[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

NZ199745A - 2-amino-3-(halobenzoyl)-methylphenylacetic acid derivatives and pharmaceutical compositions - Google Patents

2-amino-3-(halobenzoyl)-methylphenylacetic acid derivatives and pharmaceutical compositions

Info

Publication number
NZ199745A
NZ199745A NZ199745A NZ19974582A NZ199745A NZ 199745 A NZ199745 A NZ 199745A NZ 199745 A NZ199745 A NZ 199745A NZ 19974582 A NZ19974582 A NZ 19974582A NZ 199745 A NZ199745 A NZ 199745A
Authority
NZ
New Zealand
Prior art keywords
compound
amino
sodium
methylphenylacetic acid
chlorobenzoyl
Prior art date
Application number
NZ199745A
Inventor
D A Walsh
D A Shamblee
Original Assignee
Robins Co Inc A H
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Robins Co Inc A H filed Critical Robins Co Inc A H
Publication of NZ199745A publication Critical patent/NZ199745A/en

Links

Classifications

    • 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
    • A61K31/185—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
    • A61K31/12—Ketones
    • 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
    • A61K31/21—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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Indole Compounds (AREA)

Description

New Zealand Paient Spedficaiion for Paient Number 1 99745 199745 Priority • Complete Specification Tilsd: i4 riV?.2" Ciess: N.Z. Pat-ent No. 192386 discloses a process for the preparation of 7-acylindolin-2-ones which are intermediates in the preparation of the compounds of this invention. summary of the invention The invention is more specially concerned with 2-amino- 3-(halobenzoyl)methylphenylacetic acids, alkylesters and metal salts having the formula: 408 199745 CH2COOR ch»-T0I Formula I wherein; R is selected from the group consisting of hydrogen, lower alkyl or a pharmaceutically acceptable metal cation, Y is halogen, and n is an integer of 1 to J.
The novel compounds of this invention possess ]_5 valuable pharmacological properties and are useful as pharmaceutical agents. The compounds exhibit outstanding anti-inflammatory and analgesic activity in warm blooded animals with minimal gastro-intestinal toxicity.
It is therefore an object of the present invention to 20 provide novel compounds and compositions. Another object is to provide a novel method for the treatment of a living animal body and especially mammalian bodies for the purposes of alleviating inflammation and pain with a minimum of side effects in the gastric and intestinal area. Additional 25 objects will be apparent to one skilled in the art and still other objects will become apparent hereinafter.
DETAILED DESCRIPTION OF THE INVENTION The present invention encompasses the compounds of Formula I set forth above with the accompanying definitions, 30 pharmaceutical compositions comprising the compounds of Formula I and the utilization of the compounds of Formula I in living animals for their pharmacological effects as set forth hereinabove and below. 408 0974 o In 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 "lower 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, 10 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, 15 aluminum, copper and hydrates thereof.
The compounds of this invention are conveniently prepared from a 7-benzoylmethylindolin-2-one of the formula: <^oUo CH£ 0=C H wherein Y and n are as defined above. These starting compounds may be prepared by conventional methods, such as 30 those disclosed in N.2. Patents 173622 and 192886 mentioned above. The compounds of this invention are prepared by hydrolysis of the 7-benzoylmethylindolin-2-ones in aqueous basic solution to provide salts thereof which may then be acidified to obtain the acid. To obtain the lower 35 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. 408 » 199745 The preparation of the compounds of this invention are more specifically illustrated by the examples which follow.
Example 1 Preparation of Sodium 2-Amino-3-(4-Fluorobenzoyl)~ -Methylphenylacetate Monohydrate.
