Krüppel-like factor 15 (KLF15) small molecule agonists in kidney disease

Patent metadata

Field	Value
Publication number	US-11643394-B2
Application number	US-202117244762-A
Country	US
Kind code	B2
Filing date	Apr 29, 2021
Priority date	Apr 30, 2020
Publication date	May 9, 2023
Grant date	May 9, 2023

Abstract

The present disclosure is concerned with small molecule modulators of KLF15 signaling useful for treating various disorders such as, for example, kidney disease (e.g., chronic kidney disease), heart disease, obesity, or a neurodegenerative disorder (e.g., amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, spinal muscular atrophy, traumatic brain injury, vascular dementia, Huntington's disease, mental retardation, and attention deficit and hyperactivity disorder (ADHD)). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A compound having a structure represented by a formula:

wherein each of Q 1 and Q 2 , when present, is independently selected from N and CR 10 ;
wherein R 10 , when present, is selected from hydrogen and halogen;

wherein Z 1 is selected from N and CR 2b ;
wherein Z 2 is selected from N and CR 2c ;
wherein R 1 is C1-C4 alkyl;
wherein each of R 2a , R 2b , R 2c , R 2d , R 3a , and R 3b , when present, is independently selected from hydrogen and halogen;
wherein R 4 is selected from halogen, —CN, —OH, C1-C4 alkyl, C1-C4 alkoxy, —B(R 12 ) 3 , and a structure:

substituted with 0, 1, 2, 3, or 4 C1-C4 alkyl groups;
wherein each occurrence of R 12 , when present, is independently halogen,
provided that when the compound has a structure represented by a formula:

then R 4 is a structure:

substituted with 0, 1, 2, 3, or 4 C1-C4 alkyl groups, and
provided that when the compound has a structure represented by a formula:

then R 4 is not halogen,
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 4 is selected from halogen, —CN, —OH, C1-C4 alkyl, C1-C4 alkoxy, and a structure:

substituted with 0, 1, 2, 3, or 4 C1-C4 alkyl groups.

3. The compound of claim 1 , wherein R 1 is methyl.

4. The compound of claim 1 , wherein each of R 2a , R 2b , R 2c , R 2d , R 3a , and R 3b is hydrogen.

5. The compound of claim 1 , wherein the compound has a structure represented by a formula:

6. The compound of claim 5 , wherein one of Q 1 and Q 2 is CH and one of Q 1 and Q 2 is N.

7. The compound of claim 5 , wherein the compound has a structure represented by a formula:

8. The compound of claim 5 , wherein the compound is selected from:

9. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , and a pharmaceutically acceptable carrier.

Assignees

• Us Gov Veterans Affairs
• Icahn School Med Mount Sinai
• Univ New York State Res Found
• Us Gov Veterans Affairs

Inventors

• Mallipattu Sandeep
• Das Bhaskar

Classifications

• A61K31/573 Primary

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title