IE52289B1 - 2-amino-3(halobenzoyl)-methylphenylacetic acids,esters and salts thereof - Google Patents

2-amino-3(halobenzoyl)-methylphenylacetic acids,esters and salts thereof

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Publication number
IE52289B1
IE52289B1 IE310/82A IE31082A IE52289B1 IE 52289 B1 IE52289 B1 IE 52289B1 IE 310/82 A IE310/82 A IE 310/82A IE 31082 A IE31082 A IE 31082A IE 52289 B1 IE52289 B1 IE 52289B1
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IE
Ireland
Prior art keywords
amino
compound
sodium
halobenzoyl
compounds
Prior art date
Application number
IE310/82A
Other versions
IE820310L (en
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Robins Co Inc A H
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Publication date
Application filed by Robins Co Inc A H filed Critical Robins Co Inc A H
Publication of IE820310L publication Critical patent/IE820310L/en
Publication of IE52289B1 publication Critical patent/IE52289B1/en

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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
    • A61K31/12—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
    • 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
    • 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
    • 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
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K31/22—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
    • 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
    • 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

Abstract

Novel 2-amino-3-(halobenzoyl)- methylphenylacetic acids, esters and salts having the formula: wherein R represents a hydrogen atom, a lower alkyl group or a pharmaceutically acceptable metal cation, Y represents a halogen atom and n is an integer from 1 to 3 are provided. The compounds exhibit outstanding anti-inflammatory and analgesic activity in warm blooded animals with minimal gastro-intestinal toxicity.

