Amide derivatives of N-urea substituted amino acids as formyl peptide receptor like-1 (FPRL-1) receptor modulators

Patent metadata

Field	Value
Publication number	US-9351948-B2
Application number	US-201514608503-A
Country	US
Kind code	B2
Filing date	Jan 29, 2015
Priority date	Oct 26, 2011
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

First claim

What is claimed is:

1. A method of treating dry eye in a subject in need of such treatment, the method comprising administering to the subject a compound of Formula II:

wherein:
a is 1 and b is 0;
R 1 is optionally substituted C 1-8 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted heterocycle, 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;
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;
R 10 is hydrogen;
R 11 is hydrogen or optionally substituted C 1-8 alkyl, provided that R 11 is not

R 12 is hydrogen;
R 13 is hydrogen or optionally substituted C 1-8 alkyl; and
R 15 is hydrogen or optionally substituted C 1-8 alkyl;
or a tautomer, hydrate or solvate thereof;
or a pharmaceutically acceptable salt of the foregoing;
provided that the compound is not:

2. The method of claim 1 , wherein:
R 1 is optionally substituted C 1-8 alkyl, —NR 11 R 12 or —OR 13 ;
R 2 is optionally substituted C 1-8 alkyl;
R 3 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 or —NR 11 R 12 ;
R 4 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 or —NR 11 R 12 ;
R 6 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 or —NR 11 R 12 ;
R 7 is hydrogen, optionally substituted C 1-8 alkyl, halogen, —COOR 15 , —OR 13 or —NR 11 R 12 ; and
R 8 is hydrogen or optionally substituted C 1-8 alkyl.

3. The method of claim 2 , wherein:
R 1 is —OR 13 ;
R 2 is unsubstituted C 1-8 alkyl;
R 3 is hydrogen;
R 4 is hydrogen;
R 6 is hydrogen;
R 7 is hydrogen; and
R 8 is hydrogen.

4. The method of claim 1 , wherein the compound is selected from:

and enantiomers, diastereoisomers, tautomers, hydrates or solvates thereof;
and pharmaceutically acceptable salts of the foregoing.

5. A method of treating dry eye in a subject in need of such treatment, the method comprising administering to the subject a therapeutically effective amount of a compound having the following structure:

or a pharmaceutically acceptable salt thereof.

6. A method of treating dry eye in a subject in need of such treatment, the method comprising administering to the subject a therapeutically effective amount of a compound having the following structure:

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , 4 , 5 or 6 , wherein the subject is a human.

Assignees

• Allergan Inc

Inventors

• Beard Richard L
• Duong Tien T
• Donello John E
• Viswanath Veena
• Garst Michael E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/00

  Drugs for disorders of the senses · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

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

• C07D233/64

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title