with.  Example 27  p- (3-Phenylpropyl) amino-benzoic acid.  A mixture of 10 g of ethkl-p- (3-phenylpropyl) amino-3-benzoate (prepared as described in Example 26), 10 g of KOH and 200 ml of an ethanol-water mixture (9: 1) are refluxed for 4 hours.  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled, filtered, and off-white crystals are obtained.  Recrystallization from ethanol gives off-white crystals, t.  pl, 1b2-163 ° C.  Example 28  Ethyl p- (10-phenyldecyl) amino-6-benzoate.  A mixture of 13.2 g of ethyl-p-aminobenzo-11, 10.1 g of phenyl disulfide, ethyl chloride, 6.0 g of sodium iodide and 50 ml of hexamethylphosphoride is heated with stirring in an oil bath at 110 ° C for 22 h.  The mixture is cooled, diluted with 25 ml of water, 25 ml of ethanol, cooled and filtered.  The solid product is washed with water in two 50 ml portions.  ethanol and get the reddish-brown crystals, t.  square  70-73 ° C. Red-brown crystals of m are obtained by recrystallization from ethanol.  square  74-76 s.  Example 29  p- (10-phenyldecyl; amino benzoic acid.  A mixture of 7.0 g of ethyl p- (10-phenyldecyl) amino benzoate (prepared according to the procedure of Example 28), 7 g of potassium hydroxide and 100 ml of an ethanol-water mixture (9: 1) are refluxed. ,five . h  The hot mixture is acidified by concentrating.  hydrochloric acid, diluted with water, cooled, filtered, and white crystals are obtained.  square  80-87 ° C Recrystallization from ethanol gives white crystals, t.  square  96-98 ° C.  Example 30.  A mixture of 18.2 g of ethyl p-aminobenzoate, 10.2 g of sodium iodide, 10.0 g of phenylpentyl chloride and 60 ml of hexamethylphosphoramide is heated under stirring at 110 ° C in an oil bath for 20 hours.  The mixture is cooled, diluted with 25 ml of water and 25 ml of ethanol, cooled and filtered.  The solid is washed with 50 ml of ethanol-water (1: 1) mixture with water and once with pit ethanol to obtain yellow crystals, t.  square  b3-64 S.  Recrystallization from ethanol is obtained not quite yellow crystals, t.  square - 73-75 C.  Example 31  p- (5-Phenylpentyl) amino benzoic acid.  A mixture of 7 g of etyl-p- (5-phenylpentyl) amino benzoate (produced as described in Example 46), 7 g of potassium hydroxide and 100 ml of a mixture of ethanol and water (9: 1) are boiled under reflux for 3 hours.  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled and filtered.  The solid is washed with water and white crystals are obtained, t.  square  141-143c.  By recrystallization from ethanol I get white crystals, t.  square  142-144 C.  Example 32  Ethyl p- (8-phenyloctyl) amino benzoate.  A mixture of 14.9 g of ethyl p-aminobeneate, 50 ml of hexamethylphosphoramide, 10.1 g of 8-phenyloctyl chloride and 6.75 g of sodium iodide is heated under stirring on an oil bath for 24 hours.  The mixture is cooled, diluted with 50 ml of water and 25 ml of ethanol, cooled and filtered.  The solid was washed with ethanol-water (1: 1), water, and white crystals were obtained, t.  square  61-68 ° C.  White crystals are obtained by recrystallization from ethanol.  mp, 75-76 ° C.  Example 33  p-8 Phenyloctyl) amino1-benzoate (prepared according to the procedure of Example 32), 7 g of potassium hydroxide and 100 ml of an ethanol-water mixture (9: 1) are refluxed for 3.5 hours.  Horus The mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled and filtered.  The solid product is washed with water and get off-white crystals, t.  square  113115 ° C.  Example 34  Ethyl p- (7-phenylheptyl) amino 1-benzoate.  A mixture of 8.25 g of ethyl p-aminobenzoate, 5.06 g of 7-phenyl heptyl chloride, 3.6 g of sodium iodide and 25 ml of hexamethylphosphoramide is heated in an oil bath for 20 hours.  The mixture was cooled, diluted with 30 ml of a mixture of ethanol and water (1: 1), water, and crystals were obtained, t.  square  65-67 ° C.  White crystals are obtained by recrystallization from ethanol.  square  66.5-68 ° C.  PRI me R.  35  p- (7-phenylhep.  thyl) amino benzoic acid.  A mixture of 5 g of ethyl-p- (7-phenylheptyl) amino-benzoate (obtained in accordance with the method of example 34).  5 g of KOH and 50 ml of ethanol-water (9: 1) are heated under reflux for 3.5 hours.  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled and filtered.  