Description

The present Invention relates to certain 2-amino-3(halobenzoyl)-methylphenylacetic acids, their alkylesters and metal salts, pharmaceutical compositions containing such compounds and pharmaceutical uses thereof.
Certain 2-amino-3-(5 and 6) benzoylphenylacetic acids having various substituents on the benzoyl'and phenyl, moieties and the methods of preparing*and using the same are disclosed in U.S. Patent 4,045,576. The compounds of this reference are not methylphenylacetic acids or their derivatives.
U.S. Patent 4,221,716 discloses a process for the preparation of 7-acylindolin-2-ones which are intermediates in the preparation of the compounds of this invention.
The invention is more especially concerned with 2-amino3-(halobenzoyl) methylphenylacetic acids, alkylesters and metal salts having the formula: R represents a hydrogen atom or a C^-Cg alkyl group or a pharmaceutically acceptable metal cation, Y represents a halogen atom and n is an integer from 1 to 3.
The novel compounds of this invention possess valuable -2pharmaeologlcal properties and are useful as pharmaceutical agents. The compounds exhibit outstanding anti-inflammatory and analgesic activity in warm blooded animals with minimal gasto-intestinal toxicity.
The present invention encompasses the compounds of Formula X set forth above with the accompanying definitions, pharmaceutical compositions comprising the compounds of Formula X and the compounds of Formula X for use in alleviating inflammation in living animals.
Xn the definition of symbols in the formulas hereof and where they appear elsewhere throughout this specification, the terms have the following meaning and significance.
The term cx“C6 alkyl as used herein includes straight and branched chain radicals of up to six carbon atoms inclusive, preferably no more than four carbon atoms and is exemplified by such groups as methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, tertiary butyl, amyl, isoamyl and hexyl.
. The term halogen when referred to herein includes chlorine, fluorine, bromine and iodine.
Illustrative of pharmaceutically acceptable metal cations are sodium, potassium, calcium, magnesium, zinc, aluminium, copper and hydrates thereof.
The compounds of this invention are conveniently prepared from a 7-bensoylmethylindolin-2-one of the formula: -3wherein Y and n are as defined above. These starting compounds may be prepared by conventional methods, such as those disclosed in U.S. Patents 4,045,576 and 4,221,716 mentioned above. The compounds of this invention are prepared by hydrolysis of the 7-benzoylmethylindolin-2-pnes in aqueous basic solution to provide salts thereof which may then be acidified to obtain the acid. To obtain the lower alkyl esters thereof, the acid is converted to a metal salt which is then reacted in a suitable solvent with an alkyl halide to provide the desired ester.
The invention may be put into practice in various ways and a number of specific embodiments will be described to illustrate the invention with reference to the accompanying examples.
Example 1 Preparation of Sodium 2-Amino-3-(4-Fluorobenzoyl)5-Methylphenylacetate Monohydrate. 2Q A mixture of 8.0 grams (0.03 mol) of 7-(4-fluorobenzoyl)-5-methylindolin-2-one in 120 ml of 3N sodium hydroxide was heated at reflux for 16 hours. After diluting with water to 300 ml, the solution at a temperature of 50°C was titrated with concentrated hydrochloric acid to a pH of 8.2. The resulting orange solution was filtered and the filtrate obtained was cooled at 5°C and acidified ~ to a pH of 4.5 with glacial acetic acid. The resulting yellow solid was collected and washed with water, then dissolved in methylene chloride. Water was added and the on mixture was titrated with dilute sodium bicarbonate solution S2289 -4untll a pH of 7.0 was maintained. The aqueous layer was separated and concentrated by boiling with absolute ethyl alcohol so as to remove water as the azeotrope. The yellow powder obtained was dissolved in isopropyl alcohol and one ml of water was added. After allowing the mixture to stand for 3 days,' the resulting yellow solid was collected and dried at 25°C under high vacuum for 2 days to yield 1.6 grams (16.5% yield) of the title compound as a yellow powder having a m.p. of 140-160°C.
Analysis: Calculated for C^H^iNOjNa.HjO: C,58.72; H,4.62 N,4.28 Found : C,58.71; H,4.68 N,4.26 Example 2 Preparation of Sodium 2-Amino-3-(4-Chlorobenzoyl)-5Methylphenylacetate.
Following the procedure of Example 1, a mixture of 11.5 grams (0.04 mol) of 7-(4-chlorobenzoyl)-5-methylindolin2-one and 160 ml of 3 N sodium hydroxide gave, after recrystallisation from water, 2.5 grams (18%) of the title compound as orange needles, m.p. 262°C.
Analysis: Calculated for C,-H.,CU40J)a: C,59.00; H,4.02; _ . -1° 13 3 Ν,4!.3Θ Found C,58.82; H,4-09; N.4.32 Example 3 Preparation of sodium 2-Amino-3-(2,4-dlchlorobenzoyl)5-Methylphenylacetate.
Following the procedure of Example 1, a mixture of 7-(2,4-dichlorobenzoyl)-5-methylindolin-2-one and 3N 8odium hydroxide produced the title compound. -5Example 4 Preparation of Sodium 2-Amino-3-(2,3,5-Trichlorobenzoyl)-6-Methylphenylacetate.
Following the procedure of Example 1, a mixture of 7-(2,3,5-triehlorobenzoyl)-4-methylindolin-2-one and 3N sodium hydroxide produced the title compound.
Example 5 Preparation of Sodium 2-Amino-3-(4-Chlorobenzoyl)4-Methylphenylacetate.
Following the procedure of Example 1, a mixture of 4-chlorobenzoyl-6-methylindolin-2-one and 3N sodium hydroxide produced the title compound.
Generally, in the past, strong anti-inflammatory drugs have been found to produce serious side effects of gastric bleeding and ulceration when administered orally to animals in effective amounts. The compounds of the present invention have been found to have the advantage that lowered incidence of gastric irritation is observed when they are administered in effective amounts for reducing inflammation as compared to indomethacin and the 2-amino-3-benzoylphenyl-acetic acids and their derivatives disclosed in O.S. Patent 4,045,576. For example, the compound of Example 2, sodium 2-amino-3(4-chlorobenzoyl)-5-methylphenylacetate, was found to be approximately twice as potent as indomethacin and sodium 2-amino-3-benzoylphenylacetate but exhibited about. 1/4 as much irritation to the stomach as indomethacin and about 1/2 as much irritation to the stomach as sodium 2-amino-3-benzoylphenylacetate. The compound of Example 2 -6wae found to have about 1/2 the potency of sodium 2amlno-3-(4-chlorobenzoyl)-5-fluorophenylacetate but surprisingly exhibited about 1/4 as much irritation to the stomach as that compound.
The anti-inflammatory activity was demonstrated in laboratory animals using a modification of the Evans Blue-Carrageenan Pleural Effusion Assay of Sancilio, L. F., J· Pharmacol. Exp. Ther. 168; 199-204 (1969).
Gastric toxicity was determined by a modification of the method of Tsukada et al., Arzneim. Forsch. 28: 428-438 (1978).
The compounds of this invention also act as analgetics as determined by a modification of the method of Collier, et al., Brit. J. Pharmacol. Chemother. 32: 295-310 (1968).
The present invention also contemplates novel compositions containing the compounds of the invention as active ingredients. Effective quantities of any of the foregoing pharmacologically active compounds may be administered to a living animal' body in any one of various ways, for example, orally as in capsules or tablets, parenterally in the form of sterile solutions or suspensions, and in some cases intravenously in the form of sterile solutions. In forming the novel compositions of this invention, the active ingredient is incorporated in a suitable carrier, illustratively, a pharmaceutical carrier. Suitable pharmaceutical carriers which are useful in formulating the compositions of this invention include search, gelatin, glucose, magnesium carbonate, lactose and malt. Liquid compositions are also within -7the purview of this invention and suitable liguid pharmaceutical carriers include ethyl alcohol, propylene glycol, glycerine and glucose syrup.
The pharmacologically active compounds may be 5 advantageously employed in a unit dosage of from 0.1 to 150 milligrams. The unit dosage may be administered once daily or in multiple or divided daily doses. The daily dosage may vary from 0.3 to 450 milligrams. Five to 25 milligrams appears optimum per unit dose.
Ih is only necessary that the active ingredient constitute an effective amount i.e., such that a suitable effective dosage will be obtained consistent with the dosage form employed. The exact individual dosages as well as daily dosages will, of course, be determined according to standard medical principles under the direction of a physician or veterinarian.
The active agents of the invention may be combined with other pharmacologically active agents, or with buffers, antacids or the like, for administration and the proportion of the active agent in the composition may be varied widely.
The following are examples of compositions.formed in accordance with this invention.
Examples 6 A to^Sg Capsules of 5 mg (Example 6A), anc 25 mg (Example 6B) of active ingredient per capsule were prepared. With the higher amounts of active ingredient, adjustment may be made in the amount of lactose. -8Example 6A Typical blend for encapsulation Active ingredient Lactose Starch Magnesium stearate Per capsule, jsa .0 296.7 129.0 4.3 Total 435.0 mg Additional capsule formulations preferably contain a higher dosage of active ingredient and are as follows: Example 6B Ingredients Per capsule mg Active ingredient 25.0 Lactose 306.5 Starch 99.2 Magnesium stearate .4..3 Total 435.0 mg In each case the selected active ingredient was uniformly blended with lactose, starch, and magnesium stearate and the blend then encapsulated.
Capsules containing 50 mg active ingredient could also be prepared.
Example 7 A typical formulation for a tablet containing 5.0 mg of active ingredient per tablet follows. The formulation may be used for other strengths of active ingredient by adjustment of the weight of dicalcium, phosphate.
' Per tablet, mg (1) Active ingredient 5.0 <2) Com starch 13.6 (3) Com starch (paste) 3.4 (4) Lactose 79.2 (5) Dicalcium phosphate 68.0 (6) Calcium stearate 0.9 170.1 mg -9Ingedients 1, 2, 4 and 5 were uniformly blended. Ingredient 3 was prepared as a 10 per cent paste in water. The blend was granulated with starch paste and the wet mass passed through an eight mesh (US sieve) screen (which has openings of 2.38 mms). The wet granulation was dried and sized through a twelve mesh (US sieve) screen (which has openings of 1.68 mms). The dried granules were blended with calcium stearate and pressed.
Example 8 Injectable - 24 sterile solutions may be made as follows: Per cc Active ingredient .............. mg Preservative, e.g. cholorobutanol .......... 0.54 weight/volume tyater for injection ............ q.s.
The solution was prepared, clarified by filtration and filled into vials which were then sealed and autoclaved. 53289

