PL139815B1 - Method of obtaining novel 2-amino-3-/halogenobenzoilo/-methylphenylacetic acids in the form of salts - Google Patents
Method of obtaining novel 2-amino-3-/halogenobenzoilo/-methylphenylacetic acids in the form of salts Download PDFInfo
- Publication number
- PL139815B1 PL139815B1 PL1982235095A PL23509582A PL139815B1 PL 139815 B1 PL139815 B1 PL 139815B1 PL 1982235095 A PL1982235095 A PL 1982235095A PL 23509582 A PL23509582 A PL 23509582A PL 139815 B1 PL139815 B1 PL 139815B1
- Authority
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- Poland
- Prior art keywords
- amino
- salts
- acids
- halogenobenzoilo
- formula
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 10
- 150000003839 salts Chemical class 0.000 title claims description 8
- 239000002253 acid Substances 0.000 title description 5
- 150000007513 acids Chemical class 0.000 title description 5
- 150000001768 cations Chemical class 0.000 claims description 4
- 239000012670 alkaline solution Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- UFZNNOHNAOYQQP-UHFFFAOYSA-N 7-phenacyl-1,3-dihydroindol-2-one Chemical class C=1C=CC=2CC(=O)NC=2C=1CC(=O)C1=CC=CC=C1 UFZNNOHNAOYQQP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Chemical class 0.000 description 4
- 239000002184 metal Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- YVKSMFUEDUPYIF-UHFFFAOYSA-N 3-oxo-2,3-diphenylpropanoic acid Chemical class C=1C=CC=CC=1C(C(=O)O)C(=O)C1=CC=CC=C1 YVKSMFUEDUPYIF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010053155 Epigastric discomfort Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- -1 for example Chemical compound 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- PZLOEWPWHWLNOZ-UHFFFAOYSA-N 1-benzoyl-3h-indol-2-one Chemical class O=C1CC2=CC=CC=C2N1C(=O)C1=CC=CC=C1 PZLOEWPWHWLNOZ-UHFFFAOYSA-N 0.000 description 1
- GEVQCJAIVLZAMK-UHFFFAOYSA-N 7-(4-chlorobenzoyl)-5-methyl-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C(C(=O)C=2C=C(C=C3CC(NC23)=O)C)C=C1 GEVQCJAIVLZAMK-UHFFFAOYSA-N 0.000 description 1
- WQRSNHWRHMQPLP-UHFFFAOYSA-N 7-(4-fluorobenzoyl)-5-methyl-1,3-dihydroindol-2-one Chemical compound C=1C(C)=CC=2CC(=O)NC=2C=1C(=O)C1=CC=C(F)C=C1 WQRSNHWRHMQPLP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- GQSXJNIEJJXXBZ-UHFFFAOYSA-N O.C(C)(=O)OC1=C(C(=CC(=C1)C)C(C1=CC=C(C=C1)F)=O)N.[Na] Chemical compound O.C(C)(=O)OC1=C(C(=CC(=C1)C)C(C1=CC=C(C=C1)F)=O)N.[Na] GQSXJNIEJJXXBZ-UHFFFAOYSA-N 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- SOYCMDCMZDHQFP-UHFFFAOYSA-N amfenac Chemical class NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1 SOYCMDCMZDHQFP-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical class OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- MJAQSCHBMPGJES-UHFFFAOYSA-M sodium (2-amino-3-benzoylphenyl)acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 MJAQSCHBMPGJES-UHFFFAOYSA-M 0.000 description 1
- LXVZJYNCJIPXQV-UHFFFAOYSA-M sodium;2-[2-amino-3-(4-chlorobenzoyl)-5-fluorophenyl]acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=C(F)C=C1C(=O)C1=CC=C(Cl)C=C1 LXVZJYNCJIPXQV-UHFFFAOYSA-M 0.000 description 1