The solid is washed with water to obtain off-white crystals, t.  square  123126 ° C.  Red-brown crystals are obtained by recrystallization from ethanol.  square  123.5-125 ° C.  Example 36  p- (9-phenylnonyl) amino benzoic acid.  A mixture of 13.9 g of ethyl p-aminobenzoate, 10 g of 9-phenylnonyl chloride, 6.3 g of sodium iodide and 50 ml of hexamethylphosphoramide is heated at 110 ° C for 20 h.  The mixture is cooled, diluted with 25 ml of a mixture of ethanol-water (1: 1), water, and off-white crystals are obtained, t.  square  62-65 ° C.  The solid product is combined with 1.7 g of potassium hydroxide, 25 ml of an ethanol-water mixture (9: 1), and the resulting mixture is heated under reflux for 3.5 hours.  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, filtered, the solid product is washed with water and off-white crystals are obtained, t.  square  105-lQT C.  Example 37  4- (2-Thienyl) -butanol.  20.4 g of 4- (2-thienyl) butyric acid in 50 ml of tetrahydrofuran is added dropwise to 240 ml of a 1 M solution of borane in tetrahydrofuran cooled in an ice bath.  The mixture is left for 17 hours at room temperature and poured onto ice.  After settling, the mixture is extracted with ether, the ethereal extract is washed with water, dried over magnesium sulfate, concentrated in vacuo and a pale yellow oil is obtained.  Example 38  Ethyl p-4- (2-thienyl butyl) amino benzoate.  To a solution of 15.6 g of 4- (2-thienyl) tanol and 20.9 ml (15.2 g) of triethylamine in 500 gl of dichloromethane, cooled to -8 ° C, is added. 8.45 ml (12.5 g) of methanesulfonyl chloride dropwise over 10 minutes.  The mixture was stirred at -8 ° C for 25 minutes, washed with 400 ml of ice-cold water, 200 m of cold 10% HCE, 200 ml of cold saturated sodium bicarbonate solution and 200 ml of cold saturated sodium chloride solution.  The organic LAYER is dried over magnesium sulfate and concentrated in vacuo to an oil.  The resulting oil was combined with 33 g of ethyl p-aminobenzoate and 80 ml of hexamethylphosphoramide and a mixture of heating in an oil bath at 150-110 ° C for 19 h.  The solution is cooled, diluted with 35 ml of water, cooled, 20 ml of ethanol are added and the mixture is filtered.  The solid is washed with ethanol-water (1: 1), water and the crude product is recrystallized from 150 ml of ethanol, to obtain tan crystals, t.  square  63-65 ° C.  Red-brown crystals are obtained by recrystallization from ethanol.  square  6 67 ° C.  Example 39  (2-Thienylbutyl) amino} benzoic acid.  A mixture of 7.5 g of ethyl p-4- (2-thienylbutyl) amino-benzoate (obtained by the method of Example 38), 7.5 g of potassium hydroxide and 150 ml of a mixture of ethanol and water (9: 1) is heated under reflux in a for 4 hours  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled and filtered.  The solid product is washed with water and get snout evato brown crystals, t. square 1,140 ° C.  Recrystallization from ethanol gives reddish-brown crystals, t.  square  139-141 C Example 40.  p- (p-fluorophenethyl) amino benzoic acid.  A mixture of 15.8 g of 1- (2-chloroethyl) -4-fluorobenzene, 33 g of ethyl p-aminobenzoate, 16.6 g of potassium iodide and 100 ml of hexamethylphosphoramide is heated at 95 ° C for 15 h.  The mixture is poured into water and extracted with ether. The ether extracts are washed with water, dried over mg. Sulfate and concentrated in vacuo to an oil.  To the resulting oil were added 200 ml of an ethanol-water mixture (9: 1) and 21 g of potassium hydroxide and the mixture. boil under reflux for 35 hours.  The mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled, filtered and gray crystals are obtained. Light gray crystals are obtained by recrystallization from ethanol, t.  pl, 161-163 ° C.  PRI me R 41.  Ethyl p- 3- (0-methoxyphenyl) propylamino-benzoate.  A mixture of 14.5 g of ethyl p-aminobenzoate, 10 g of 1-bromo-3- (o-methoxyphenyl) propane and 50 ml of hexamethylphosphoramide is heated at 130 ° C for 15 hours, cooled and diluted with 20 ml of water.  The mixture is cooled, diluted with 50 ml of cold ethanol-water mixture (1: 1) and filtered.  The solid BemecT --- is washed with three portions of 50 ml each of a cold mixture of ethanol and water (1: 1), water and crystals are obtained, t. square Yub109 S.  