Use of agonists of formyl peptide receptor 2 for treating ocular inflammatory diseases

Patent metadata

Field	Value
Publication number	US-9850264-B2
Application number	US-201414196047-A
Country	US
Kind code	B2
Filing date	Mar 4, 2014
Priority date	Mar 6, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

The present invention relates to a method for treating ocular inflammatory diseases in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2.

First claim

What is claimed is:

1. A method of treating an ocular inflammatory disease in a subject in need of such treatment, the method comprising administering a pharmaceutical composition comprising a therapeutically effective amount of at least one formyl peptide receptor 2 (FPR2) agonist of Formula II:

wherein:
a is 1 and b is 0; a is 0 and b is 1, or a is 1 and b is 1;
R 1 is optionally substituted C 1-8 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted heterocycle, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 3-8 cycloalkenyl, -NR 11 R 12 or -OR 13 ;
R 2 is optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl; R 3 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 optionally substituted heterocycle, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl or optionally substituted C 3-8 cycloalkenyl;
R 4 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl or optionally substituted C 3-8 cycloalkenyl;
R 5 is halogen, —CF 3 or —S(O) n R 14 ;
n is 0, 1 or 2;
R 6 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl or optionally substituted C 3-8 cycloalkenyl;
R 7 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl or optionally substituted C 3-8 cycloalkenyl;
R 8 is hydrogen, optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl;
R 9 is hydrogen, optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl;
R 10 is hydrogen, optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl;
R 9a is hydrogen, optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl;
R 10a is hydrogen, optionally substituted C 1-8 alkyl or optionally substituted C 6-10 aryl;
R 11 is hydrogen or optionally substituted C 1-8 alkyl;
R 12 is hydrogen or optionally substituted C 1-8 alkyl;
R 13 is hydrogen or optionally substituted C 1-8 alkyl;
R 14 is hydrogen, CF 3 or optionally substituted C 1-8 alkyl;
and R 15 is hydrogen or optionally substituted C 1-8 alkyl;
wherein the ocular inflammatory disease is selected from the group consisting of uveitis, dry eye, keratitis, allergic eye disease, infectious keratitis, herpetic keratitis, corneal angiogenesis, lymphangiogenesis, retinitis, choroiditis, acute multifocal placoid pigment epitheliopathy, Behcet's disease, post-surgical corneal wound healing, wet age-related macular degeneration (ARMD) and dry ARMD.

2. The method of claim 1 , wherein the at least one FPR2 agonist is selected from the group consisting of:

{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- phenylpropanoyl]amino}acetic acid

3-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- phenylpropanoyl]amino}propanoic acid

{[(2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}- 3-methylpentanoyl]amino}acetic acid

{[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- methylpentanoyl]amino}acetic acid

{[(2S)-2-{[(4- bromophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid

{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}acetic acid

tert-Butyl{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- phenylpropanoyl]amino}acetate

tert-butyl 3-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- phenylpropanoyl]amino}propanoate

(2S)-2-{[(4-bromophenyl) carbamoyl]amino}- N-(2-hydroxyethyl)-3-phenylpropanamide

tert-butyl {[(2S,3S)-2-{[(4-bromo-2- fluorophenyl)carbamoyl]amino}-3- methylpentanoyl]amino}acetate

tert-butyl{[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- methylpentanoyl]amino}acetate

(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methyl-N- (2-oxopropyl)pentan

Assignees

• Allergan Inc

Inventors

• Beard Richard L
• Donello John E
• Viswanath Veena

Classifications

• A61P27/00

  Drugs for disorders of the senses · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/02

  without antiinflammatory effect · CPC title

• A61K31/197

  the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) · CPC title