- WNCLIUXXSKAOND-UHFFFAOYSA-M sodium;2-[2-amino-3-(4-chlorobenzoyl)-5-methylphenyl]acetate Chemical compound [Na+].CC1=CC(CC([O-])=O)=C(N)C(C(=O)C=2C=CC(Cl)=CC=2)=C1 WNCLIUXXSKAOND-UHFFFAOYSA-M 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
- C07C57/32—Phenylacetic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
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Description
**** Uff Twórcawynalazku Uprawniony z patentu: A. H. Robins Company, Inc., Richmond (St. Zjedn. Ameryki) Sposób wytwarzania nowych kwasów 2-amino-3-(chlorowcobenzoilo)-metylofenylooctowych w postaci soli Przedmiotem wynalazku jest sposób wytwarzania nowych kwasów 2-amino-3-(chlorowco- benzoilo)-metylofenylooctowych w postaci soli.Z opisu patentowego St. Zjednoczonych Ameryki nr 404 5576 znane sa pewne kwasy 2-amino- 3-(5 i 6) benzoilofenylooctowe majace rózne podstawniki w czesci benzoilowej i fenylowej, sposoby ich wytwarzania oraz zastosowania. Jednakze te znane zwiazki nie sa kwasami metylofenyloocto- wymi ani ich pochodnymi.Z opisu patentowego St. Zjednoczonych Ameryki nr 4 221 716 znanyjest sposób wytwarzania 7-acyloindolino-2-onów, które sa zwiazkami wyjsciowymi w sposobie wedlug wynalazku.W opisie patentowym St. Zjednoczonych Ameryki nr 4045 576 ujawniono kwasy 2-amino-3- (5-i 6-) benzoilofenylooctowe, ich estry i sole z metalami o wzorze 3, w którym R oznacza atom wodoru lub nizsza grupe alkilowa, R1 oznacza atom wodoru lub nizsza grupe alkilowa, atom sodu lub potasu, R oznacza atom wodoru, chlorowca lub nizsza grupa alkoksylowa. X oznacza atom wodoru, nizsza grupe alkilowa, atom chlorowca, grupe nitrowa lub trifluorometylowa, Y oznacza atom wodoru, nizsza grupe alkilowa, atom chlorowca, grupe nitrowa lub trifluorometylowa a A/i pierwszorzedowa grupe aminowa (-NH2), metyloaminowa lub dimetyloaminowa. Ujawnione zwiazki wytwarza sie przez hydrolize 4-(5- i 7-) benzoiloindolin-2-onów uzyskujac kwasy 2-amino- 3-(5- i 6-) benzoilofenylooctowe, w których czesc aminowa jest pierwszorzedowa grupa aminowa.Wolne kwasy przeprowadza sie w estry i sole z metalem. Opisane tu zwiazki wykazuja aktywnosc przeciwzapalna, sa efektywne przy zmniejszaniu poziomu cholesterolu u szczurów z hiperlipemia i powstrzymuja agregacje plytek krwi.Przedmiotem wynalazku jest sposób wytwarzania kwasów 2-amino-3-(chlorowcobenzoilo) metylofenyooctowych w postaci soli, objetych wzorem 1, w którym R oznacza farmaceutycznie dopuszczalny kation metalu, Y oznacza atom chlorowca.Wytwarzane sposobem wedlug wynalazku nowe zwiazki wykazuja cenne wlasciwosci farma¬ kologiczne i sa uzyteczne jako srodki farmaceutyczne. Zwiazki wykazuja znakomite dzialanie przeciwzapalne i znieczulajace dla zwierzat cieplokrwistych przy minimalnej toksycznosci zoladkowo-jelitowej.2 139815 Uzyty w opisie termin „nizszy rodnik alkilowy" obejmuje rodniki o prostym lub rozgalezio¬ nym lancuchu, zawierajace do 6 atomów wegla, korzystnie nie wiecej niz 4 atomy wegla, takie jak np. metylowy, etylowy, propylowy, izopropylowy, butylowy, Il-rzed. butylowy, amylowy, izoamy- lowy