Prostaglandin E synthase inhibitors and methods for utilizing the same

Patent metadata

Field	Value
Publication number	US-11325901-B2
Application number	US-201716305386-A
Country	US
Kind code	B2
Filing date	Jun 28, 2017
Priority date	Jun 28, 2016
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

Compounds and compositions are provided that can inhibit microsomal prostaglandin E synthase-1 (mPGES-1). The compounds and compositions can reduce inflammation in a subject, such as inflammation caused by an inflammation disorder or symptoms thereof. Pharmaceutical compositions comprising the compound are also provided. Furthermore, methods are provided for reducing inflammation and/or inhibiting mPGES-1. The methods can comprise administering an effective amount of the composition to a subject.

First claim

What is claimed is:

1. A compound of the formula:

or pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of H, halide, Me, OMe, OEt, NO 2 , OH, and, together with the ring to which it is attached, a bicyclic ring system;
wherein R 2 is alkyl and includes more than one alkyl-carbons, and wherein the R 2 alkyl is not substituted for carboxylic acid;
wherein R 3 is selected from the group consisting of H and Me; and
wherein X is selected from the group consisting of O or S.

2. The compound of claim 1 , wherein R 1 is selected from the group consisting of: H, Cl, Br, I, Me, OMe, OEt, NO 2 , OH, and, taken together with the ring to which it is attached, a bicyclic ring system; and/or wherein R 2 is selected from the group consisting of:

3. The compound of claim 1 , having the formula selected from the group consisting of:

4. The compound of claim 1 , wherein R 1 is selected from the group consisting of:
H,

and/or
R 2 is selected from the group consisting of:

H,

and/or
wherein R 3 is selected from the group consisting of:
H,

5. The compound of claim 1 , wherein R is selected from the group consisting of:

6. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically-acceptable carrier.

7. The pharmaceutical composition of claim 6 , further comprising: a second compound or composition having mPGES-1 inhibition activity, having anti-inflammatory activity, being useful for treatment of an inflammation disorder, being useful for treatment of symptoms associated inflammation and/or an inflammation disorder, or combinations thereof.

8. A method of reducing inflammation in a subject, comprising administering to the subject an effective amount of a compound of claim 1 .

9. The method of claim 8 , wherein the subject includes an inflammation disorder or symptoms thereof.

10. The method of claim 9 , wherein the inflammation disorder is selected from the group consisting of inflammation, arthritis, fever, pain, cancer, stroke, bone disorders, and combinations thereof.

11. The method of claim 8 , wherein the compound inhibits microsomal prostaglandin E synthase-1 (mPGES-1).

12. A compound of the formula:

or pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of H, halide, Me, OMe, OEt, NO 2 , OH, and, together with the ring to which it is attached, a bicyclic ring system;
wherein R 3 is selected from the group consisting of H and Me;
wherein X is selected from the group consisting of O or S; and
wherein R 2 is selected from the group consisting of:

13. A compound of the formula:

or pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of H, halide, Me, OMe, OEt, NO 2 , OH, and, together with the ring to which it is attached, a bicyclic ring system;
wherein R 2 is alkyl;
wherein R 3 is selected from the group consisting of H and Me;
wherein X is selected from the group consisting of O or S; and
wherein the compound has a formula selected from the group consisting of:

14. A method of reducing inflammation in a subject, comprising administering to the subject an effective amount of a compound of the formula:

or pharmaceutically acceptable salts thereof;
wherein R 1 is selected from the group consisting of H, halide, Me, OMe, OEt, NO 2 , OH, and, together with the ring to which it is attached, a bicyclic ring system;
wherein R 2 is alkyl;
wherein R 3 is selected from the group consisting of H and Me;
wherein X is selected from the group consisting of O or S; and
wherein the compound inhibits microsomal prostaglandin E synthase-1 (mPGES-1).

Assignees

• Univ Kentucky Res Found

Inventors

• Zhan Chang-Guo
• Zheng Fang
• Ding Kai
• Zhou Ziyuan

Classifications

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D277/34 Primary

  Oxygen atoms · CPC title

• C07C255/37

  the carbon skeleton being further substituted by etherified hydroxy groups · CPC title

• C07D251/20

  with no nitrogen atoms directly attached to a ring carbon atom · CPC title

• C07C205/32

  having nitro groups bound to acyclic carbon atoms and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton · CPC title