Recrystallization from (100 ml) gives yellow crystals, t.  square  111-113 ° C.  Example 42  (o-methoxyphenyl) propylamins-benzoic acid.   A mixture of 7.0 g of ethyl p-3- (o-methoxyphenyl) propylamino-benzoyl (prepared according to the procedure described in Example 41), 7.0 g of potassium hydroxide and 100 ml of ethanol-water (9: 1) are boiled with reflux for 3.5 hours, hot solution is acidified with concentrated hydrochloric acid, diluted with water and cooled.  The mixture is filtered, the solid product is washed with water and off-white crystals are obtained, t.  square  155-157 C.  Recrystallization from ethanol gives off-white crystals, t.  square  156-158 ° C.  Example 43  (Benzyloxy) phenylpropanol-0-methanesulfonate.  To a solution of 11.0 g (benzyloxide) phenyl propanol and 10.4 ml of triethylamine in 175 ml of dichloromethane, cooled to 10 ° C, a solution of 3.89 ml of methanesulfonyl chloride in 10 ml of dichloromethane is added dropwise over 10 minutes.  The solution was stirred at -10 ° C for 30 minutes, washed with 150 ml of cold water, 75 ml of cold 10% HC, 75 ml of cold saturated sodium bicarbonate solution, 75 ml of cold saturated sodium chloride solution and dried over magnesium sulfate.  The solvent is removed in vacuo and off-white crystals are obtained, t.  square  b5-69 S.  Example 44  Ethyl p-3-p- (b zyloxy) phenyl propylamino-benzoate.  A mixture of D2.8 g of 3-p- (benzyloxy) phenyl-propanol-O-methanesulfonate (obtained by the method of example 43 50 w hexamethylphosphoramide and 16.5 ethyl-p aminobenzoate is heated at 100-105 ° C. for 17.5 hours  The mixture is cooled, diluted with 15 ml of water, 30 ml of ethanol and cooled.  In order to carry out the filtration, 100 ml of a mixture of ethanol and water (1: 1) are added to the solid, filtered, rinsed with a mixture of ethanol and water (1: 1), water and reddish-brown crystals are obtained, t, pl.  98-107c.  By recrystallization from ethanol, light yellow crystals are obtained, t, pl.  114-116 ° C.  Example 45  p-53-p- (Benzyl oxy) phenyl propylamino-benzoic acid.  A mixture of 8.0 g of ethyl p-13-p- (benzyl oxy) phenyl propylamino-benzoate (obtained by the method of example 44) 8 g of KOH and 100 ml of a mixture of ethanol and water (9: 1) are refluxed for 3.5 hours  The hot mixture is acidified with concentrated hydrochloric acid, diluted with water, cooled, filtered, the solid is washed with water, and tan crystals are obtained, t.  pl, 170172c. Recrystallization from ethanol gives off-white crystals, m, pl.  171-172s.  Example 46, b-Phenylhexano To 19 ml of a 1 M solution of borane in tetrahydrofuran, cooled in an ice bath, add 19.2 g of 6-phenylcaproic acid over 30 minutes.  The solution is stirred for 1.5 h and a 100 1 M solution of borane in tetrahydrofuran is added to it.  After stirring overnight at room temperature, the reaction mixture is poured onto 500 g of ice. The mixture is extracted with ether, the extracts are washed with water, dried over magnesium sulfate, concentrated under reduced pressure, and 6-phenylhexanol is obtained as a light yellow liquid.  An example. 47, 6-Phenylhexanol-O-methanesulfonate, To a cooled (solution of 19.4 g of 6-phenylhexanol (prepared according to the procedure described in Example 46) and 15.1 g of triethylamine in 500 ml of dichloromethane are added dropwise over 5 min 12.6 g of methanesulfonyl chloride.  The mixture was stirred at -10 ° C for 30 minutes, the solution was thoroughly washed with 200 ml of cold water, 200 ml of cold 10% hydrochloric acid, 200 cold saturated sodium bicarbonate solution and 200 ml of cold saturated sodium chloride solution.  The organic layer was dried over magnesium sulfate, the solvent was removed under reduced pressure, and 6-phenylhexanol-O-methanesulfonate was obtained as an oil.  P r and M e.  p 48.  Ethyl 4-b- (phenyl hexyl) amino benzoate.  A solution of 34.9 g of ethyl p-aminobenzoate, 26.9 g of 6-phenylhexanol-O-methanesulfonate (prepared as described in Example 47) and 200 ml of hexamethylphosphoramide are heated at an oil bath for 20 h.  The mixture is cooled, diluted with 100 ml of water and filtered.  The solid product is washed with 60 ml of ethanol-water mixture (1: 1) to obtain crude ethyl 4- (6-phenylhexylamino) benzoate.  