Dimethylbenzoic acid compounds

Patent metadata

Field	Value
Publication number	US-2016251306-A1
Application number	US-201415030891-A
Country	US
Kind code	A1
Filing date	Dec 11, 2014
Priority date	Dec 17, 2013
Publication date	Sep 1, 2016
Grant date	—

Abstract

The present invention provides a compound of the Formula I: wherein A is: and W, Y, X, R 1 , R 2 , R 3 , and R 4 are as defined herein, or a pharmaceutically acceptable salt thereof, for use as an inhibitor of the EP4 receptor.

First claim

1 . A compound of the formula:

wherein A is:

W is CH or N;
Y is CH or N;
X is CH or N;
R 1 is CH 3 , CF 3 , or F;
R 2 is H, F, Cl, CH 3 , CF 3 , CH 2 OH, CH 2 CH 2 OH, CH 2 OCH 3 , OCH 3 , OCF 3 , or CN;
R 3 is H or F; or
R 2 and R 3 together are a OCH 2 O group attached to vicinal carbon atoms;
R 4 is H, Cl, or CH 2 OH;
or a pharmaceutically acceptable salt thereof.

2 . The compound or salt according to claim 1 of the formula:

3 . The compound or salt according to claim 2 of the formula:

4 . The compound or salt according to claim 3 wherein A is:

5 . The compound or salt according to claim 4 wherein R 1 is CH 3 .

6 . The compound or salt according to claim 5 wherein R 3 is H.

7 . The compound or salt according to claim 6 wherein R 2 is CH 2 OH, CH 2 CH 2 OH, or OCH 3 .

8 . The compound or salt according to claim 7 wherein R 2 is CH 2 OH.

9 . The compound or salt according to claim 5 wherein R 2 and R 3 together are a OCH 2 O group attached to vicinal carbon atoms.

10 . The compound or salt according to claim 4 wherein R 4 is Cl.

11 . The compounds or salts thereof according to claim 1 which are:
3-[[6-(1,3-benzodioxol-5-yl)-3-methyl-pyridine-2-carbonyl]amino]-2,4-dimethyl-benzoic acid;
3-[[6-[3-(hydroxymethyl)phenyl]-3-methyl-pyridine-2-carbonyl]amino]-2,4-dimethyl-benzoic acid; and
3-[[3-(3-chlorophenyl)naphthalene-1-carbonyl]amino]-2,4-dimethyl-benzoic acid.

12 . A method of treating osteoarthritis in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound, or pharmaceutically acceptable salt thereof, according to claim 1 .

13 . A method of treating rheumatoid arthritis in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound or pharmaceutically acceptable salt thereof, according to claim 1 .

14 . A method of treating pain associated with osteoarthritis or rheumatoid arthritis in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound or a pharmaceutically acceptable salt thereof, according to claim 1 .

15 . (canceled)

16 . (canceled)

17 . (canceled)

18 . (canceled)

19 . A pharmaceutical composition, comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients.

Assignees

• Lilly Co Eli

Inventors

• Blanco-Pillado Maria Jesus
• Manninen Peter Rudolph
• Schiffler Matthew Allen
• Vetman Tatiana Natali
• Warshawsky Alan M
• York Jeremy Schulenburg

Classifications

• A61P29/00

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D215/52

  with aryl radicals attached in position 2 · CPC title