i heksylowy.Termin ..chlorowiec" obejmuje chlor, fluor, fluor, brom i jod. Przykladami farmaceutycznie dopuszczalnych kationów metalu sa sód, potas, wapn, magnez, cynk, glin, miedz i ich wodziany.Sposób wedlug wynalazku (wytwarzania zwiazków) o wzorze 1 polega na tym, ze poddaje sie hydrolizie 7-benzoilometyloidolino-2-ony o wzorze 2, w którym Y ma wyzej podane znaczenie, w wodnym roztworze zasadowym.Znane dotychczas silne srodki przeciwzapalne wywolywaly zazwyczaj powazne dzialanie uboczne, takie jak krwawienie i owrzodzenie zoladka przy podawaniu doustnym w dawkach efektywnych. Stwierdzono, ze zwiazki wytwarzane sposobem wedlug wynalazku wykazuja korzystniejsze dzialanie obnizenia podraznienia zoladka przy podawaniu w dawkach efektywnych w celu obnizenia zapalenia, w porównaniu z indometacyna i kwasami 2-amino-3-benzoilofenylo- octowymi i ich pochodnymi, opisanymi w opisie patentowym St. Zjedn. Ameryki nr 4 045 576. Np. stwierdzono, ze zwiazek z przykladu II 2-amino-3-(4-chlorobenzoilo)-5-metylofenyooctan sodu jest w przyblizeniu dwukrotnie silniejszy w dzialaniu niz indometacyna i 2-amino-3-benzoilofenylo- octan sodu, a przy tym wykazuje okolo 1/4 dzialania podrazniajacego zoladek w porównaniu z metacyna i 1/2 w porównaniu z 2-amino-3-benzoilofenylooctanem sodu. Stwierdzono, ze zwiazek z przykladu II wykazuje okolo 1/2 sily dzialania w porównaniu z 2-amino-3-(4-chlorobenzoilo)-5- fluorofenylooctanem sodu lecz niespodziewanie wykazuje okolo 1/4 dzialania podrazniajacego zoladek w porównaniu z tym zwiazkiem.Dzialanie przeciwzapalne wykazano na zwierzetach laboratoryjnych, stosujac zmodyfiko¬ wana metode Evans Blue-Carrageenan Pleural Effusion Assay of Sancilio, L.F.,J. Pharmacol.Exp. Ther. 168, 199-204 (1969).Toksycznosc zoladkowa okreslano zmodyfikowana metoda Tsukada i wspólpracownicy, Arzneim. Forsch. 28, 428-438 (1978).Dzialanie zwiazków wytwarzanych sposobem wedlug wynalazku jako srodków znieczulaja¬ cych okreslano zmodyfikowana metoda Collier i wspólpracownicy, Brit. J. Phafmacol. Chemot- her. 32,295-310(1968).Zwiazki wytwarzane sposobem wedlug wynalazku formuluje sie w preparaty farmaceutyczne, zawierajace efektywna ilosc skladnika czynnego. Moga one byc podawane zyjacym organizmom zwierzecym róznymi drogami, np. doustnie w postaci kapsulek lub tabletek, pozajelitowo w postaci sterylnych roztworów lub zawiesin i, w niektórych przypadkach, dozylnie w postaci sterylnych roztworów.Przy formulowaniu preparatów skladnik aktywny laczy sie z odpowiednim nosnikiem, np. nosnikiem farmaceutycznym. Takimnosnikiem moze byc skrobia, zelatyna, glukoza, weglan magnezu, laktoza, slód i podobne. Mozna wytwarzac równiez ciekle preparaty, przy czym ciekle nosniki farmaceutyczne obejmuja alkohol etylowy, glikol propylenowy, gliceryne, syrop gluko¬ zowy i podobne.Zwiazki farmakologicznie czynne stosuje sie korzystnie w dawkach jednostkowych 0,1- -150 mg, podawanych badz jednorazowo w ciagu dnia, badz wielokrotnie lub podzielonych na kilka dziennych dawek. Dawka dzienna