Purification gives the desired product in the form of crystals, t.  pl, 69, 5-72,5 ° C.  Example 49  2- (2-Thienyl) ethanol-0-methanesulfonate.  A mixture of 12.8 g of 2- (2-thienyl) ethanol, 450 ml of dichloromethane and 20.2 g of triethylamine is cooled before and 12.8 g of cold methanesulfonyl chloride are added dropwise over 30 minutes.  After stirring for 1 hour, the mixture is washed with 300 ml of cold water, 300 ml of cold 10% hydrochloric acid, 300 ml of cold saturated sodium bicarbonate solution and 300 ml of cold saturated sodium chloride solution.  The organic layer is dried over magnesium sulfate, concentrated in vacuo to obtain the desired product as an oil.  Example 50  Ethyl 4- 2- (2-thienyl) ethylamino-benzoate.  A mixture of 33 g of ethyl p-aminobenzoate, 21.8 g of 2- (2-thienyl) -ethanol-0-methanesulfonate (prepared in accordance with the procedure described in Example 49) and 100 ml of hexamethylphosphorus are heated on an oil bath with 25 C for 16 hours  The mixture is cooled, diluted with 15 ml of ethanol and 150 ml of water.  The mixture is extracted with ether, the ether extracts are washed with water, dried over magnesium sulphate and concentrated in vacuo to obtain a crude oil.  A sample of the resulting oil is chromatographed on silica gel.  The fractions containing the desired product are combined, recrystallized from hexane, and ethyl 4- {2- (2-thienyl) ethylamino-benzoate is obtained in the form of yellow-tan crystals, t.  square  93-95 S.  Example 51  (2-Thienyl) -ethylamino1-benzoic acid.  A mixture of 29.7 of crude ethyl 4- (2-thienyl) ethylamino-benzoate, 29 g of potassium hydroxide and 200 ml of 95% ethanol was heated under reflux for 3 hours.  The solution is diluted with 100 ml of water and adjusted to pH 6 with concentrated hydrochloric acid.  The mixture is cooled, filtered.
    the solid is washed with ethanol-water (1: 1) and a solid is obtained. The resulting product is heated with 200 ml of ethanol, filtered, and the filtrate is concentrated. Cleaning gives the desired product, so pl. 163165 ° C.
    Example 52. p-heptyloxybenzyl alcohol.
    To a solution of 125 ml of 1 M borane in tetrahydrofuran cooled in an ice bath, 19.3 g of p-heptyloxybenzoic acid in 160 ml of tetrahydrofuran are added over 45 minutes. The mixture was stirred at room temperature for 5.5 hours, poured onto ice-water and 30 ml of concentrated hydrochloric acid was added. The mixture is filtered, the solid product is washed with water and the desired compound is obtained as a white viscous substance.
    Example 53. P-heptyloxybenzyl alcohol 0-methanesulfonate.
    A mixture of 17.7 g of p-heptyloxybenzyl alcohol {prepared according to the procedure described in Example 52), 16.7 ml of triethylamine and 380 dry dichloromethane is cooled to -90 ° C and added dropwise over 5 minutes 6.81 ml of methanesulfonyl chloride. The mixture was stirred at -9 ° C for 30 minutes and the solution was thoroughly injected with 250 ml of cold water, 200 ml of cold water, 200 ml of cold 10% hydrochloric acid, 250 ml of cold sodium bicarbonate solution and 200 ml of cold solution sodium chloride. The layer is organically dried over magnesium sulfate, the solvent is removed under reduced pressure and the desired product is obtained as a yellow oil.
    Example 54. Ethyl p-Jfn (heptyloxy) benzyl amino benzoate.
    A mixture of 13.5 g of p-(heptyloxy) benzyl alcohol O-methanesulfonate (prepared as described in Example 53), 14.9 g of ethyl p-aminobenzoate and 50 ml of hexamethylphosphoramide are heated at 120 ° C for 24 hours. The mixture is cooled, diluted 40 ml of ethanol-water mixture (1: 1) are cooled and cooled again. Filtration gives a crude product, which is recrystallized from 95% ethanol and from ethanol to give white crystals, melting at 111-113 ° C.
    Example 55 (heptyloxy) benzyl amino benzoic acid. A mixture of 5 g of ethyl p-5 p- (heptyloxy) benzyl amino benzoate (prepared according to the procedure of Example 54), 1.51 g of potassium hydroxide and 50 ml of 95% ethanol is heated under reflux for 5 Concentrated hydrochloric acid is added and the mixture is diluted with 150 ml of water. Cooling and filtering give crystals that are re-.
    crystallized from ethanol to obtain white crystals, so pl. 148152, 5С.
    Example 56. p-Decylbenzyl alcohol.
