PPARδ activator

Patent metadata

Field	Value
Publication number	US-12268672-B2
Application number	US-201917286904-A
Country	US
Kind code	B2
Filing date	Oct 23, 2019
Priority date	Oct 23, 2018
Publication date	Apr 8, 2025
Grant date	Apr 8, 2025

Abstract

The present invention provides a PPARδ activator containing a novel PPARδ agonist (peroxisome proliferator-activated receptor δ) as an active ingredient, and an exercise tolerance-improving agent containing the same as an active ingredient. The present invention is a PPARδ activator containing a guanidine derivative or a biguanidine derivative as an active ingredient, wherein the PPARδ activator activates transcriptional activity of PPARδ, and the guanidine derivative and the biguanidine derivative are capable of fitting within a PPARδ ligand binding pocket in a state where a guanidino group or a biguanidino group forms a hydrogen bond with amino acid residues corresponding to each of the 413th histidine, 287th histidine, 253rd threonine and the 437th tyrosine of human PPARδ, among amino acid residues constituting an interior surface of the ligand binding pocket; and is an exercise tolerance-improving agent containing the PPARδ activator as an active ingredient.

First claim

The invention claimed is:

1. A PPARδ agonist comprising a guanidine derivative as an active ingredient, wherein
the PPARδ agonist activates transcriptional activity of PPARδ (peroxisome proliferator-activated receptor δ); and
the guanidine derivative is a compound represented by any of the following formulas (A-1) to (A-4), (B-1) to (B-3),

2. The PPARδ agonist according to claim 1 , wherein
the guanidine derivative is capable of fitting within a ligand binding pocket of PPARδ, in a state where a guanidino group form a hydrogen bond with amino acid residues corresponding to each of the 413th histidine, 287th histidine, 253rd threonine and the 437th tyrosine of human PPARδ, among amino acid residues constituting an interior surface of the ligand binding pocket.

3. An exercise tolerance-improving agent comprising the PPARδ agonist defined in claim 1 as an active ingredient.

4. A pharmaceutical composition containing the PPARδ agonist according to claim 1 , wherein
the pharmaceutical composition is for treating or preventing a disease for which a therapeutic effect can be obtained by activating a transcriptional activity of PPARδ.

5. The pharmaceutical composition according to claim 4 , wherein the disease is diabetes, obesity, cardiomyopathy, or liver fibrosis.

6. The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is for immunotherapy.

Assignees

• Japan Science & Tech Agency

Inventors

• Ogura Toshihiko
• Hakoshima Toshio
• MIYASAKA Kota
• Kubo Atsushi

Classifications

• A61K31/155

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• A61P43/00

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

• C07C2601/14

  The ring being saturated · CPC title

• C07C279/08

  being further substituted by singly-bound oxygen atoms · CPC title

• C07D277/26

  Radicals substituted by sulfur atoms · CPC title