Topically administrable compositions containing 3-benzoylphenylacetic acid derivatives for treatment of ophthalmic inflammatory disorders

• US 5,475,034 A
• Filed: 06/06/1994
• Issued: 12/12/1995
• Est. Priority Date: 06/06/1994
• Status: Expired due to Term

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Laboratories Incorporated (Alcon Incorporated)
• Inventors: Hellberg, Mark R., Yanni, John M., Graff, Gustav
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/254,090
• Time in Patent Office: 554 Days
• Field of Search: 564/169, 514/621, 514/619, 514/617, 514/618
• US Class Current: 514/619
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07C 233/33 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/20 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms

Abstract

Novel ester and amide derivatives of 3-benzoylphenylacetic acid are disclosed. The use of these novel derivatives and certain known derivatives in topically administrable compositions for the treatment of ophthalmic inflammatory disorders is also disclosed.

Claims

1. A method of treating ophthalmic inflammatory disorders and ocular pain which comprises topically administering to the eye a pharmaceutical composition comprising an anti-inflammatory-effective amount of a 3-benzoylphenylacetic acid derivative of the formula:

##STR7## R=H, C_1-4 (un)branched alkyl, CF₃, or SR⁴, Y=NR"R'"'"',

R'"'"'=H, or C_1-10 (un)branched alkyl, (un)substituted (substitution as defined by X below),

R"=H,

X and X'"'"' independently=H, F, Cl, Br, I, OR'"'"', OH, SR⁴, CF₃, R⁴, or NO₂,

R⁴ =C_1-6 (un)branched alkyl,

m=0-3,

m'"'"'=0-5, and

W=H.

2. The method of claim 1 wherein the 3-benzoylphenylacetic acid derivative is of the formula:

##STR8## R=H, or C_1-2 alkyl Y=NR'"'"'R",

R'"'"'=H, or C_1-6 (un)branched alkyl,

X and X'"'"' independently=H, F, Cl, Br, CF₃, OR'"'"', SR⁴, or R⁴,

R"=H,

R⁴ =C_1-4 (un)branched alkyl,

m=0-2,

m'"'"'=0-2, and

W=H.

3. The method of claim 1 wherein the 3-benzoylphenylacetic acid derivative is selected from the group consisting of 2-Amino-3-(4-fluorobenzoyl)-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-benzoly-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-(4-chlorobenzoyl)-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-benzoyl-5-chloro-α

-(methylthio)-phenylacetamide, 2-Amino-3-(4-fluorobenzoyl)-α

-(methylthio)-N-(2-methozy)ethylacetamide, 2-Amino-3-(4-fluorobenzoyl)-phenylacetamide, 2-Amino-3-benzoyl-phenylacetamide, 2-Amino-3-(4-chlorobenzoyl)-phenylacetamide, 2-Amino-3-benzoyl-5-chlorophenylacetamide, 2-Amino-3-(4-fluorobenzoyl)-N-(2-methoxy)ethyl phenylacetamide, 2-Amino-3-(4-bromobenzoyl)-phenylacetamide, and 2-Amino-3-(4-bromobenzoyl)-N-methyl phenylacetamide.

4. The method claim 3 wherein the 3-benzoylphenylacetic acid derivative is selected from the group consisting of 2-Amino-3-(4-fluorobenzoyl)-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-(4-chlorobenzoyl)-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-(4-chlorobenzoyl)-α

-(n-propylthio)-phenylacetamide, 2-Amino-3-benzoyl-5-chloro-α

-(methylthio)-phenylacetamide, 2-Amino-3-(4-fluorobenzoyl)-phenylacetamide, 2-Amino-3-benzoyl-phenylacetamide, 2-Amino-3-(4-chlorobenzoyl)-phenylacetamide, 2-Amino-3-benzoyl-5-chlorophenylacetamide, and 2-Amino-3-(4-bromobenzoyl)-phenylacetamide.

5. The method of claim 4 wherein the 3-benzoylphenylacetic acid derivative is selected from the group consisting of 2-Amino-3-(4-fluorobenzoyl)-phenylacetamide, 2-Amino-3-benzoyl-phenylacetamide and 2-Amino-3-(4-chlorobenzoyl)-phenylacetamide.

6. The method of claim 1 wherein the amount of 3-benzoylphenylacetic acid is from about 0.001 to about 4.0% (w/v).

7. The method of claim 6 wherein the amount of 3-benzoylphenylacetic acid is from about 0.01 to about 0.5% (w/v).