    To 69.5 ml of 1 M boron in tetrahydrofuran, cooled in an ice bath, a solution of 17.2 g of n-decylbenzoic acid in 150 ml of dry tetrahydrofuran is added dropwise over 40 minutes. The mixture was heated under reflux for 3.5 hours, cooled, 5 ml of concentrated HCl acid was added and poured onto ice. The resulting mixture is filtered, the solid is washed with water and
    5 get white crystals.
    Example 57. O-Methanesulfonate of p-decylbenzyl alcohol.
    A solution of 17.0 g of p-decylbenzyl alcohol (obtained by the method of example 56) and 14.3 ml of triethylamine in
    0 330 ml of dry dichloromethane is cooled to (-5) - (-9) s and 5.85 ml of methanesulfonyl chloride is added dropwise to it under stirring over 7 minutes. The mixture is stirred at
    5 for 30 minutes and then thoroughly washed with 250 ml of cold water. G 200 ml of cold 10% hydrochloric acid, 200 ml of cold saturated sodium bicarbonate solution and 200 ml i
    0 cold saturated solution of sodium chloride. The extract is dried over magnesium sulfate, the solvent is removed under reduced pressure, and a pale yellow oil is obtained, which solidifies on standing.
    Example 58. Ethyl p- (p-decyl) benzyl amino} benzoate.
    A mixture of 20.7 g of p-decylbenzyl alcohol O-methanesulfonate (prepared as described in Example 57) and
    0 20.5 g of ethyl p-aminobenzoate in 65 ml of hexamethylphosphoramide are heated at 115-124 ° C in an oil bath for 24 hours. The mixture is cooled, diluted with 60 ml of ethanol-water mixture
    5 (1: 1), cool, filter and get cream colored crystals, so pl. 87-90 ° C.
    Prib. 59.p- | (p-decyl). Benzyl amino benzoic acid.
    0
    A mixture of 10 g of ethyl p-C (p-decyl) benzyl amino benzoate (obtained by the method of Example 58) and 2.84 g of potassium hydroxide in 90 ml of 95% ethanol 55 refluxed for 5 hours Concentrated hydrochloric acid is then added and the mixture is diluted with 100 ml of water, filtered and crystals are obtained which are washed with water. An unpurified product is obtained. Recrystallization from ethanol gives white crystals, mp. 135-136 S.
    Example 60. Ethyl- (d-naphthyl) ethylamino-benzoate. A solution of 4.7 g of 2- (ci-naphthyl) ethyl bromide and 6, bg of ethyl p-aminobenzoate in 50 ml of hexamethylphosphoramide is stirred under heating () for 16 h. The mixture is cooled and diluted with 50 ml of water , filter and obtain the crude product, which is recrystallized from ethanol. Recrystallization gives ethyl 4- 2- (c (-naphthyl) ethyl) Mino-benzoate as white crystals, mp 104-106. EXAMPLE 61. 3- (p-Chlorophenyl) -propanol-O-mesylate A solution of 27.6 g of H- (p-chlorophenyl) -propionic acid in 50 ml of dry tetrahydrofuran is added dropwise to 180 ml of 1 M borane in tetrahydrofuran, cooled in an ice bath. After the addition, the mixture is stirred overnight at room temperature temperature and poured on ice with water (1 L). The resulting mixture is extra / ignited with ether and the ether extract is concentrated to obtain 27 g of product. This product is dissolved in in 600 ml of dichloromethane and to the solution was added from 30.3 g of triethylamine. To the cooling solution () was added dropwise over 1 hour 19.0 g of methanesulfonyl chloride. After stirring for 30 minutes, the solution was washed with 400 ml of each of the subsequent cooling solutions: 10% hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution.The organic layer is dried over magnesium sulfate and concentrated to obtain 35 g of 3- (p-chlorophenyl) propanol-O-mesylate. Etc. and meper 62, Ethyl 4- (p-chloro-phenyl) propylamino-benzoate. A solution of 49.5 g of ethyl 4-aminobenzoate, 34.9 g of 3- (p-chlorophenyl) -propanol-0-mesylate in 100 ml of hexamethylphosphoramide is heated at 125-130 ° C for 16 hours. The solution is diluted with 50 tetrahydrofuran and 50 ml of water. Cooling and filtering yield crystals that are washed with water, recrystallized from ethanol, and 28.3 g of light yellow crystals are obtained. By recrystallization, the desired product is obtained in the form of crystals, m.p. 122-124 ° C. Example 63 .. 4-.3- (p-chlorophenyl) propyl amino-benzoic acid mixture 16.3 g of methyl-4-s- (p-chlorophenyl) propylamino-benzoate, 16.3 g of potassium hydroxide and 200 mp 95% - New ethanol was heated under reflux for 3 hours. The mixture was diluted with 100 ml of water and the pH of the solution was adjusted to 6 with concentrated hydrochloric acid. Cooling and filtering give 15 g of white crystals. 