γ-diketones as Wnt/β-catenin signaling pathway activators

Patent metadata

Field	Value
Publication number	US-10457672-B2
Application number	US-201815918086-A
Country	US
Kind code	B2
Filing date	Mar 12, 2018
Priority date	Feb 22, 2013
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.

First claim

What is claimed is:

1. A compound of Formula IIIb:

or a pharmaceutically acceptable salt thereof,
wherein:
R 14 is selected from the group consisting of unsubstituted —C 1-6 alkyl, —C 1-3 haloalkyl, and CF 3 ;
R 15 is selected from the group consisting of unsubstituted —C 1-6 alkyl, —C 1-3 haloalkyl, and CF 3 ;
each R 16 is independently selected at each occurrence from the group consisting of H, unsubstituted —C 1-6 alkyl, —CH 2 OH, —CH 2 N(R 17b ) 2 , —C 1-3 haloalkyl, halide, —OR 17 , CF 3 , and CN;
each R 17 is independently selected from the group consisting of unsubstituted —C 1-6 alkyl, —C 1-3 haloalkyl, and CF 3 ;
each R 17b is independently selected from the group consisting of H and unsubstituted —C 1-3 alkyl; and
q is an integer of 1 to 5;
with the proviso that the compound of Formula IIIb is not a compound selected from the group consisting of:

2. The compound of claim 1 , wherein R 14 and R 15 are independently selected from the group consisting of CH 3 and CF 3 .

3. The compound of claim 2 , wherein R 14 and R 15 are both CH 3 .

4. The compound of claim 1 , wherein each R 16 is independently selected at each occurrence from the group consisting of H, Me, halide, —OMe, CF 3 , and CN.

5. The compound of claim 3 , wherein each R 16 is independently selected at each occurrence from the group consisting of H, Me, halide, —OMe, CF 3 , and CN.

6. The compound of claim 5 , wherein R 16 is independently selected at each occurrence from the group consisting of H, Me, halide, —OMe, CF 3 , and CN; and q is 1.

7. The compound of claim 5 , wherein R 16 is independently selected at each occurrence from the group consisting of H, Me, F, and Cl; and q is 1.

8. The compound of claim 1 , wherein the compound of Formula IIIb is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

Assignees

• Samumed Llc

Inventors

• Kc Sunil Kumar
• Wallace David Mark
• Hood John
• Barroga Charlene F

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D327/06

  Six-membered rings · CPC title

• C07D213/50

  Ketonic radicals · CPC title

• C07D263/56

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2 · CPC title

• C07D317/54

  Radicals substituted by oxygen atoms · CPC title