moze wynosic 0,3-450 mg. Dawka jednostkowa opty¬ malna wynosi 5-25 mg.Jest równiez konieczne, aby skladnik aktywny stanowil ilosc efektywna, a mianowicie taka aby odpowiednia otrzymana dawka efektywna byla zgodna z zastosowana postacia dawki. Indy¬ widualne dawki, jak równiez dzienne dawki sa oczywiscie okreslane zgodnie ze standardowymi zasadami medycyny pod kierunkiem lekarza lub weterynarza.Wytwarzane sposobem wedlug wynalazku zwiazki aktywne mozna laczyc z innymi farmako¬ logicznymi srodkami albo z buforami, srodkami zobojetniajacymi kwasy lub podobnymi.Nastepujace przyklady ilustruja sposób wedlug wynalazku.Przyklad I. Wytwarzanie jednowodzianu 2-amino-3-(4-fluorobenzoilo)-5-metylofenylo- octanu sodu.Mieszanine 8 g (0,03 mola) 7-(4-fluorobenzoilo)-5-metyloindolino-2-onu w 120 ml 3 n wodoro¬ tlenku sodu utrzymuje sie w stanie wrzenia pod chlodnica zwrotna w ciagu 16 godzin. Po139 815 3 rozcienczeniu mieszaniny woda do 300 ml, roztwór miareczkuje sie w temperaturze 50°C stezonym kwasem solnym do wartosci pH 8,2. Otrzymany pomaranczowy roztwór przesacza sie, przesacz oziebia do 5°C i zakwasza do wartosci pH 4,5 lodowatym kwasem octowym. Otrzymane zólte cialo stale oddziela sie i przemywa woda, a nastepnie rozpuszcza w chlorku metylenu. Do roztworu dodaje sie wody i mieszanine miareczkuje rozcienczonym roztworem kwasnego weglanu sodu do wartosci pH 7. Warstwe wodna oddziela sie i zateza przez azotropowa destylacje wody z absolut¬ nym alkoholem etylowym. Otrzymany zólty proszek rozpuszcza sie w alkoholu izopropylowym i dodaje 1 ml wody. Mieszanine odstawia sie na 3 dni i nastepnie odsacza cialo stale barwy zóltej i suszy w 25°C pod zmniejszonym cisnieniem w ciagu 2 dni. Otrzymuje sie 1,6 g (wydajnosc 16,5%) produktu w postaci zóltego proszku o temperaturze topnienia 140-160°C.Analiza: dla Ci6Hi3 FN03Na-H20 Obliczono: C 58,72 H 4,62 N 4,28% Znaleziono: C 58,71 H 4,68 N 4,26% Przyklad II. Wytwarzanie 2-amino-3-(4-chlorobenzoilo)-5-metylofenylooctanu sodu.Postepuje sie w sposób opisany w przykladzie I, poddajac reakcji mieszanine 11,5 g (0,04 mola) 7-(4-chlorobenzoilo)-5-metyloindolino-2-onu i 160 ml 3 n wodorotlenku sodu. Po rekrystalizacji z wody otrzymuje sie 2,5 g (18%) produktu w postaci pomaranczowych igiel o temperaturze topnie¬ nia 262°C.Analiza: dla Ci6Hi3CIN03Na Obliczono: C 59,00 H 4,02 N 4,30% Znaleziono: C 58,82 H 4,09 N 4,32% Zastrzezenie patentowe Sposób wytwarzania nowych kwasów 2-amino-3-(chlorowcobenzoilo)-metylofenylo- octowych w postaci soli o wzorze l, w którym R oznacza farmaceutycznie dopuszczalny kation, Y oznacza atom chlorowca, znamienny tym, ze 7-benzoilometyloindolino-2-ony o wzorze 2, w którym Y ma wyzej podane znaczenie, poddaje sie hydrolizie w wodnym zasadowym roztworze.139815 CH2COOR C=0 Y WZÓR 1 WZÓR 2 CHRCOOR Am 1 WZÓR 3 Pracownia Poligraficzna UP PRL. Naklad 100 egz.Cena 130 zl PL PL PL PL
Claims (1)