Claims (10)

1. CIAIMS
1. λ compound having the formula: CH a CHeCOOR wherein; R represents a hydrogen atom, or aC^-Cg alkyl group or a pharmaceutically acceptable cation, Y represents a halogen atom, and n is an integer from 1 to 3. •
2. 2-Amino-3-(4-fluorobenzoyl)-5-methylphenylacetic acid.
3. Sodium 2-amino-3-(4-fluorobenzoyl)-5-methy1phenylacetate monohydrate.
4. 2-Amino-3-(4-chlorobenzoyl)-5-methylphenylacetic acid.
5. Sodium 2-amino-3-(4-chlorobenzoyl)-5-methy1phenylacetate.
6. A compound ae claimed in Claim 1 substantially as specifically described herein with reference to any one of Examples 1 to 5. -117. A pharmaceutical composition suitable for alleviating inflammation and pain in a living animal body comprising an effective amount of a compound as claimed in any one of Claims 1 to 6 and a pharmaceutically 5 acceptable carrier or diluent therefor.
7. 8. A composition as claimed in Claim 7 substantially as specifically described herein with reference to any one of Examples 6A/ 6B, '7 and 8.
8. 9. A compound as claimed in any one of Claims 1
9. 10 to 6 or a composition as claimed in Claim 7 or Claim 8 for use in alleviating inflammation in a living animal body. 10. A compound as claimed in any one of Claims 1 to 6 or a composition as claimed in Claim 7 or Claim 8
10. 15 for use in alleviating pain in a living animal body, MACLACHLAN & DONALDSON
IE310/82A 1981-02-17 1982-02-15 2-amino-3(halobenzoyl)-methylphenylacetic acids,esters and salts thereof IE52289B1 (en)