8.6 g of white crystals are obtained by recrystallization from ethanol, mp 191-192 ° C, Example 64, (4-Chlorophenyl) propylamino-benzoate NaOH / d SOOI + OI / I20 Solution 40.3 g (0.139 mol) ( 4-chlorophenyl) propylaminobenzoic acid, 6.23 g (0.156 mol) of sodium hydroxide and 400 ml of absolute ethanol are heated to boiling. Enough water is added to dissolve the suspended solid (12 ml). The solution is cooled to room temperature, filtered and seeded. After filtration and drying, a first portion of the product (21.6 g) is obtained. Three more portions are recovered during subsequent evaporation of the queen cells to half the original volume, cooling, filtering and seed. Total receive 38.1. g (0,122 mol) of sodium salt. Yield 88%. For analysis, the sample is recrystallized from absolute ethanol. The sample does not have an individual melting point, but changes color over a wide range of temperatures and quickly decomposes with evolution of gases at 360 ° C. It is dried over vacuum. The analysis indicates a lack of water. After drying, the sample quickly absorbs atmospheric water. Found S: C 61.57; H 5.05, N 4.35; not 11.41. C l -jNOiClNa. . Calculated,%: C, 61.65; H 4.85, N 4.48; O 10.26; All 11.37; Na 7.0. Found,%: C 56.79; H 4.33; N 4, 02; From 10.59. C oH-fs O INa 1,5 HjO. Calculated,%: C 56.73; H 5.36; N 4.13; O 16.53, CE 10.46, Na 6.1. Example 65, (p-chlorophenyl) propylamino-benzoic acid. A solution of 0.2 mol of 4-aminobenzonitrile and 0.1 mol of 3- (p-chlorophenyl) -propanol ester of 0-methachyl sulfonic acid in 50 ml of hexamethylphosphoramide is heated for 16 hours at 125 ° C. The product is isolated and hydrolyzed with potassium hydroxide in 95% ethanol. The mixture is diluted with water and acidified with concentrated hydrochloric acid. The mixture is cooled, filtered, washed with water. 4-1.3- (p-chlorophenyl) propylamino 1-benzoic acid is obtained in the form of small crystals. Upon recrystallization, white crystals are obtained,. m.p. 192-193C.
    Example 66. (p-Chlorophenyl) propylamino-benzoic acid.
    A solution of 0.2 mol of p- (N-acetylamino) benzoic acid ethyl ester in 75 ml of hexamethylphosphoramide is cooled and 0.2 mol of sodium hydride is introduced. 0.2 mol of sodium hydride and 0.2 mol of 3 (p-chlorophenyl) propanol o-methanesulfonic acid are introduced into the mixture. The mixture is heated for 18 hours at 100 ° C. The product is distilled and hydrolyzed by mixing with a solution of potassium hydroxide in 95% ethanol at reflux temperature for 4 hours. The mixture is diluted with water, acidified with concentrated hydrochloric acid, cooled, filtered and prepared (p- chlorophenyl) propylamine benzoic acid.
    The compounds of the invention possess lipid-lowering activity in mammals, especially warm-blooded animals. Hypodipidemic activity is determined in animals as follows. The compound of the invention is administered orally with food in groups (4-6 each) of male rats (CFE view from Carworth Farms). The control group (6-8 rats) was fed with food without additives, and the experimental group with food that contained the indicated amount (% by weight of the compound according to the invention. After 6 days of treatment, the sterol concentration in the serum was determined.
    It is established that the compound possesses hypolipidemic activity if it reduces the level of serum Sterol by 15% or more than compared to the level of the control group, and / or reduces the level of triglyceride by 25% or more compared to the control samples.
    The results of the experiments are summarized in the table.
    The compounds according to the invention are useful as lipid-lowering agents for mammals when administered in an amount of 0.5 to 40 mg per 1 kg of live weight per day. The preferred dosage is to achieve optimal results of 2-29 mg per 1 kg of live weight per day. Thus, the daily dose used for a weight of about 70 kg is from 35 mg to 2.8 g, preferably from 140 mg
    5 to 2, 0
    The active compounds of the invention can be administered orally, for example, with an inert diluent or with an edible, absorbable carrier.
    0 or they can be put into hard or soft gelatin capsules, or pressed into tablets, or administered directly into food. For oral therapeutic administration, the active compounds according to isobreg-,
    5, it can be combined with carriers and used in the form of tablets, capsules, elixirs, suspensions, syrups, waffles, chewing gum and the like. Such co.mo: sites and preparations should contain at least 0.1% of the active compound. Its content in the composition and preparations may, of course, vary and be 5-75% or more of the weight of a single dosage. The amount of active compound in such therapeutic benefit compositions or preparations should be such that a suitable dosage is achieved. Preferred compositions or preparations are prepared in such a way that the single dosage contains 10-500 mg of active compound.