1. Zastrzezenie patentowe Sposób wytwarzania nowych kwasów 2-amino-3-(chlorowcobenzoilo)-metylofenylo- octowych w postaci soli o wzorze l, w którym R oznacza farmaceutycznie dopuszczalny kation, Y oznacza atom chlorowca, znamienny tym, ze 7-benzoilometyloindolino-2-ony o wzorze 2, w którym Y ma wyzej podane znaczenie, poddaje sie hydrolizie w wodnym zasadowym roztworze.139815 CH2COOR C=0 Y WZÓR 1 WZÓR 2 CHRCOOR Am 1 WZÓR 3 Pracownia Poligraficzna UP PRL. Naklad 100 egz. Cena 130 zl PL PL PL PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23453181A | 1981-02-17 | 1981-02-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL235095A1 PL235095A1 (pl) | 1982-11-08 |
| PL139815B1 true PL139815B1 (en) | 1987-02-28 |
Family
ID=22881752
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1982235095A PL139815B1 (en) | 1981-02-17 | 1982-02-16 | Method of obtaining novel 2-amino-3-/halogenobenzoilo/-methylphenylacetic acids in the form of salts |
Country Status (32)
| Country | Link |
|---|---|
| JP (1) | JPS57149256A (pl) |
| KR (1) | KR880002289B1 (pl) |
| AT (1) | AT387213B (pl) |
| AU (1) | AU7950382A (pl) |
| BE (1) | BE892156A (pl) |
| CA (1) | CA1173852A (pl) |
| CH (1) | CH651294A5 (pl) |
| DE (1) | DE3204854C2 (pl) |
| DK (1) | DK155936C (pl) |
| EG (1) | EG15798A (pl) |
| ES (1) | ES8301895A1 (pl) |
| FI (1) | FI73970C (pl) |
| FR (1) | FR2499981B1 (pl) |
| GB (1) | GB2093027B (pl) |
| GR (1) | GR76516B (pl) |
| HK (1) | HK90384A (pl) |
| HU (1) | HU187644B (pl) |
| IE (1) | IE52289B1 (pl) |
| IL (1) | IL64724A0 (pl) |
| IT (1) | IT1157001B (pl) |
| KE (1) | KE3454A (pl) |
| LU (1) | LU83928A1 (pl) |
| MY (1) | MY8500908A (pl) |
| NL (1) | NL8200607A (pl) |
| NO (1) | NO160133C (pl) |
| NZ (1) | NZ199745A (pl) |
| PL (1) | PL139815B1 (pl) |
| PT (1) | PT74441B (pl) |
| SE (1) | SE453387B (pl) |
| SG (1) | SG68584G (pl) |
| YU (1) | YU44333B (pl) |
| ZA (1) | ZA82697B (pl) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683242A (en) * | 1985-10-28 | 1987-07-28 | A. H. Robins Company, Incorporated | Transdermal treatment for pain and inflammation with 2-amino-3-aroylbenzeneacetic acids, salts and esters |
| US5475034A (en) * | 1994-06-06 | 1995-12-12 | Alcon Laboratories, Inc. | Topically administrable compositions containing 3-benzoylphenylacetic acid derivatives for treatment of ophthalmic inflammatory disorders |
| BR9600975A (pt) * | 1996-03-11 | 1997-12-30 | Fundacao Oswaldo Cruz | Derivados do ácido gem-difluorfenilacético e de gem-difluorfenilacetamida processo de sua preparação e suas aplicações farmacêuticas |
| US6034266A (en) * | 1996-03-11 | 2000-03-07 | Fundacao Oswaldo Cruz-Fiocruz | Gem-difluoro derivative of phenylacetamide and phenylacetic acid and their pharmaceutical uses |
| AR030345A1 (es) * | 2000-08-14 | 2003-08-20 | Alcon Inc | Metodo de tratamiento de desordenes relacionados con angiogenesis |
| AR030346A1 (es) | 2000-08-14 | 2003-08-20 | Alcon Inc | Metodo de tratamiento de desordenes neurodegenerativos de la retina y cabeza de nervio optico |
| WO2002078681A2 (en) | 2001-04-02 | 2002-10-10 | Alcon, Inc. | Method of treating ocular inflammatory and angiogenesis-related disorders using an amide derivative of flubiprofen or ketorolac |