A mixture of 8.0 grams (0.03 mol) of 7-(4-fluoro-benzoyl)-5-methylindolin-2-one in 120 ml of 3N sodium hydroxide was heated at reflux for 16 hours. After 10 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 to 5°C. and acidified to a pH of 4.5 with glacial acetic acid. The resulting 15 yellow solid was collected and washed with water, then dissolved in methylene chloride. Water was added and the mixture was titrated with dilute sodium bicarbonate solution until a pH of 7-0 was maintained. The aqueous layer was separated and concentrated by azeotroping away water with 20 absolute ethyl alcohol. 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 25 titled compound as a yellow powder having a m.p. of 140-160°C.
Analysis: Calculated for CisHi3FN03Na-HgO: 0,58.72? H,4.62; N,4.28 Found : C,58.71: H,4.68r N,4.26 Example 2 Preparation of Sodium 2-Amino-3-(4-Chlorobenzoyl)-5- Methylphenylacetate.
Following the procedure of Example 1, a mixture of 11.5 grams (0.04 mol) of 7~(4-chlorobenzoyl)-5-methylindolin-35 2-one and 160 ml of 3 N sodium hydroxide gave, after 4o8 199745 recrystallization from water, 2.5 grams (l8$) of the titled compound as orange needles, m.p. 262°c.
Analysis: Calculated for CiaHi3ClN03Na: c,59-00; H,4.02; N,4.JO Found : C,58.82; H,4.09; N,4.?2 Example 3 preparation of Sodium 2-Amino~3-(2,4-dichlorobenzoyl)-5-Methylphenylacetate.
Following the procedure of Example 1, a mixture of 7-(2,4-dichlorobenzoyl)-5-methylindolin-2-one and 3N sodium hydroxide will produce the titled compound.
Example 4 Preparation of Sodium-2-Amino-3-(2,3*5~Trichloro-benzoyl)-6-Methylphenylacetate.
Following the procedure of Example 1, a mixture of 7-(2,3j5-trichlorobenzoyl)-4-methylindolin-2-one an(3 3N sodium hydroxide will produce the titled 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 will produce the titled compound. 408 199745 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 the effective range. The compounds of the present 5 invention have been found to have the advantage that lowered incidence of gastric irritation is observed when they are administered in the effective range for reducing inflammation as compared to indomethacin and the 2-amino-3-benzoylphenyl-acetic acids and their derivatives disclosed in N.Z. Patent 10 No. 17 8622. For example, the compound of Example 2, sodium 2-amino-3-(4-chlorobenzoyl)-5-methylphenylacetate, was found to be approximately two times 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 was found to have about 1/2 the potency of sodium 2-amino-3-(4-chloro-benzoyl)-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 25 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. ^2_: 295-310 (1968). 7 408 1 99745 Formulation and Administration 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 adminis-^ tered 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 10 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 starch, gelatin, glucose, magnesium carbonate, lactose, malt and the like. Liquid compositions 15 are also within the purview of this invention and suitable liquid pharmaceutical carriers include ethyl alcohol, propylene glycol, glycerine, glucose syrup and the like.
The pharmacologically active compounds may be advantageously employed in a unit dosage of from 0.1 to 150 milligrams. 20 The unit dosage may be administered once daily or in multiple or divided daily doses. The daily dosage may vary from 0.3 to 4^0 milligrams. Five to 25 milligrams appears optimum per unit dose.
It is only necessary that the active ingredient 25 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 30 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. 4o8 199745 8 The following are examples of compositions formed in accordance with this invention. 1. Capsules Capsules of 5 nig., 25 mg., and 50 mg. of active ingredient per capsule are prepared. With the higher amounts of active ingredient, adjustment may be made in the amount of lactose.
Typical blend for Per capsule, encapsulation mg.
Active ingredient 5.0 Lactose 296.7 Starch 129.0 Magnesium stearate 4.? Total 435«0 mg.
Additional capsule formulations preferably contain a 15 higher dosage of active ingredient and are as follows: Per capsule, Ingredients mg.
Active ingredient 25-0 Lactose 306.5 Starch 99-2 2Q Magnesium stearate 4.3 Total 435*0 mg.
In each case, uniformly blend the selected active ingredient with lactose, starch, and magnesium stearate and encapsulate the blend. 2. Tablets 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 weight of dicalcium phosphate.
Per tablet, mg. l) Active ingredient 5-0 '2) Corn starch 13-6 (3) Corn starch (paste) 3-4 (4) Lactose 79-2 (5) Dicalcium phosphate 68.0 ,6) Calcium stearate 0.9 170.1 mg