    Table continuation
    p- b- (phenylhexyl) amino} -6-isoic acid
    Ethyl p-ip methoxybenzyl) amino benzoate
    p- (p-tridecyloxybenzyl) amino-ben 16, 15
    60.52 16 54
    sixteen
    52
    权利要求:
    Claims (9)
    [1]
    Claim
    1. Derivatives of p- {aryl (alkyl, al-, kenyl) amino] benzoic acid total 45
    formulas π 1 ~ 00 C - / оУУН-A -R 2 WhereR 1 * 2 - hydrogen, ethyl, thienyl, s ( _ naphthyl, phenyl or phenyl substituted with phenyl- fifty A - scrap, decyloxy, o, p-methoxy, tridecyloxy, heptyloxy, decyl, benzyloxy, p-chloro, p-fluoro, 55 Where η = 1-11, or -CH = CH-CH 2 , -
    or their pharmaceutically acceptable salts having the ability to lower serum liids.
    [2]
    2. Connection by π. 1, p- [p- (de- £ 0 cyloxybenzyl) amino! -Benzoic acid.
    VNIIIPI Order 10655/71
    [3]
    3. Connection by π. 1, p- [(p-phenylundecyl) amino] benzoic acid.
    [4]
    4. Connection by π. 1, p- [b- (phenylhexyl) amino J-benzoic acid.
    [5]
    5. The compound according to π, 1, ethyl- [p- (cinnamyl) amino] benzoate.
    [6]
    6. Connection by π. 1, p- (cinnam. Milamino) benzoic acid.
    [7]
    7. Connection on π. 1, ethyl 4- [b- (phenylhexyl) amino] benzoate.
    [8]
    8. Connection by π. 1, ethyl 4- [2- (2-thienyl) ethylamino] benzoate.
    [9]
    9. Connection on π. 1, p- [p-heptyloxy (benzyl) amino] benzoic acid.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU803856A3|1981-02-07|Derivatives of p-/aryl|/-benzoic acid or their pharmacetically employed salts possessing ability to reduce lipid content in blood serum
    US3781328A|1973-12-25|Phenoxy-alkyl-carboxylic acid compounds
    AU621036B2|1992-03-05|Catechol derivatives
    US4126635A|1978-11-21|2-amino-3-|benzoylphenylacetic acids, esters and metal salts thereof
    HU183085B|1984-04-28|Process for preparing new phenoxy-alkyl-carboxylic acid derivatives and pharmaceutical compositions containing thereof
    US4350822A|1982-09-21|Antilipidemicpara-[aryl|amino]benzoic acid derivatives
    EP0239907B1|1991-09-18|Phenoxyalkanecarboxylic-acid derivatives, process for their preparation and medicines containing these compounds
    DE3317107A1|1983-11-24|IMMUNOMODULATING AGENT
    US5110831A|1992-05-05|Vinylogous hydroxamic acids and derivatives thereof as 5-lipoxygenase inhibitors
    GB1576007A|1980-10-01|Hypolipidaemic compositions
    EP0008645B1|1984-09-05|Alkoxyphenylpyrrolidones, process for their preparation and medicaments containing them
    DE3223463A1|1983-05-05|Substituted 3-azabicyclo[3.1.0]hexanes and process for the treatment of depression using substituted 3-azabicyclo [3.1.0]hexanes
    SU1053743A3|1983-11-07|Process for preparing phenylacetic acid derivatives or their salts
    FI73965C|1987-12-10|SAETT ATT FRAMSTAELLA NYA TERAPEUTISKT ANVAENDBARA DERIVAT AV ALIFATISKA FENYLKARBOXYLSYROR.