| TWI358290B (en) | 2004-12-02 | 2012-02-21 | Alcon Inc | Topical nepafenac formulations |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1226344A (pl) * | 1967-07-31 | 1971-03-24 | ||
| US3997368A (en) * | 1975-06-24 | 1976-12-14 | Bell Telephone Laboratories, Incorporated | Elimination of stacking faults in silicon devices: a gettering process |
| SE400966B (sv) * | 1975-08-13 | 1978-04-17 | Robins Co Inc A H | Forfarande for framstellning av 2-amino-3-(eller 5-)bensoyl-fenylettiksyror |
| FR2366015A1 (fr) * | 1975-11-05 | 1978-04-28 | Robins Co Inc A H | Nouveaux acides amino-2 benzoyl-3 (5 et 6) phenylacetiques et leurs esters et sels de metaux alcalins, utiles notamment comme anti-inflammatoires, et leur procede de preparation |
| IL61945A (en) * | 1980-02-19 | 1984-09-30 | Robins Co Inc A H | 2-amino-3-(hydroxy(phenyl)methyl)phenylacetic acids,esters and amides and pharmaceutical compositions containing them |
-
1982
- 1982-01-07 IL IL64724A patent/IL64724A0/xx not_active IP Right Cessation
- 1982-01-14 AU AU79503/82A patent/AU7950382A/en not_active Abandoned
- 1982-01-24 EG EG8228A patent/EG15798A/xx active
- 1982-02-01 JP JP57014710A patent/JPS57149256A/ja active Granted
- 1982-02-03 ZA ZA82697A patent/ZA82697B/xx unknown
- 1982-02-05 AT AT0043382A patent/AT387213B/de not_active IP Right Cessation
- 1982-02-08 FI FI820392A patent/FI73970C/fi not_active IP Right Cessation
- 1982-02-09 CH CH791/82A patent/CH651294A5/fr not_active IP Right Cessation
- 1982-02-09 LU LU83928A patent/LU83928A1/fr unknown
- 1982-02-10 IT IT67152/82A patent/IT1157001B/it active
- 1982-02-11 DE DE3204854A patent/DE3204854C2/de not_active Expired - Fee Related
- 1982-02-12 GB GB8204137A patent/GB2093027B/en not_active Expired
- 1982-02-15 GR GR67320A patent/GR76516B/el unknown
- 1982-02-15 IE IE310/82A patent/IE52289B1/en not_active IP Right Cessation
- 1982-02-15 YU YU325/82A patent/YU44333B/xx unknown
- 1982-02-15 SE SE8200891A patent/SE453387B/sv unknown
- 1982-02-16 PT PT74441A patent/PT74441B/pt not_active IP Right Cessation
- 1982-02-16 FR FR8202507A patent/FR2499981B1/fr not_active Expired
- 1982-02-16 NZ NZ199745A patent/NZ199745A/en unknown
- 1982-02-16 PL PL1982235095A patent/PL139815B1/pl unknown
- 1982-02-16 KR KR8200673A patent/KR880002289B1/ko active
- 1982-02-16 HU HU82464A patent/HU187644B/hu unknown
- 1982-02-16 CA CA000396392A patent/CA1173852A/en not_active Expired
- 1982-02-16 NO NO820468A patent/NO160133C/no unknown
- 1982-02-16 NL NL8200607A patent/NL8200607A/nl not_active Application Discontinuation
- 1982-02-16 DK DK067382A patent/DK155936C/da not_active IP Right Cessation
- 1982-02-16 ES ES509622A patent/ES8301895A1/es not_active Expired
- 1982-02-16 BE BE0/207327A patent/BE892156A/fr not_active IP Right Cessation
-
1984
- 1984-09-17 KE KE3454A patent/KE3454A/xx unknown
- 1984-09-21 SG SG68584A patent/SG68584G/en unknown
- 1984-11-15 HK HK903/84A patent/HK90384A/xx unknown
-
1985
- 1985-12-30 MY MY908/85A patent/MY8500908A/xx unknown
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