Claims (1)

1. 408 199745 y Uniformly blend 1, 2, 4 and 5. Prepare 3 as a 10 per cent paste in water. Granulate the blend with starch paste and pass the wet mass through an eight mesh screen. The wet granulation is dried and sized through a twelve mesh 5 screen. The dried granules are blended with the calcium stearate and pressed. 3. Injectable - 2% sterile solutions Per cc Active ingredient 20 mg. 10 Preservative, e.g., cholorobutanol 0.5# weight/volume Water for injection q.s. Prepare solution, clarify by filtration, fill into vials, seal and autoclave. 15 Various modifications and equivalents will be apparent to one skilled in the art and may be made in the compounds, compositions, and methods of the present invention without departing from the spirit or scope thereof and it is therefore to be understood that the invention is to be 20 limited only by the scope of the appended claims. 4o8 190745 10 what */WE CLAtM K . What in rlnimrd is: - 1 - A compound selected from the group having the formula: wherein; R is selected from the group consisting of hydrogen, lower alkyl or a pharmaceutical^ acceptable cation, Y is halogen, and n is an integer of 1 to J. - 2 - The compound of claim 1 which is 2-amino~3-(4-fluoro-benzoyl)-5-methylphenylacetic acid. - 3 - The compound of claim 1 which is sodium 2-amino-3-(4-fluorobenzoyl)-5-methylphenylacetate monohydrate. - 4 - The compound of claim 1 which is 2-amino-3-(4-chloro-benzoyl)-5-methylphenylacetic acid. - 5 - The compound of claim 1 which is sodium 2-amino-3~(4-chlorobenzoyl)-5-methylphenylacetate. ~ 6 - non-human A method of alleviating inflammation in a living/animal body comprising internally administering to said living non-human animal oody an effective amount of a compound selected from the group having the formula: „ V .>• * - 408 199745 li ^ NHE c=o & <*>n wherein; R is selected from the group consisting of hydrogen, lower alkyl or a pharmaceutical^ acceptable cation? Y is halogen, and n is an integer of 1 to 3. - 7 - The method of claim 6 wherein the compound is 2-amino-3—(4-fluorobenzoyl)-5-methylphenylacetic acid. - 8 - The method of claim 6 wherein the compound is sodium 2-amino-3-(4-fluorobenzoyl)-5-methylphenylacetate mono-hydrate . - 9 - The method of claim 6 wherein the compound is 2-amino- 3-(4-chlorobenzoyl)-5-methylphenylacetic acid. - 10 - The method of claim 6 wherein the compound is sodium 2-amino-3-(4-chlorobenzoyl)-5-methylphenylacetate. - H ~ non-human A method of alleviating pain in a living/animal body non-human comprising internally administering to said living/animal body an effective amount of a compound selected from the group having the formula: 12 4o8 1 9974 wherein; R is selected from the group consisting of hydrogen, lower alkyl or a pharmaceutically acceptable cation, Y is halogen, and n is an integer of 1 to 3. - 12 - The method of claim 11 wherein the compound is 2-amino-3-(4-fluorobenzoyl)-5-methylphenylacetic acid. - 13 - The method of claim 11 wherein the compound is sodium 2-amino-3-(4-fluorobenzoyl)-5-methylphenylacetate mono-hydrate . - 14 - The method of claim 11 wherein the compound is 2-amino- 3-(4-chlorobenzoyl)-5-methylphenylacetic acid. - 15 - The method of claim 11 wherein the compound is sodium 2-amino-3-(4-chlorobenzoyl)-5-methylphenylacetic acid. - 16 - A pharmaceutical composition suitable for alleviating inflammation and pain in a living animal body comprising an effective amount of a compound selected from the group having the formula: 13 408 1 9974 CHaCOOR CH3-+0 NHg wherein; R is selected from the group consisting of hydroxy, lower alkyl or a pharmaceutically acceptable cation, Y is halogen, and n is an integer of 1 to 3, and a pharmaceutically acceptable carrier therefor. The composition as defined in claim 16 wherein the compound is 2-amino-3-(4-fluorobenzoyl)-5-methylphenylacetic acid. The composition as defined in claim 16 wherein the compound is sodium 2-amino-3~(4-fluorobenzoyl)-5-methyl-phenylacetate monohydrate. The composition as defined in claim 16 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-methylphenylacetic acid. The composition as defined in claim 16 wherein the compound is sodium 2-amino-3-(4-chlorobenzoyl)-5-methylphenylacetate . - 17 - - 18 - - 19 - - 20 - _ 14 _ 199745 i . > 21. A compound substantially as specifically described herein in any one of the Examples. 22. A method of alleviating pain and/or inflammation non-human in a living/animal body comprising internally administering to said body an effective amount of a compound f substantially as specifically described herein in any one of the Examples. 23. A pharmaceutical composition suitable for alleviating inflammation and/or pain in a living animal body comprising , . - } ' an effective amount of a compound substantially as specifically described herein in any one of the Examples and a pharmaceutically acceptable carrier therefor. > V a. 24. A method of preparation of a compound'substantially as specifically described herein in any one of the Examples. BALDWIN, SON & C.'-^ Attorneys for the
NZ199745A 1981-02-17 1982-02-16 2-amino-3-(halobenzoyl)-methylphenylacetic acid derivatives and pharmaceutical compositions NZ199745A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US23453181A 1981-02-17 1981-02-17