Applications Claiming Priority (1)

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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 (en) * 1996-03-11 1997-12-30 Fundacao Oswaldo Cruz Derivatives of gem-difluorphenylacetic acid and gem-difluorphenylacetamide process of their preparation and their pharmaceutical applications
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 (en) * 2000-08-14 2003-08-20 Alcon Inc METHOD OF TREATMENT OF DISORDERS RELATED TO ANGIOGENESIS
AR030346A1 (en) * 2000-08-14 2003-08-20 Alcon Inc METHOD OF TREATMENT OF NEURODEGENERATIVE DISORDERS OF THE RETINA AND HEAD OF OPTICAL NERVE
US6646003B2 (en) 2001-04-02 2003-11-11 Alcon, Inc. Method of treating ocular inflammatory and angiogenesis-related disorders of the posterior segment of the eye using an amide derivative of flurbiprofen or ketorolac
TWI358290B (en) 2004-12-02 2012-02-21 Alcon Inc Topical nepafenac formulations

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GB1226344A (en) * 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 (en) * 1975-08-13 1978-04-17 Robins Co Inc A H PROCEDURE FOR PREPARING 2-AMINO-3- (OR 5-) BENZOYL-PHENYLETIC ACIDS
FR2366015A1 (en) * 1975-11-05 1978-04-28 Robins Co Inc A H Amino-benzoyl-phenylacetic acid derivs - antiinflammatory, hypocholesterolemic and blood platelet agglomeration inhibitory activity
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

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GR76516B (en) 1984-08-10
DE3204854A1 (en) 1982-09-09
FI73970C (en) 1987-12-10
KE3454A (en) 1984-10-12
HU187644B (en) 1986-02-28
HK90384A (en) 1984-11-23
LU83928A1 (en) 1983-06-07
PL235095A1 (en) 1982-11-08
DE3204854C2 (en) 1994-06-16
CH651294A5 (en) 1985-09-13
AU7950382A (en) 1982-08-26
JPH0365338B2 (en) 1991-10-11
FI73970B (en) 1987-08-31
AT387213B (en) 1988-12-27
ATA43382A (en) 1988-05-15
GB2093027B (en) 1984-07-04
SG68584G (en) 1985-03-15
KR880002289B1 (en) 1988-10-22
PT74441B (en) 1983-08-24
PL139815B1 (en) 1987-02-28
NO820468L (en) 1982-08-18
NZ199745A (en) 1985-07-12
NO160133C (en) 1989-03-15
JPS57149256A (en) 1982-09-14
GB2093027A (en) 1982-08-25
DK67382A (en) 1982-08-18
CA1173852A (en) 1984-09-04
YU44333B (en) 1990-06-30
IL64724A0 (en) 1982-03-31
YU32582A (en) 1985-06-30
BE892156A (en) 1982-06-16
DK155936C (en) 1989-11-06
MY8500908A (en) 1985-12-31
ES8301895A1 (en) 1982-12-16
NO160133B (en) 1988-12-05
SE453387B (en) 1988-02-01
EG15798A (en) 1986-06-30
KR830008990A (en) 1983-12-16
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IT8267152A0 (en) 1982-02-10
ZA82697B (en) 1983-01-26
ES509622A0 (en) 1982-12-16
PT74441A (en) 1982-03-01
IT1157001B (en) 1987-02-11
NL8200607A (en) 1982-09-16
DK155936B (en) 1989-06-05
IE820310L (en) 1982-08-17
FR2499981B1 (en) 1986-05-23
FI820392L (en) 1982-08-18
FR2499981A1 (en) 1982-08-20

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