    US4500731A|1985-02-19|Derivatives of 4-phenyl-4-oxobuten-2-oic acid, pharmaceutical compositions containing them, and therapeutic uses for them
    US2744916A|1956-05-08|Phenyl-substituted salicylamides
    RU1826967C|1993-07-07|Method of synthesis of phenylhydrazones and their physiologically tolerated salts
    DE1493912A1|1969-07-10|Naphthyl acetic acids and processes for their preparation
    US4473583A|1984-09-25|Compositions containing certain derivatives of 4-phenyl-4-oxobuten-2-oic acid and methods of treatment using them
    HU180209B|1983-02-28|Process for producing substituted acyl-bracket-bicyclic aryl-bracket closed-amino alkanoic acids
    EP0012435A2|1980-06-25|Isoxazole derivatives, process for their preparation, medicines containing them and intermediates required in this process
    US4129658A|1978-12-12|4-Styryl-hexahydro-4-indolinols
    ROBINSON et al.1936|The synthesis of substituted 5, 6-benzocinchoninic acids by the Doebner and by the Pfitzinger reactions
    Blažević et al.1966|Studies on 4-Pyrones and 4-Pyridones. III. The Preparation of Some New 5-Hydroxy-1-aryl-4-pyridone-2-carboxylic Acids and Related Compounds
    US4436752A|1984-03-13|Treatment of gastric and gastro-duodenal disorders with derivatives of phenyl aliphatic carboxylic acids
    同族专利:
    公开号 | 公开日
    RO71822A|1982-02-01|
    MX3788E|1981-07-20|
    HK69179A|1979-10-05|
    ZA76902B|1977-01-26|
    DE2609962A1|1976-09-30|
    IE44285B1|1981-10-07|
    SE7602869L|1976-12-06|
    FR2303534B1|1981-08-28|
    HU173416B|1979-05-28|
    IL49012D0|1976-04-30|
    IE44285L|1976-09-12|
    DD125926A5|1977-06-01|
    AR215241A1|1979-09-28|
    YU47676A|1983-04-30|
    FR2303534A1|1976-10-08|
    NL7602332A|1976-09-14|
    BE839382A|1976-09-10|
    PL112967B1|1980-11-29|
    US4185115A|1980-01-22|
    FR2436132A1|1980-04-11|
    GB1535967A|1978-12-13|
    CH628614A5|1982-03-15|
    IL49012A|1980-12-31|
    JPS51113838A|1976-10-07|
    AU1103676A|1977-08-18|
    CS212758B2|1982-03-26|
    ES445994A1|1977-10-01|
    AU504690B2|1979-10-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3868416A|1973-10-01|1975-02-25|American Cyanamid Co|Hypolipidemic 4-benzoic acid derivatives|
    GB1576007A|1976-02-11|1980-10-01|Beecham Group Ltd|Hypolipidaemic compositions|GB1576841A|1977-01-22|1980-10-15|Beecham Group Ltd|Substituted n-acyl phenylamine compounds having hypolipidaemic activity|
    US4192884A|1977-04-07|1980-03-11|The Dow Chemical Company|Substituted 4-methyl)-amino)benzoic acids and a method for treating hypolipidemia|
    CH629796A5|1977-04-07|1982-05-14|Dow Chemical Co|Therapeutically active compounds of 4-benzoic acid|
    IL56517D0|1978-02-02|1979-03-12|American Cyanamid Co|Novel 4- amino, alkylamino or alkenylamino benzoic acids, salts and derivatives|
    US4178385A|1978-03-03|1979-12-11|The Dow Chemical Company|Method for treating hyperlipidemia in primates using 4-amino)benzoic acid|
    US4230878A|1978-03-08|1980-10-28|American Cyanamid Company|Hypolipidemic and antiatherosclerotic 4-[amino]benzoic acids and derivatives|
    US4181737A|1978-05-18|1980-01-01|The Dow Chemical Company|4-amino)benzoic acid, a method for treating hyperlipidemia, and compositions thereof|
    DE2964790D1|1978-06-23|1983-03-24|Dow Chemical Co|Hypoglycemic phenylpropynylamino benzoic acids, their salts, pharmaceutical compositions containing said compounds and their application|
    US4143151A|1978-07-03|1979-03-06|The Dow Chemical Company|Method for treating hyperglycemia in mammals using arylamino benzoic acids|
    US4207330A|1978-07-03|1980-06-10|The Dow Chemical Company|Method for treating hyperglycemia in mammals using arylamino benzoic acids|
    US4206223A|1979-01-05|1980-06-03|The Dow Chemical Company|Method for treating hyperglycemia in mammals using 4-methyl)amino)benzoic acid or derivatives thereof|
    US4281019A|1979-02-01|1981-07-28|American Cyanamid Company|4-[amino]phenyl compounds useful as hypolipidemic and antiatherosclerotic agents|
    US4263320A|1979-06-04|1981-04-21|The Dow Chemical Company|Hypoglycemic phenylpropynylamino benzoic acids|
    US4375478A|1982-03-02|1983-03-01|Abbott Laboratories|Aminobenzoic acid derivatives|
    US7214825B2|2003-10-17|2007-05-08|Honeywell International Inc.|O- hydroxylamine free base|
    WO2008121570A1|2007-03-29|2008-10-09|Irm Llc|Compounds and methods for modulating g protein-coupled receptors|
    CN109206333A|2018-10-16|2019-01-15|河南师范大学|A kind of synthetic method and application of the benzocainum monosubstituted derivative with antibacterial activity|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/557,550|US4185115A|1975-03-12|1975-03-12|Antilipidemic para-[arylamino]-benzoic acid derivatives|
    [返回顶部]