Publications (1)

Publication Number Publication Date
NZ199745A true NZ199745A (en) 1985-07-12

Family

ID=22881752

Family Applications (1)

Application Number Title Priority Date Filing Date
NZ199745A NZ199745A (en) 1981-02-17 1982-02-16 2-amino-3-(halobenzoyl)-methylphenylacetic acid derivatives and pharmaceutical compositions

Country Status (32)

Country Link
JP (1) JPS57149256A (en)
KR (1) KR880002289B1 (en)
AT (1) AT387213B (en)
AU (1) AU7950382A (en)
BE (1) BE892156A (en)
CA (1) CA1173852A (en)
CH (1) CH651294A5 (en)
DE (1) DE3204854C2 (en)
DK (1) DK155936C (en)
EG (1) EG15798A (en)
ES (1) ES509622A0 (en)
FI (1) FI73970C (en)
FR (1) FR2499981B1 (en)
GB (1) GB2093027B (en)
GR (1) GR76516B (en)
HK (1) HK90384A (en)
HU (1) HU187644B (en)
IE (1) IE52289B1 (en)
IL (1) IL64724A0 (en)
IT (1) IT1157001B (en)
KE (1) KE3454A (en)
LU (1) LU83928A1 (en)
MY (1) MY8500908A (en)
NL (1) NL8200607A (en)
NO (1) NO160133C (en)
NZ (1) NZ199745A (en)
PL (1) PL139815B1 (en)
PT (1) PT74441B (en)
SE (1) SE453387B (en)
SG (1) SG68584G (en)
YU (1) YU44333B (en)
ZA (1) ZA82697B (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
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
US6034266A (en) * 1996-03-11 2000-03-07 Fundacao Oswaldo Cruz-Fiocruz Gem-difluoro derivative of phenylacetamide and phenylacetic acid and their pharmaceutical uses
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
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
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CH577461A5 (en) * 1975-08-13 1976-07-15 Robins Co Inc A H
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

Also Published As

Publication number Publication date
IL64724A0 (en) 1982-03-31
KR830008990A (en) 1983-12-16
BE892156A (en) 1982-06-16
KR880002289B1 (en) 1988-10-22
DE3204854A1 (en) 1982-09-09
ZA82697B (en) 1983-01-26
JPS57149256A (en) 1982-09-14
LU83928A1 (en) 1983-06-07
PL235095A1 (en) 1982-11-08
HU187644B (en) 1986-02-28
KE3454A (en) 1984-10-12
EG15798A (en) 1986-06-30
ES8301895A1 (en) 1982-12-16
DK155936C (en) 1989-11-06
NO160133C (en) 1989-03-15
PL139815B1 (en) 1987-02-28
SE8200891L (en) 1982-08-18
MY8500908A (en) 1985-12-31
GB2093027B (en) 1984-07-04
FR2499981B1 (en) 1986-05-23
AU7950382A (en) 1982-08-26
DK67382A (en) 1982-08-18
FI73970B (en) 1987-08-31
FR2499981A1 (en) 1982-08-20
GB2093027A (en) 1982-08-25
IE820310L (en) 1982-08-17
NO820468L (en) 1982-08-18
IT1157001B (en) 1987-02-11
DK155936B (en) 1989-06-05
FI73970C (en) 1987-12-10
NO160133B (en) 1988-12-05
PT74441B (en) 1983-08-24
HK90384A (en) 1984-11-23
JPH0365338B2 (en) 1991-10-11
YU44333B (en) 1990-06-30
SG68584G (en) 1985-03-15
NL8200607A (en) 1982-09-16
SE453387B (en) 1988-02-01
FI820392L (en) 1982-08-18
ES509622A0 (en) 1982-12-16
IT8267152A0 (en) 1982-02-10
CA1173852A (en) 1984-09-04
CH651294A5 (en) 1985-09-13
PT74441A (en) 1982-03-01
YU32582A (en) 1985-06-30
IE52289B1 (en) 1987-09-02
AT387213B (en) 1988-12-27
ATA43382A (en) 1988-05-15
DE3204854C2 (en) 1994-06-16
GR76516B (en) 1984-08-10

Similar Documents

Publication Publication Date Title
US4126635A (en) 2-amino-3-(5- and 6-)benzoylphenylacetic acids, esters and metal salts thereof
US4503073A (en) 2-Amino-3-(alkylthiobenzoyl)-phenylacetic acids
US4249021A (en) Indanacetic acid compounds
NZ199745A (en) 2-amino-3-(halobenzoyl)-methylphenylacetic acid derivatives and pharmaceutical compositions
US4254146A (en) 3-Benzoyl-2-nitrophenylacetic acids, metal salts, amides and esters
JPH059424B2 (en)
GB2045756A (en) Hydroxy derivatives of 2- isopropylamino-pyrimidine
JPS5989671A (en) 2,5-piperazione derivative
GB2071086A (en) 2-Amino-3-[Hydroxy(phenyl)- methyl]phenylacetic acids, esters and amides
US4198431A (en) Alkyl N-(3-trifluoromethylphenyl)-anthranilate
US3923996A (en) 3-Substituted-oxindoles in compositions and methods of treating obesity
CA1147746A (en) 2-amino-3-(alkylthiobenzoyl)phenylacetic acids
US3005818A (en) 1-phenyl-2, 3-dimethyl-4-morpholino methyl pyrazolone-(5) compounds
US4333951A (en) 2-Amino-6-biphenylacetic acids
US4263281A (en) Oxaalkanoate anti-ulcer composition
EP0089426B1 (en) 2-amino-6-biphenylacetic acids
US4092426A (en) Novel aminobenzoic acid derivatives, process for preparing the same and pharmaceutical composition containing the same
US5091547A (en) Phenylacetic acid derivative and process for making same
EP0258048B1 (en) 2-amino-3-aroyl-gamma-oxobenzenebutanoic acids and esters
US4098887A (en) Pharmaceutical compositions and methods of producing antiarthritic activity with bis(pyridine)gold(1+) salts
US4314060A (en) Oxaalkanoate anti-ulcer compounds
US4440691A (en) Indancarboxylic acid zinc salts
US4855447A (en) 2-amino-3-aroyl-γ-oxobenzenebutanoic acid and esters
KR810000473B1 (en) Preparation of N-2,6-dichlorophenyl-2-aminopyrimidine
NL8001203A (en) Antitussive and analgesic di:glaucine phosphate - having no unpleasant flavour, suitable for oral admin.